bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate
Authors: Najafi Sahar , Ghanavat Majid , Shahrabi Saied , Gatavizadeh Zahra , Saki Najmaldin
Published: January 2021

Inflammatory cytokines exert different effects on hematopoietic stem cells (HSCs), lead to the development of various cell lineages in bone marrow (BM) and are thus a differentiation axis for HSCs. The content used in this article has been obtained by searching PubMed database and Google Scholar search engine of English‐language articles (1995–2020) using “Hematopoietic stem cell,” “Inflammatory cytokine,” “Homeostasis,” and “Myelopoiesis.” Inflammatory cytokines are involved in the differentiation and proliferation of hematopoietic progenitors to compensate for cellular death due to inflammation. Since each of these cytokines differentiates HSCs into a specific cell line, the difference in the effect of these cytokines on the fate of HSC progenitors can be predicted. Inhibitors of these cytokines can also control the inflammatory process as well as the cells involved in leukemic conditions. In general, inflammatory signaling can specify the dominant cell line in BM to counteract inflammation and leukemic condition via stimulating or inhibiting hematopoietic progenitors. Therefore, detection of the effects of inflammatory cytokines on the differentiation of HSCs can be an appropriate approach to check inflammatory and leukemic conditions and the suppression of these cytokines by their inhibitors allows for control of homeostasis in stressful conditions.
Utilization of moderate pressure and elevated temperatures in the optimization of Ti2AlC‐cBN composites using SPS technique
Authors: Rampai Tokoloho , Sigalas Iakovos , Whitefield David
Published: January 2021

The formation reaction mechanism of Ti2AlC cubic boron nitride (cBN) composite materials was investigated using different particle sizes at different volume percentages of cBN (20 and 40 vol%), at a constant moderate pressure while varying time and temperature. The results show that, under the investigated conditions, Ti2AlC decomposed at 1300°C with a simultaneous hexagonalization of the cBN, resulting in the creation of secondary phases including TiB2, TiC, TiN and AlN. It was observed that the optimum time and temperature for fabricating Ti2AlC‐cBN composites, where both phases were abundantly present, was 1250°C for 5 minutes for all composites. Under these conditions, there was no hBN in the resulting composites. Increasing the average particle size of cBN powder enhanced the stability of the Ti2AlC and cBN in the samples. Also, the increase in volume fraction of cBN was observed to further promote the stability of Ti2AlC and cBN in the samples. This was due to the decrease in surface area of cBN, which hampered hexagonalization of cBN. Whatever excess hBN present reacted completely with the MAX phase in the final composites. The secondary phases formed in the samples were TiAl2, Ti3Al, TiCb, TiB2, TiCxNy (in samples containing 100 µm cBN) and TiN (in samples containing 20 vol.% cBN). The reaction area between Ti2AlC and cBN was strongly bonded to the cBN and Ti2AlC phases. A controlled method of simultaneous hexagonalization of cBN and reaction of the resultant hBN with Ti2AlC has proved superior in forming composites of Ti2AlC with cBN.
Single‐Atom Alloys for the Electrochemical Oxygen Reduction Reaction
Authors: Darby Matthew T. , Stamatakis Michail
Published: January 2021

Single‐atom alloys (SAAs) consisting of isolated transition‐metal atoms doped in the surface of coinage metal hosts exhibit unique catalytic properties, harnessing the high activity of the dopant metals with the selectivity of the coinage metal hosts. Here we use density functional theory (DFT) to study SAAs comprised of Ni, Pd, Pt, Co and Rh doped into Ag and Au hosts, as candidate electrocatalysts for the oxygen reduction reaction (ORR) in proton‐exchange membrane (PEM) fuel‐cells. Our calculations reveal that the PdAu SAA exhibits a slightly lower theoretical overpotential, enhanced selectivity for 4‐e− ORR, and tolerance to CO‐poisoning compared to Pt(111). While the number of active sites of PdAu SAA is lower than that of Pt(111), the aforementioned desirable properties could bring the overall catalytic performance thereof close to that of Pt/C, indicating that the PdAu SAA could be a viable material for electrocatalytic ORR in PEM fuel‐cells.
External correlates of the SPECTRA: Indices of psychopathology (SPECTRA) in a clinical sample
Authors: Blais Mark A. , Sinclair Samuel Justin , Richardson Laura A. , Massey Christina , Stein Michelle B.
Published: January 2021

The SPECTRA: Indices of Psychopathology is a broadband assessment inventory compatible with contemporary hierarchical models of psychopathology (internalizing, externalizing, reality impairing dimensions and global psychopathology factor). This study explored the SPECTRA's construct validity using a wide range of life event (extra‐test) variables in a clinical sample. The life event variables included the following: education level, school failure, childhood adversity, suicide attempts, psychiatric hospitalizations, depression, psychotic symptoms, self‐injury, substance abuse, arrests, physical violence, marital status, employment status and current medications. Results showed that all SPECTRA clinical scales had significant life event correlations. For the higher‐order Spectra scales, the global index of psychopathology had the greatest number and range of life event correlations. Correlations for the externalizing and reality impairing Spectra scales provided solid validity evidence, while correlations for the internalizing Spectra scale were more diffuse. These findings provide the first non‐test‐based evidence of construct validity for the SPECTRA.
Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy
Authors: Crews Kristine R. , Monte Andrew A. , Huddart Rachel , Caudle Kelly E. , Kharasch Evan D. , Gaedigk Andrea , Dunnenberger Henry M. , Leeder J. Steven , Callaghan John T. , Samer Caroline Flora , Klein Teri E. , Haidar Cyrine E. , Van Driest Sara L. , Ruano Gualberto , Sangkuhl Katrin , Cavallari Larisa H. , Müller Daniel J. , Prows Cynthia A. , Nagy Mohamed , Somogyi Andrew A. , Skaar Todd C.
Published: January 2021

Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes that have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol‐O‐methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1, and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone, and methadone, and for OPRM1 and COMT for clinical use.
Redox Potential Heterogeneity in Fixed‐Bed Electrodes Leads to Microbial Stratification and Inhomogeneous Performance
Authors: Quejigo Jose Rodrigo , Korth Benjamin , Kuchenbuch Anne , Harnisch Falk
Published: January 2021

Bed electrodes provide high electrode area‐to‐volume ratios represent a promising configuration for transferring bioelectrochemical systems close to industrial applications. Nevertheless, the intrinsic electrical resistance leads to poor polarization behavior. Therefore, the distribution of Geobacter spp. and their electrochemical performance within exemplary fixed‐bed electrodes are investigated. A minimally invasive sampling system allows characterization of granules from different spatial locations of bed electrodes. Cyclic voltammetry of single granules (n=63) demonstrates that the major share of electroactivity (134.3 mA L−1) is achieved by approximately 10 % of the bed volume, specifically that being close to the current collector. Nevertheless, analysis of the microbial community reveals that Geobacter spp. dominated all sampled granules. These findings clearly demonstrate the need for engineered bed electrodes to improve electron exchange between microorganisms and granules.
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

In 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

Background

As 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.

Methods

We 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).

Results

We 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.

Conclusions

Our 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

Clonal 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

Living 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

Background

Cell‐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.

Results

Changes 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.

Conclusions

These 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

Debris 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

Objectives

Early 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.

Methods

We 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.

Results

We 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).

Conclusions

OCT 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

Objectives

To 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.

Methods

A 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.).

Results

Twenty‐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.

Conclusion

Pediatric 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

Market 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

Breast 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

The 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

Background

Lipoprotein 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).

Methods

A 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.

Results

The 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).

Conclusions

The 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

Nadolol 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.
Uncovering temperature‐dependent extracellular vesicle secretion in breast cancer
Authors: Otsuka Kurataka , Yamamoto Yusuke , Ochiya Takahiro
Published: January 2021

In all living things, temperature is a key factor to maintain function and survive. Animals and plants need to adapt temperature change with optimizing their behaviour and growth by sensing temperature. Similarly, tumour cells must adapt continuously to fluctuations in external conditions including temperature. To find a better environment, cancer cells promote growth and metastasis, which contributes to tumour malignancy. Pathological studies in breast cancer have implied that temperature is associated with disease progression. However, no clear mechanisms have emerged for how thermal changes affect tumour cells and their gene regulation in tumour development and malignancy. Here we discovered the temperature‐dependent extracellular vesicle (EV) secretion in breast cancer. Cancer cell growth and EV secretion increased in a temperature‐dependent manner, which indicated that temperatures were associated with poor prognosis in breast cancer patients. We also found that low‐density lipoprotein receptor (LDLR), a responsible gene for temperature‐dependent EV secretion, was upregulated with the increase in temperature. Consistent with our results, LDLR gene has been characterized and identified as a key factor for malignancy in a wide range of cancers. Our findings shed new light on tumour aggressiveness and therapeutic strategies for breast cancer, especially regarding EV formation and secretion, thus providing a new relationship between cancer and EV biology in the light of temperature.
Pre‐instrumental summer precipitation variability in northwestern Greece from a high‐elevation Pinus heldreichii network
Authors: Esper Jan , Konter Oliver , Klippel Lara , Krusic Paul J. , Büntgen Ulf
Published: January 2021

The spatiotemporal variability of precipitation is of vital importance to Mediterranean ecology and economy, but pre‐instrumental changes are not well understood. Here, we present a millennial‐length June–July precipitation reconstruction derived from a network of 22 Pinus heldreichii high‐elevation sites in the Pindus Mountains of northwestern Greece. Tree‐ring width chronologies from these sites cohere exceptionally well over the past several hundred years (r1467–2015 = 0.64) revealing coherence at inter‐annual to centennial timescales across the network. The network mean calibrates significantly against instrumental June–July precipitation over the past 40 years (r1976–2015 = 0.71), even though no high‐elevation observational record is available representing the moist conditions at the treeline above 1,900 m a.s.l. For the final reconstruction, the instrumental target data are adjusted to provide realistic estimates of high‐elevation summer rainfall back to 729 CE. The reconstruction contains substantially more low‐frequency variability than other high‐resolution hydroclimate records from the eastern Mediterranean including extended dry periods from 1,350 to 1,379 CE (39 ± 4.5 mm) and 913 to 942 (40 ± 8.4 mm), and moist periods from 862 to 891 (86 ± 11 mm) and 1,522 to 1,551 (80 ± 3.5 mm), relative to the long‐term mean of 61 mm. The most recent 30‐year period from 1986 to 2015 is characterized by above average June–July precipitation (73 ± 2 mm). Low‐frequency changes in summer precipitation are likely related to variations in the position and persistence of storm tracks steering local depressions and causing extensive rainfall (or lack thereof) in high‐elevation environments of the Pindus Mountains.
Effect of individual and neighborhood social capital on gingival bleeding in children: A 7‐year cohort study
Authors: Ferreira Danielle Martins , Knorst Jessica Klöckner , Menegazzo Gabriele Rissotto , Bolsson Gabriela Bohrer , Ardenghi Thiago Machado
Published: January 2021

Background

Social capital incorporates contextual and individual levels of interactions, which influence human health. The aim of this study was to evaluate the influence of individual and contextual social capital in early childhood on gingival bleeding in children after 7 years.

Methods

This 7‐year cohort study was conducted with a randomized sample of 639 children (1 to 5 years old) evaluated in 2010 (T1) in Santa Maria, southern Brazil. Gingival bleeding was recorded during follow‐up (T2). Contextual (social class association and number of churches) and individual (religious practice, volunteer networks, and school involvement) social capital variables were collected at baseline, along with demographic, socioeconomic, and oral health variables. A multilevel Poisson regression model was used to investigate the influence of individual and contextual variables on mean gingival bleeding. The incidence rate ratio (IRR) and 95% confidence interval (95% CI) were calculated.

Results

A total of 449 children were reassessed after 7 years (70.3% cohort retention rate). Children living in areas with a larger number of churches at baseline had lower mean gingival bleeding at follow‐up. Regarding individual social capital, children whose parents did not attend school activities were more likely to have gingival bleeding. Additionally, low maternal education, poor parents’ perception of oral health, non‐use of dental services, and low frequency of tooth brushing were related to higher mean gingival bleeding at follow‐up.

Conclusion

The presence of more churches in neighborhoods and parents' involvement in a child's school activities positively influenced children's oral health, and these individuals had lower mean gingival bleeding.
Subgingival microbiota in overweight and obese young adults with no destructive periodontal disease
Authors: de Andrade Danielle Rodrigues , Silva Paulo André , Colombo Ana Paula V. , Silva‐Boghossian Carina Maciel
Published: January 2021

Background

This study analyzed the levels of a specific group of periodontal health/disease‐related oral bacteria in the subgingival biofilm of young adults with overweight (OW) and obesity (OB), and no destructive periodontal disease.

Methods

Full‐mouth periodontal assessment and subgingival biofilm sampling were performed in individuals with normal weight (NW) (BMI [body mass index] ≥18.5 to ≤24.9 kg/m2; n = 29), OW (BMI ≥25 to ≤29.9 kg/m2; n = 26), or OB (BMI ≥30 kg/m2; n = 22). BMI, waist (WC) and hip (HC) circumferences, and waist‐hip ratio (WHR) were established for every individual. Biofilm samples were analyzed by checkerboard. Spearman coefficient, linear, and logistic regression analyses were obtained.

Results

Gingivitis was detected in 45% NW, 65% OW, and 73% OB individuals. NW patients presented significantly less calculus and supragingival biofilm than OB. OW, and OB individuals had significantly higher levels of Porphyromonas gingivalis and Tannerella forsythia than NW patients (P <0.05). Treponema denticola correlated with BMI (rho = 0.31), WC (rho = 0.28), and HC (rho = 0.29), P≤0.01. Linear regression analysis showed significant (P <0.05) positive associations between BMI, WC, HC, and WHR indicators and Prevotella spp., Lactobacillus spp., V. parvula, and A. actinomycetemcomitans (Aa); negative associations were found between Capnocytophaga spp., WC, and HC (β = −0.29 and β = −0.37, respectively; P <0.01). However, the interaction of Prevotella spp. and T. forsythia decreased the likelihood of an individual to be diagnosed as OW/OB (OR 0.183 [95% CI, 0.062–0.540]).

Conclusions

Few periodontal pathogens differed in levels between NW and OW/OB individuals without destructive periodontal disease. Moreover, Aa, T. denticola, and Prevotella spp. were associated with clinical parameters of obesity.
Facial mucosal level of single immediately placed implants with either immediate provisionalization or delayed restoration: An intermediate‐term study
Authors: Bushahri Ali , Kripfgans Oliver D. , George Furat , Wang I‐Ching , Wang Hom‐Lay , Chan Hsun‐Liang
Published: January 2021

Background

Immediately placed single implants with either immediate provisionalization (test) or delayed restoration (control) were followed for up to 1 year in our previous randomized clinical trial. Peri‐implant tissues continue to remodel after implants are in function. Therefore, the primary aim of this study was to evaluate the facial mucosal level changes in the intermediate term between the two groups and to study potential factors influencing the mucosal level change.

Methods

Patients who had already completed the previous clinical trial by receiving a single immediately placed implant were re‐invited to this study. The facial mucosal level as well as the other peri‐implant hard and soft tissue dimensions and conditions were measured clinically, radiographically and with ultrasound. These data were compared between the test and control implants. The mucosal level change as the function of the final crown contour, measured as the abutment‐crown angle (ACA), was estimated with a linear regression model.

Results

Twenty‐eight patients (n of test/control = 16/12) with a mean 30‐month follow‐up were recruited. The mean mucosal level change was ‐0.38 mm (control) and 0.06 mm (test), without statistical difference between the two groups. The other clinical, radiographic, and ultrasound parameters were not statistically different. ACA was statistically significant associated with the recession (P = 0.02). The estimate effect was 0.25 mm per 10° increase (adjusted R2 = 0.18; 95% CI, 0.02 to 0.49 mm). After adjusting for vertical implant position, implant abutment angle and the group, the effect became borderline significant (P = 0.09).

Conclusions

Peri‐implant tissues, including the mucosal level change of immediately placed implants with either immediate provisionalization or delayed restoration remained stable and did not differ between the groups in the intermediate term. The final crown angle, influenced by implant position and abutment angle, might be associated with mucosal margin level change.
Simultaneous quantification of arctigenin and its glucuronide conjugate in mouse plasma using ultra‐high performance liquid chromatography coupled to tandem mass spectrometry
Authors: Suzuki Yosuke , Sato Michiko , Awazuhara Takuya , Nukui Yusuke , Yoshida Airi , Terashima Tomoka , Watanabe Keita , Fujioka Rumi , Tsuchihara Katsuya , Kishino Satoshi , Ohno Keiko
Published: January 2021

Arctigenin is a natural lignin and a main active component of Fructus arctii, the dried fruit of Arctium lappa. This compound was reported to have some biological activities such as anti‐inflammatory, antioxidant, antiviral, renoprotective, and antitumor effects. Arctigenin is mainly metabolized to arctigenin‐4′‐O‐glucuronide by UDP‐glucuronosyltransferase. In this study, a simultaneous quantification method was established and validated for measuring arctigenin and arctigenin‐4′‐O‐glucuronide in mouse plasma using ultra‐high performance liquid chromatography with tandem mass spectrometry. The assay fulfilled the requirements of the United States Food and Drug Administration guideline for assay validation, with a lower limit of quantification of 2.00 ng/mL for arctigenin and 50.0 ng/mL for arctigenin‐4′‐O‐glucuronide. The recovery rate and matrix effect ranged from 78.4 to 102.8% and 92.5 to 106.3%, respectively, for arctigenin, and 74.3 to 109.2% and 94.9 to 110.2% for arctigenin‐4′‐O‐glucuronide. The method was applied to the measurement of plasma concentrations of arctigenin and arctigenin‐4′‐O‐glucuronide in the plasma of mice after administration of arctigenin. All measured concentrations were within the calibration ranges. Our novel method may be useful to measure plasma arctigenin and arctigenin‐4′‐O‐glucuronide concentrations, and contribute to evaluate the pharmacokinetics of arctigenin and arctigenin‐4′‐O‐glucuronide in mice.
Bagley polygon power divider realized by ridge gap waveguide technology
Authors: Karimi Nobandegani Abbas , Hosseini S. Esmail
Published: January 2021

The novel ridge‐gap waveguide (RGW) technology which uses a full metal structure has many advantages in micro/mm‐wave frequencies such as low loss, broad bandwidth, low sensitivity to manufacturing errors, and easy integration with active components, and so forth. In this paper, a Ku‐band 3‐way Bagley polygon power divider (BPD) is proposed and experimentally demonstrated based on the RGW technology for the first time, to the best of our knowledge. An RGW‐toWR62 transition is also designed and fabricated. The proposed three‐way RGW‐based BPD with WR62 transitions shows low‐loss equal‐power division in phase with good impedance matching and isolation between output ports in the Ku band. The proposed RGW‐based BPD can be extended to an N‐way power divider.
Concept of vertical liquid metal actuated cyclo‐olefin‐polymer based embedded 360° steerable Yagi‐Uda antenna
Authors: Le Goff Denis , Quéré Yves , Maalouf Azar , Rius Eric , Coquet Philippe , Teo Edwin Hang Tong
Published: January 2021

The concept of a reconfigurable 5GHz microfluidically actuated antenna with beam forming, steering and hoping in a 360° angular range, is presented in this paper. Its architecture is that of a Yagi‐Uda array. Its actuation relies on the electrically controlled vertical displacement of liquid metal slugs inside microfluidic channels without the need of any external actuator. Simulations results along two fabricated proofs of concept investigating RF and microfluidic actuation performances are presented. This paper aims at demonstrating the technical soundness and interest of this design for applications such as autonomous sensors networks.
Task group 284 report: magnetic resonance imaging simulation in radiotherapy: considerations for clinical implementation, optimization, and quality assurance
Authors: Glide‐Hurst Carri K. , Paulson Eric S. , McGee Kiaran , Tyagi Neelam , Hu Yanle , Balter James , Bayouth John
Published: January 2021

The use of dedicated magnetic resonance simulation (MR‐SIM) platforms in Radiation Oncology has expanded rapidly, introducing new equipment and functionality with the overall goal of improving the accuracy of radiation treatment planning. However, this emerging technology presents a new set of challenges that need to be addressed for safe and effective MR‐SIM implementation. The major objectives of this report are to provide recommendations for commercially available MR simulators, including initial equipment selection, siting, acceptance testing, quality assurance, optimization of dedicated radiation therapy specific MR‐SIM workflows, patient‐specific considerations, safety, and staffing. Major contributions include guidance on motion and distortion management as well as MRI coil configurations to accommodate patients immobilized in the treatment position. Examples of optimized protocols and checklists for QA programs are provided. While the recommendations provided here are minimum requirements, emerging areas and unmet needs are also highlighted for future development.