bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphometric analysis of shape differences in Windover and Point Hope archaic human mandibles
Authors: Boren Seth , Slice Dennis , Thomas Geoffrey
Published: October 2018

Objectives

The mandible can provide valuable information on both the life history and genetic makeup of Archaic human populations. The following analysis tests two hypotheses: (a) that there are significant differences in morphology in mandibular shape between the genders amongst Archaic North American Homo sapiens and (b) that there is a significant difference in variance in mandibular shape between Archaic Windover and Point Hope.

Materials and Methods

A sample made from mandible specimens taken from both populations is subjected to Principal Component Analyses (PCA). The component scores from the PCAs are subjected to both a Multivariate Analysis of Covariance (mancova) and a general Multivariate Analysis of Variance (manova) to determine whether significant differences in variance exist between the sexes and the populations.

Results

The mancova found that there are no significant interactions between the PC scores in population, sex, or size. Significant differences in variance were found between males and females and between the Windover and Point Hope populations.

Conclusions

Differences in variance observed between the populations are suspected to be due to differences in subsistence strategies and possibly non‐masticatory utilizations of teeth. Differences in variance between the genders are suspected to be genetic in origin.
Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage
Authors: Sugimoto Kazutaka , Nomura Sadahiro , Shirao Satoshi , Inoue Takao , Ishihara Hideyuki , Kawano Reo , Kawano Akiko , Oka Fumiaki , Suehiro Eiichi , Sadahiro Hirokazu , Shinoyama Mizuya , Oku Takayuki , Maruta Yuichi , Hirayama Yuya , Hiyoshi Koichiro , Kiyohira Miwa , Yoneda Hiroshi , Okazaki Koki , Dreier Jens P. , Suzuki Michiyasu
Published: October 2018

Objective

Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs.

Methods

Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n = 23) or control group (n = 27). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD‐induced perfusion deficits (spreading ischemia) was assessed in an aSAH‐mimicking model.

Results

There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio = 0.266, 95% confidence interval [CI] = 0.059–1.192, p = 0.084). However, the total SD‐induced depression duration per recording day (22.2 vs 30.2 minutes, β = −251.905, 95% CI = −488.458 to −15.356, p = 0.043) and the occurrence of isoelectric SDs (0 vs 4 patients, β = −0.916, 95% CI = −1.746 to −0.085, p = 0.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD‐induced spreading ischemia compared to vehicle (Student t test, difference = 30.2, 95% CI = 5.3–55.1, p = 0.020).

Interpretation

Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH‐mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018;84:873–885
Germanium Wafers Possessing Facet‐Dependent Electrical Conductivity Properties
Authors: Hsieh Pei‐Lun , Lee An‐Ting , Chen Lih‐Juann , Huang Michael H.
Published: October 2018

Electrical conductivity properties of Ge {100}, {110}, {111}, and {211} facets have been measured by breaking Ge (100) and (111) wafers to expose {110} and {211} surfaces and contacting the different facets with tungsten probes. Ge {111} and {211} faces are far more conductive than the already conductive Ge {100} and {110} faces, matching with recent density functional theory (DFT) predictions. Asymmetric I–V curves resembling those of p‐n junctions have been collected for the {110}/{111} and {110}/{211} facet combinations. The current‐rectifying effects stem from different degrees of surface band bending for the highly and less conductive faces and the direction of current flow. This work demonstrates that germanium wafers also possess facet‐dependent electrical conductivity responses that can be utilized in the fabrication of novel fin field‐effect transistors (finFET).
Bimetallic Rhodium(II)/Indium(III) Relay Catalysis for Tandem Insertion/Asymmetric Claisen Rearrangement
Authors: Chen Yushuang , Dong Shunxi , Xu Xi , Liu Xiaohua , Feng Xiaoming
Published: October 2018

The first example of catalytic insertion/asymmetric Claisen rearrangement tandem reaction of N‐sulfonyl‐1,2,3‐triazoles with allyl alcohol esters was achieved by bimetallic relay catalytic systems involving achiral rhodium salt and chiral N,N′‐dioxide–indium(III) complex. This manifold could overcome the limitation of single RhII catalysis, providing a straight and facile route to various enantioenriched β/γ‐amino acid derivatives in high yields (up to 99 %) with excellent diastereo‐ and enantioselectivities (up to >95:5 dr, 98:2 er). Moreover, possible transition state models were proposed to elucidate the origin of chiral induction based on the control experiments and X‐ray crystal structure of the catalyst.
Creating Elastic Organic Crystals of π‐Conjugated Molecules with Bending Mechanofluorochromism and Flexible Optical Waveguide
Authors: Hayashi Shotaro , Yamamoto Shun‐ya , Takeuchi Daisuke , Ie Yutaka , Takagi Koji
Published: October 2018

To create low band‐gap, fluorescent, and elastic organic crystal emitters, we focused on an extended π‐conjugated system based on: a) a planar conformation,b) a rigid structure, and c) controlled intermolecular interactions. Herein, we report on two fluorescent and highly flexible organic crystals (1 and 2) which could bend under an applied stress. The bent crystals rapidly recover their straight shape upon release of the stress. Crystal 1 with a tetrafluoropyridyl terminal unit and a lower band‐gap energy (orange emission, λem=573 nm, ΦF=0.50), showed no bending mechanofluorochromism and had superior performance as an optical waveguide with reddish orange emission. The waveguide performance of the crystal did not decrease under bending stress. For crystal 2 with a pentafluorophenyl terminal unit (green emission, λem=500 nm, ΦF=0.38), the original waveguide performance decreased under an applied bending stress; however, this crystal showed a unique bending mechanofluorochromism.
Regulating Cofactor Balance In Vivo with a Synthetic Flavin Analogue
Authors: Tan Zhuotao , Zhu Chenjie , Fu Jingwen , Zhang Xiaowang , Li Ming , Zhuang Wei , Ying Hanjie
Published: October 2018

A novel strategy to regulate cofactor balance in vivo for whole‐cell biotransformation using a synthetic flavin analogue is reported. High efficiency, easy operation, and good applicability were observed for this system. Confocal laser scanning microscopy was employed to verify that the synthetic flavin analogue can directly permeate into Escherichia coli cells without modifying the cell membrane. This work provides a promising intracellular redox regulatory approach to construct more efficient cell factories.
Peptide Synthesis Utilizing Micro‐flow Technology
Authors: Fuse Shinichiro , Otake Yuma , Nakamura Hiroyuki
Published: October 2018

Peptide drugs have garnered much attention in recent years. However, conventional peptide synthesis requires an excess amount of expensive reagents of low atom economy, and the large amount of waste produced by these reagents complicates the purification of desired peptides. Solid‐phase approaches simplify the purification of these peptides, but these require expensive solid‐phase, excess amounts of reagents, substrates, and solvents. This makes it important to develop high‐yielding, cost‐effective, and less wasteful synthetic approaches. Micro‐flow technology (reaction space ≤1 mm) has produced many advantages over conventional batch synthesis. The advantages include precise control of short reaction time and temperature, high levels of light penetration efficiency, lowered risks of handling dangerous compounds, and ready scale‐up with high reproducibility. Micro‐flow peptide syntheses using these advantages have been reported in recent years. This review summarizes the solid‐phase and solution‐phase syntheses of α‐ and β‐peptides and of cyclic peptides using micro‐flow technology.
Impacts of the −1 Amino Acid on Yeast Production of Protein‐Intein Fusions
Authors: Goulatis Loukas I. , Ramanathan Rasika , Shusta Eric V.
Published: October 2018

Expressing antibodies as fusions to the non‐self‐cleaving Mxe GyrA intein allows for site‐specific chemical functionalization via expressed protein ligation. It is highly desirable to maximize the yield of functionalizable protein; and previously an evolved intein, 202‐08, was identified that could increase protein fusion production in yeast. Given that the −1 amino acid residue upstream of inteins can affect cleavage efficiency, we examined the effects of amino acid variability at this position on 202‐08 intein cleavage efficiency and secretion yield. Varying the −1 residue resulted in a wide range of cleavage behaviors with some amino acids yielding substantial autocleaved product that could not be functionalized. Autocleavage was noticeably higher with the 202‐08 intein compared with the wild‐type Mxe GyrA intein and resulted directly from the catalytic activity of the intein. Refeeding of production cultures with nitrogen base and casamino acids reduced, but did not eliminate autocleavage, while increasing protein‐intein production up to seven‐fold. Importantly, two amino acids, Gly and Ala, at the −1 position resulted in good cleavage efficiency with no undesirable autocleavage, and can be used in concert with refeeding strategies to increase total functionalizable protein yield for multiple protein fusion partners. Taken together, we describe an optimized yeast expression platform for protein‐intein fusions. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2736, 2019
Coumarin Triazabutadienes for Fluorescent Labeling of Proteins
Authors: Shadmehr Mehrdad , Davis Garrett J. , Mehari Bereketab T. , Jensen Stephanie M. , Jewett John C.
Published: October 2018

The use of small‐molecule fluorophores to label proteins with minimal perturbation in response to an external stimulus is a powerful tool to probe chemical and biochemical environments. Herein, we describe the use of a coumarin‐modified triazabutadiene that can deliver aryl diazonium ions to fluorescently label proteins by tyrosine‐selective modification. The labeling can be triggered by low‐pH‐induced liberation of the diazonium species, thus making the fluorophore especially useful in labeling biochemical surroundings such as those found within the late endosome. Additionally, we show that a variety of coumarin triazabutadienes might also be prone to releasing their diazonium cargo after irradiation with UV light.
Clinical outcomes in unselected patients treated with the PROMUS Element platinum‐chromium, everolimus‐eluting stent: Final five‐year results from the PE PROVE Study
Authors: Moreno Raul , Legrand Victor , Ferrario Maurizio , MacCarthy Philip , Redwood Simon , Werner Nikos , Jung Werner , Ungi Imre , Zaman Azfar , Richardt Gert , Crowley James , Schwimmbeck Peter , Christen Thomas , Allocco Dominic J. , Meredith Ian T.
Published: October 2018

Objectives

The goal of this analysis was to evaluate the final 5‐year safety and effectiveness of the PROMUS Element platinum‐chromium everolimus‐eluting stent in unselected patients treated in routine clinical practice.

Background

The prospective, open‐label PROMUS Element™ European Post‐Approval Surveillance Study (PE‐PROVE) enrolled 1,010 “real‐world” patients who received the PROMUS Element stent. Adverse event rates were low at 1‐year, and the incidence of stent thrombosis was 0.6%.

Methods

The primary endpoint was target vessel failure (TVF; overall and PE stent‐related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1‐year post‐implantation. Five‐year clinical outcomes were evaluated in overall as well as high‐risk patient subgroups.

Results

The overall 5‐year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5‐year follow‐up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high‐risk subgroups.

Conclusions

The final 5‐year data from the PE‐PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in “real‐world” patients with coronary artery disease.
Counterpulsation requires pulsation: IABP use in patients with heart failure without acute MI
Authors: Kapur Navin K. , Hirst Colin S.
Published: October 2018

Key Points

Limited data exploring the utility of IABPs in shock without acute myocardial infarction exist.

Counterpulsation pumps depend on native LV contractile function.

Hemodynamic monitoring with a pulmonary artery catheter should help guide management of the cardiogenic shock patient.

More studies are required to identify the optimal patient population and hemodynamic parameters best suited for IABP therapy.
Waiting for Godot: Anticipating answers on embolic protection unlikely to arrive
Authors: Anouti Khalil , Gray William A.
Published: October 2018

Key Points

For symptomatic and asymptomatic patient with high or intermediate risk of CEA complications, CAS with the use of EPDs has a very low rate of in‐hospital stroke and death

There is no statistically significant difference in ipsilateral stroke/TIA and any stroke/TIA between the different device platforms

Further efforts to assess differences between EPD devices would likely need to involve a surrogate endpoint due to the very low rates of clinical events
Bioresorbable vascular scaffold for the treatment of coronary in‐stent restenosis: New dawn or frost on snow?
Authors: Ge Junbo
Published: October 2018

Key Points

BVS might be non‐inferiority compared to DES or DEB in ISR treatment in terms of 1‐year DOCE.

BVS, especially thinner‐strut stent may be an attractive alternative in ISR setting.

Large prospective randomized trials are needed to provide convince evidences to direct clinical practice in the future.
Caution: Predictors ahead
Authors: Balter Stephen , Moses Jeffrey W.
Published: October 2018

Key Points

Radiation dose data can be used as a starting point to establish local TAVR reference levels.

Cancer risk is of concern but is very low in the context of TAVR patients.

Improvements in clinical radiation management will reduce both patient and staff risk for all procedures.
TAVR and SAVR in ESRD: Just because we can doesn't necessarily mean that we should
Authors: Hensey Mark , Webb John G.
Published: October 2018

Key Points

In patients with end stage renal disease on hemodialysis, TAVR resulted in reduced length of stay, hospitalization cost, complication rate and higher rates of home discharge compared to SAVR.

In‐hospital mortality and complication rates were high in both groups.

Careful patient selection and further research is required to identify patients with end‐stage renal disease who might, or might not, benefit from intervention.
Are all P2Y12 equally effective in vein graft angioplasty? A report from the UK database
Authors: Berladi Jorge , Lamelas Pablo M.
Published: October 2018

Key Points

Information of P2Y12 inhibitors in acute coronary syndromes with vein graft angioplasty is limited.

This new analysis from the UK database was not able to find significant differences between Clopidogrel, Prasugrel and Ticagrelor.

Large trials would be needed to reliably confirm the best antiplatelet regimen in this setting.
Relative importance of attribute preferences for radial vs. femoral arterial access: A crowdsourcing study of healthy online‐recruited volunteers
Authors: Ross Jason , Vidovich Mladen I.
Published: October 2018

Introduction: Percutaneous coronary intervention (PCI) is typically performed with vascular access provided by the radial or femoral artery. However, little is known about how patients value aspects of these different vascular access approaches.

Methods: Conjoint analysis is a survey‐based statistical technique used in market research that helps determine how individuals value different attributes that make up a particular product or services. We utilized conjoint analysis to assess the relative importance of four attributes associated with PCI: access site, risk of bleeding, hospital stay, and radiation exposure. Participants were healthy individuals recruited by Amazon Mechanical Turk (MTURK). After completing a conjoint analysis survey, the software Conjoint.ly was used to calculate the relative importance for these four different attributes of PCI.

Results: The relative importance of hospital stay, radiation exposure, bleeding risk, and procedure site was 32.7% (95% CI 29.5–35.8), 27.3% (95% CI 24.8–29.8), 24.4% (95% CI 22.3–26.5), and 15.7% (95% CI 13.6–17.8), respectively. The difference between these groups was statistically significant (P‐value < 0.00001). The difference between duration of hospital stay and radiation exposure was statistically significant (P‐value < 0.00433).

Conclusion: Patients undergoing PCI place largest relative value on duration of hospital stay. Access site appears the least valued attribute. These findings carry implications to guide further research on access site choices and the consent process in the context of shared decision‐making.
A Hexanuclear Niobium Cluster Compound With Intra‐Cluster Chelate Ligands: [Nb6(OC2H4NH2)12]I3
Authors: Weiß Daniel Holger , Köckerling Martin
Published: October 2018

From the reaction of [Nb6I11] with 2‐aminoethanol in pyridine the cluster compound [Nb6(OC2H4NH2)12]I3 has been obtained and the single‐crystal X‐ray structure determined. It represents the first example of a group VB metal cluster compound with hexanuclear, octahedral metal atom core, which carries intra‐cluster chelate ligands. With the formation of this unprecedented cluster cation we report for the first time a transformation of a 6–8 to a 6–12 type cluster unit. The formation of the cluster cation goes along with a one‐electron oxidation of the cluster starting material. Furthermore, it adds a second entry to the so far very small group of M6 cluster compounds with organic ligands on the inner cluster sites.
Hydrogen Atom Transfer‐Mediated Cyclisations of Nitriles
Authors: Turner Oliver J. , Murphy John A. , Hirst David J. , Talbot Eric P. A.
Published: October 2018

Hydrogen atom transfer‐mediated intramolecular C−C coupling reactions between alkenes and nitriles, using PhSiH3 and catalytic Fe(acac)3, are described. This introduces a new strategic bond disconnection for ring‐closing reactions, forming ketones via imine intermediates. Of note is the scope of the reaction, including formation of sterically hindered ketones, spirocycles and fused cyclic systems.
Monitoring the behaviour of anionic polymer‐anionic surfactant stabilized foam in the absence and presence of oil: Bulk and bubble‐scale experimental analyses
Authors: Veyskarami Maziar , Hossein Ghazanfari Mohammad , Shafiei Yousef
Published: October 2018

The present study aims at monitoring the bulk and bubble‐scale behaviour of anionic polyacrylamide‐sodium dodecyl sulphate stabilized foam in the absence and presence of oil. Dynamic stability tests provided results indicating that polymer increases the foam dynamic stability and decreases the drainage. Oil slows down the drainage rate of polymer‐surfactant foam. In the absence of oil, foam is drained gradually/smoothly whereas remarkable fluctuations are evident in drainage graphs when oil is present. The Hele‐Shaw cell was employed to conduct bubble‐scale as well as statistical analyses on how foam texture is influenced by a polymer‐surfactant system and hydrocarbon. Bubble‐scale analyses, taken right after foam generation in the absence of oil, revealed that foam bubble sizes and their standard deviation increase by polymer concentration. The coefficient of variation of foam bubble sizes drops with polymer concentration in the absence/presence of oil, meaning the growth of foam texture uniformity. Oil increases the bubble size diversity in the foam texture. Disproportionation/Ostwald ripening is hindered by increasing the foam bubble distribution uniformity by adding polymer to the foaming solution. At polymer concentrations higher than 13 × 10−4 g/g, a polymer‐surfactant mixture generates foam in the presence of oil as stable as foam in the absence of oil, while at the polymer concentrations lower than 7 × 10−4 g/g, bubbles are highly unstable when oil is present. Results of this study help to gain a better understanding about the extent to which polymer could enhance the foam stability in bulk/bubble‐scale, which might be applicable for enhanced oil recovery operations.
Cognitive–behavioral therapy for Internet gaming disorder: A systematic review and meta‐analysis
Authors: Stevens Matthew W.R. , King Daniel L. , Dorstyn Diana , Delfabbro Paul H.
Published: October 2018

Objective

Although there is sufficient research and clinical evidence to support the inclusion of gaming disorder in the latest revision of the International Classification of Diseases, relatively little is known about the effectiveness of first‐line psychological treatment for gaming disorder or internet gaming disorder (IGD) as it is listed in the Diagnostic and Statistical Manual. This systematic review employed meta‐analytic techniques to determine the effectiveness of cognitive–behavioural therapy (CBT) for IGD on four key outcomes: IGD symptoms, anxiety, depression, and time spent gaming.

Method

A database search identified 12 independent CBT studies. Effect size estimates (Hedges' g) with associated confidence intervals, prediction intervals, and p values for each pre–post treatment outcome, were calculated. Study reporting quality was evaluated in accordance with the Consolidated Standards of Reporting Trials guidelines. Subgroup and moderator analyses were undertaken to investigate potential sources of heterogeneity.

Results

CBT demonstrated high efficacy in reducing IGD symptoms (g = 0.92; [0.50, 1.34]) and depression (g = 0.80, [0.21, 1.38]), and showed moderate efficacy in reducing anxiety (g = 0.55, [0.17, 0.93]) at post‐test. There was insufficient power to determine whether CBT was capable of reducing time spent gaming. Treatment gains at follow‐up were nonsignificant across the four treatment outcomes.

Conclusions

The pooled findings suggest that CBT for IGD is an effective short‐term intervention for reducing IGD and depressive symptoms. However, the effectiveness of CBT for reducing actual time spent gaming was unclear. Given the limitations of this evidence base, there is a need for more rigorous studies to determine the potential long‐term benefits of CBT for IGD.

Public Health Significance Statement

Given the rise in treatment demand for internet gaming disorder (IGD) and problematic gaming, it is necessary to determine which treatments are most effective for whom and under which conditions. This review shows that cognitive‐behavioural therapy for IGD, which is often considered the first‐line therapy, can improve IGD symptoms and comorbid depression. However, treatment gains tend to be short‐term and their effect in reducing time spent gaming is unclear. Programs that target problematic gaming may be improved by additional support beyond the standard program of therapy sessions. More funding and resources are needed to support the development of a more rigorous evidence base on IGD and its treatment.
Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges
Authors: Sardela Vinicius Figueiredo , Anselmo Carina de Souza , Nunes Isabelle Karine da Costa , Carneiro Gabriel Reis Alves , dos Santos Gustavo Ramalho Cardoso , de Carvalho Aline Reis , Labanca Bruna de Jesus , Silva Oliveira Daniely , Ribeiro William Dias , de Araujo Amanda Lessa Dutra , Padilha Monica Costa , de Lima Cleverton Kleiton Freitas , de Sousa Valeria Pereira , de Aquino Neto Francisco Radler , Gualberto Pereira Henrique Marcelo
Published: October 2018

Zebrafish (Danio rerio) water tank (ZWT) approach was investigated as an alternative model for metabolism studies based on six different experiments with four model compounds. Sibutramine was applied for the multivariate optimization of ZWT conditions, also for the comparison of the metabolism among ZWT, humans and mice, beyond for the role of CYP2B6 in ZWT. After the optimization, 18 fish and 168 hours of experiments is the minimum requirement for a relevant panel of biotransformation products. A comparison among the species resulted in the observation of the same hydroxylated metabolites, with differences in metabolites concentration ratio. However, the ZWT allowed tuning of the conditions to obtain a specific metabolic profile, depending on the need. In addition, by utilizing CYP2B6 inhibition, a relevant ZWT pathway for the demethylation of drugs was determined. The stereospecificity of the ZWT metabolism was investigated using selegiline and no racemization or inversion transformations were observed. Moreover, the investigation of metabolism of cannabimimetics was performed using JWH‐073 and the metabolites observed are the same described for humans, except for the hydroxylation at the indol group, which was explained by the absence of CYP2C9 orthologs in zebrafish. Finally, hexarelin was used as a model to evaluate studies by ZWT for drugs with low stability. As a result, hexarelin displays a very fast metabolization in ZWT conditions and all the metabolites described for human were observed in ZWT. Therefore, the appropriate conditions, merits, and relevant limitations to conduct ZWT experiments for the investigation of drug metabolism are described.
Gold‐Decorated Nanodiamonds: Powerful Multifunctional Materials for Sensing, Imaging, Diagnostics, and Therapy
Authors: Orlanducci Silvia
Published: October 2018

Gold‐decorated nanodiamonds is an interesting multifunctional material that can find space in numerous applications in the biological field. The coupling and/or synergy of the properties of the individual components can offer interesting solutions in the field of optical labeling, imaging, molecule and drug delivery, and biosensing. This microreview describes the techniques used for the synthesis of these materials and includes a critical discussion of some recent results on their application. The synergy between the two particles is particularly evident in the improvement of the plasmonic and photoacoustic properties of gold. In addition, the catalytic and sensor activity of the hybrid system shows peculiarities not found in the individual components alone.
The impact of parameter uncertainty in insurance pricing and reserve with the temperature‐related mortality model
Authors: Seklecka Malgorzata , Pantelous Athanasios A. , O'Hare Colin
Published: October 2018

Changes in mortality rates have an impact on the life insurance industry, the financial sector (as a significant proportion of the financial markets is driven by pension funds), governmental agencies, and decision makers and policymakers. Thus the pricing of financial, pension and insurance products that are contingent upon survival or death and which is related to the accuracy of central mortality rates is of key importance. Recently, a temperature‐related mortality (TRM) model was proposed by Seklecka et al. (Journal of Forecasting, 2017,36(7), 824–841), and it has shown evidence of outperformance compared with the Lee and Carter (Journal of the American Statistical Association, 1992,87, 659–671) model and several others of its extensions, when mortality‐experience data from the UK are used. There is a need for awareness, when fitting the TRM model, of model risk when assessing longevity‐related liabilities, especially when pricing long‐term annuities and pensions. In this paper, the impact of uncertainty on the various parameters involved in the model is examined. We demonstrate a number of ways to quantify model risk in the estimation of the temperature‐related parameters, the choice of the forecasting methodology, the structures of actuarial products chosen (e.g., annuity, endowment and life insurance), and the actuarial reserve. Finally, several tables and figures illustrate the main findings of this paper.
Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Authors: Yan Jinhua , Yao Bin , Kuang Hongyu , Yang Xubin , Huang Qin , Hong Tianpei , Li Yushu , Dou Jingtao , Yang Wenying , Qin Guijun , Yuan Huijuan , Xiao Xinhua , Luo Sihui , Shan Zhongyan , Deng Hongrong , Tan Ying , Xu Fen , Xu Wen , Zeng Longyi , Kang Zhuang , Weng Jianping
Published: October 2018

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add‐on liraglutide, sitagliptin, or insulin glargine in this 26‐week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging–estimated proton density fat fraction (MRI‐PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent‐to‐treat population. MRI‐PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI‐PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI‐PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.
Theoretical study of proton coupled electron transfer reaction in the light state of the AppA BLUF photoreceptor
Authors: Xu Yang , Bao Peng , Song Kai , Shi Qiang
Published: October 2018

The BLUF (blue light sensor using flavin adenine dinucleotide) domain is widely studied as a prototype for proton coupled electron transfer (PCET) reactions in biological systems. In this work, the photo‐induced concerted PCET reaction from the light state of the AppA BLUF domain is investigated. To model the simultaneous transfer of two protons in the reaction, two‐dimensional potential energy surfaces for the double proton transfer are first calculated for the locally excited and charge transfer states, which are then used to obtain the vibrational wave function overlaps and the vibrational energy levels. Contributions to the PCET rate constant from each pair of vibronic states are then analyzed using the theory based on the Fermi's golden rule. We show that, the recently proposed light state structure of the BLUF domain with a tautomerized Gln63 residue is consistent with the concerted transfer of one electron and two protons. It is also found that, thermal fluctuations of the protein structure, especially the proton donor‐acceptor distances, play an important role in determining the PCET reaction rate. © 2018 Wiley Periodicals, Inc.
A Theoretical study on the charge and discharge states of Na‐ion battery cathode material, Na1+xFePO4F
Authors: Shinagawa Chikashi , Morikawa Yusuke , Nishimura Shin‐ichi , Ushiyama Hiroshi , Yamada Atsuo , Yamashita Koichi
Published: October 2018

Na2FePO4F is a promising cathode material for a Na‐ion battery because of its high electronic capacity and good cycle performance. In this work, first principle calculations combined with cluster expansion and the Monte Carlo method have been applied to analyze the charge and discharge processes of Na2FePO4F by examining the voltage curve and the phase diagram. As a result of the density functional theory calculation and experimental verification with structural analysis, we found that the most stable structure of Na1.5FePO4F has the P21/b11 space group, which has not been reported to date. The estimated voltage curve has two clear plateaus caused by the two‐phase structure composed of P21/b11 Na1.5FePO4F and Pbcn Na2FePO4F or Na1FePO4F and separated along the c‐axis direction. The phase diagram shows the stability of the phase‐separated structure. Considering that Na2FePO4F has diffusion paths in the a‐ and c‐axis directions, Na2FePO4F has both innerphase and interphase diffusion paths. We suggest that the stable two‐phase structure and the diffusion paths to both the innerphase and interphases are a key for the very clear plateau. We challenge to simulate a nonequilibrium state at high rate discharge with high temperature by introducing a coordinate‐dependent chemical potential. The simulation shows agreement with the experimental discharge curve on the disappearance of the two plateaus. © 2018 Wiley Periodicals, Inc.
Prenatal exposure to valproate induces sex‐, age‐, and tissue‐dependent alterations of cholesterol metabolism: Potential implications on autism
Authors: Cartocci Veronica , Tonini Claudia , Di Pippo Tiziana , Vuono Florenzia , Schiavi Sara , Marino Maria , Trezza Viviana , Pallottini Valentina
Published: October 2018

Here, we investigated the protein network regulating cholesterol metabolism in the liver and brain of adolescent and adult male and female rats prenatally exposed to valproate (VPA), a well validated experimental model of autism spectrum disorders (ASD). We were aimed at studying whether prenatal VPA exposure affected the proteins involved in cholesterol homeostasis in a sex‐dependent manner. To this aim the protein network of cholesterol metabolism, in term of synthesis and plasma membrane trafficking, was analyzed by western blot in the liver and different brain areas (amygdala, cerebellum, cortex, hippocampus, nucleus accumbens, and dorsal striatum) of adolescent and adult male and female rats prenatally exposed to VPA. Our results show that physiological sex‐dependent differences are present both in the liver and in brain of rats. Interestingly, VPA affects specifically the brain in an age‐ and region‐specific manner; indeed, cerebellum, cortex, hippocampus and nucleus accumbens are affected in a sex‐dependent way, while this does not occur in amygdala and dorsal striatum. Overall, we demonstrate that each brain area responds differently to the same external stimulus and males and females respond in a different way, suggesting that this could be related to the diverse incidences, between the sexes, of some neurodevelopmental pathologies such as autism, which displays a 3:1 male to female ratio.
Heat stress induces distinct responses in porcine cumulus cells and oocytes associated with disrupted gap junction and trans‐zonal projection colocalization
Authors: Yin Chao , Liu Jie , He Bin , Jia Longfei , Gong Yabin , Guo Huiduo , Zhao Ruqian
Published: October 2018

Cumulus cells (CCs), the granulosa cells surrounding the oocytes, play critical roles in oocytes maturation through intercellular communication by extending trans‐zonal projections (TZPs) to contact oocytes via gap junctions (GJs). The adverse effect of heat stress (HS) on oocyte maturation has been well documented, whereas the HS responses of CCs and the oocytes in association with GJ/TZP colocalization remain unclear. In this study, porcine cumulus‐oocyte complexes (COCs) were subjected to HS at 41.5°C for 24 hr during in vitro maturation. Cumulus expansion was impaired and oocyte quality was reduced with lower survival rate, polar body extrusion rate, and early embryo developmental potentials. CCs and oocytes isolated from COCs demonstrated distinct responses to HS. The messenger RNA abundance of heat shock protein‐related genes and mitochondrial DNA‐encoded genes, together with ATP content, were significantly increased in CCs, yet decreased in oocytes, despite activation of caspase 3 detected in both CCs and oocytes. Similar changes were observed when denuded oocytes and isolated CCs subjected to HS separately, except mitochondria reactive oxygen species (mROS). In heat‐stressed COCs, mROS was significantly increased only in oocytes. However, when isolated CCs and denuded oocytes were heat‐stressed separately, mROS was significantly increased only in CCs. Moreover, F‐actin, a TZP marker, and its colocalization with a GJ protein connexin‐45, were significantly reduced in heat‐exposed COCs. These results indicate that HS induces distinct responses in porcine CCs and oocytes in association with disrupted GJ and TZP colocalization.
MiR‐128‐3p accelerates cardiovascular calcification and insulin resistance through ISL1‐dependent Wnt pathway in type 2 diabetes mellitus rats
Authors: Wang Xin‐Yong , Zhang Xian‐Zhao , Li Feng , Ji Qing‐Rong
Published: October 2018

Vascular calcification is highly prevalent in patients with type 2 diabetes mellitus (T2DM), one of the most common chronic diseases with high morbidity and mortality. In recent years, microRNAs have been widely reported as potential biomarkers for the diagnosis and treatment of T2DM. We hypothesized that miR‐128‐3p is associated with cardiovascular calcification and insulin resistance (IR) in rats with T2DM by targeting ISL1 via the Wnt pathway. Microarray analysis was adopted to identify differentially expressed genes related to T2DM. T2DM models were induced in rats. Blood samples from normal and T2DM rats were used to detect islet β‐cell function, islet sensitivity, and calcium content. Next, islet tissues were obtained to identify the expression of miR‐128‐3p, ISL1, and the Wnt signaling pathway‐ and apoptosis‐related genes. Finally, apoptosis of islet β‐cells was determined by flow cytometry. Through microarray analysis of GSE27382 and GSE23343, ISL1 was found to be downregulated in T2DM. In blood samples from T2DM rats, basic biochemical indicators, IR, and calcium content were increased, and islet sensitivity and islet β‐cell function were decreased. Furthermore, upregulation of miR‐128‐3p and ISL1 gene silencing promoted the expression of Wnt‐1, β‐catenin, GSK‐3β, and Bax and the phosphorylation of β‐catenin and GSK‐3β, inhibited c‐fos, PDX‐1, and Bcl‐2 expression, and enhanced cell apoptosis. The key findings of our study demonstrate that miR‐128‐3p aggravates cardiovascular calcification and IR in T2DM rats by downregulating ISL1 through the activation of the Wnt pathway. Thus, miR‐128‐3p may serve as a potential target for the treatment of T2DM.
Long noncoding RNA OPA‐interacting protein 5 antisense transcript 1 upregulated SMAD3 expression to contribute to metastasis of cervical cancer by sponging miR‐143‐3p
Authors: Chen Xing , Xiong Dongsheng , Yang Huichun , Ye Liya , Mei Shuangshuang , Wu Jinhong , Chen Shanshan , Shang Xianwen , Wang Kai , Huang Lingfei
Published: October 2018

Objectives

SMAD3 is pivotal in the biology functions of various tumors. This study is aiming to study the relationship among SMAD3, long noncoding RNAs (lncRNAs) OPA‐interacting protein 5 antisense transcript 1 (OIP5‐AS1), and miR‐143‐3p, and their effects on cervical cancer.

Methods

In our research, real‐time polymerase chain reaction and western blot assay were conducted to detect the expression level of messenger RNA and protein in tumor tissues and cells. Transfection of lncRNA OIP5‐AS1, miR‐143‐3p, or SMAD3 was performed to investigate their potential effects on the function of cell as well as the relationship among them in cervical cell lines via 3‐(4,5‐dimethylthiazolyl‐2)‐2,5‐diphenyltetrazolium bromide) together with transwell assays or dual‐luciferase reporter assay respectively.

Results

SMAD3, lncRNA OIP5‐AS1 expression is significantly enhanced in cervical cancer tissues and cell lines, but miR‐143‐3p was inhibited. LncRNA OIP5‐AS1 is demonstrated to mediate the physiological process of cervical cancer cells. Moreover, silencing SMAD3 via siRNA suppressed cell number, viability, migration and invasion, whereas overexpression of OIP5‐AS1 promoted these abilities. Furthermore, lncRNA OIP5‐AS1 exert its function via sponging miR‐143‐3p to regulate SMAD3 expression.

Conclusions

LncRNA OIP5‐AS1 promoted SMAD3 expression via mediating miR‐143‐3p to promote migration and invasion of cervical cancer cells.
Circular RNA in cardiovascular disease
Authors: Altesha M‐Ashraf , Ni Tiffany , Khan Afaan , Liu Kexiang , Zheng Xiufen
Published: October 2018

Circular RNA (circRNA) are endogenous transcripts that display differential expression across species, developmental stages, and pathologies. Their lack of free ends confers increased stability when compared with linear transcripts, making them ideal candidates for future diagnostic biomarkers and therapeutic interventions. Increasing evidence has implicated circRNA in the pathogenesis of multiple cardiovascular diseases. In this paper, we summarize current understanding of circRNA biogenesis, properties, expression profiles, detection methods, functions, and their implication in cardiac pathologies including/ischemia reperfusion injury, myocardial infarction, cardiac senescence, cardiac fibrosis, cardiomyopathy, cardiac hypertrophy and heart failure, atherosclerosis, coronary artery disease, and aneurysm.
Helvolic acid attenuates osteoclast formation and function via suppressing RANKL‐induced NFATc1 activation
Authors: Chen Kai , Yuan Yu , Wang Ziyi , Song Dezhi , Zhao Jinmin , Cao Zhen , Chen Junhao , Guo Qiang , Chen Li , Tickner Jennifer , Xu Jiake
Published: October 2018

Excessive osteoclast formation and function are considered as the main causes of bone lytic disorders such as osteoporosis and osteolysis. Therefore, the osteoclast is a potential therapeutic target for the treatment of osteoporosis or other osteoclast‐related diseases. Helvolic acid (HA), a mycotoxin originally isolated from Aspergillus fumigatus , has been discovered as an effective broad‐spectrum antibacterial agent and has a wide range of pharmacological properties. Herein, for the first time, HA was demonstrated to be capable of significantly inhibiting receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis and bone resorption in vitro by suppressing nuclear factor of activated T cells 1 (NFATc1) activation. This inhibition was followed by the dramatically decreased expression of NFATc1‐targeted genes including
Ctr (encoding calcitonin receptor),
Acp5 (encoding tartrate‐resistant acid phosphatase [TRAcP]),
Ctsk (encoding cathepsin K),
Atp6v0d2 (encoding the vacuolar H+ ATPase V0 subunit d2 [V‐ATPase‐d2]) and
Mmp9 (encoding matrix metallopeptidase 9) which are osteoclastic‐specific genes required for osteoclast formation and function. Mechanistically, HA was shown to greatly attenuate multiple upstream pathways including extracellular signal‐regulated kinase (ERK) phosphorylation, c‐Fos signaling, and intracellular Ca
2+ oscillation, but had little effect on nuclear factor‐κB (NF‐κB) activation. In addition, HA also diminished the RANKL‐induced generation of intracellular reactive oxygen species. Taken together, our study indicated HA effectively suppressed RANKL‐induced osteoclast formation and function. Thus, we propose that HA can be potentially used in the development of a novel drug for osteoclast‐related bone diseases.
Colorectal cancer invasiveness in vitro: Predominant contribution of neonatal Nav1.5 under normoxia and hypoxia
Authors: Guzel R. Mine , Ogmen Kazim , Ilieva Kristina M. , Fraser Scott P. , Djamgoz Mustafa B. A.
Published: October 2018

Functional expression of voltage‐gated Na+ channels (VGSCs) occurs in human carcinomas and promotes invasiveness in vitro and metastasis in vivo. Both neonatal and adult forms of Nav1.5 (nNav1.5 and aNav1.5, respectively) have been reported to be expressed at messenger RNA (mRNA) level in colorectal cancer (CRCa) cells. Here, three CRCa cell lines (HT29, HCT116 and SW620) were studied and found to express nNav1.5 mRNA and protein. In SW620 cells, adopted as a model, effects of gene silencing (by several small interfering RNAs [siRNAs]) selectively targeting nNav1.5 or aNav1.5 were determined on (a) channel activity and (b) invasiveness in vitro. Silencing nNav1.5 made the currents more “adult‐like” and suppressed invasion by up to 73%. Importantly, subsequent application of the highly specific, general VGSC blocker, tetrodotoxin (TTX), had no further effect. Conversely, silencing aNav1.5 made the currents more “neonatal‐like” but suppressed invasion by only 17% and TTX still induced a significant effect. Hypoxia increased invasiveness and this was also blocked completely by siRNA targeting nNav1.5. The effect of hypoxia was suppressed dose dependently by ranolazine, but its effect was lost in cells pretreated with nNav1.5‐siRNA. We conclude that (a) functional nNav1.5 expression is common to human CRCa cells, (b) hypoxia increases the invasiveness of SW620 cells, (c) the VGSC‐dependent invasiveness is driven predominantly by nNav1.5 under both normoxic and hypoxic conditions and (d) the hypoxia‐induced increase in invasiveness is likely to be mediated by the persistent current component of nNav1.5.
Upregulation of long noncoding RNA XIST is associated with poor prognosis in human cancers
Authors: Liu Ji‐Long , Zhang Wen‐Qian , Zhao Miao , Huang Ming‐Yu
Published: October 2018

Growing evidence from recent studies has shown that the X‐inactive specific transcript (XIST), a well‐known long noncoding RNA involved in early embryonic development, is aberrantly regulated in various human cancers. However, the prognostic value of XIST in cancers remains uncharacterized. In this study, we searched PubMed, Web of Science, and Embase to collect all relevant studies, and a meta‐analysis was performed to explore the association of XIST expression with overall survival (OS) and clinicopathological parameters. We demonstrated that high XIST expression was associated with poor OS (hazard ratio = 1.76; 95% confidence intervals [CI], 1.56–1.98; p < 0.001). In addition, increased XIST expression was found to be associated with lymph node metastasis (odds ratio [OR] = 2.06; 95% CI, 1.46–1.90;
p < 0.001), distant metastasis (OR = 2.93; 95% CI, 2.00–4.28;
p < 0.001), tumor size (OR = 2.66; 95% CI, 1.86–3.81;
p < 0.001), poor differentiation (OR = 1.45; 95% CI, 1.00–2.10;
p = 0.049), and advanced tumor stage (OR = 3.35; 95% CI, 2.25–5.00;
p < 0.001), but not with age (OR = 0.82; 95% CI, 0.59–1.15;
p = 0.251) or gender (OR = 0.92; 95% CI, 0.70–1.19;
p = 0.512). Our meta‐analysis showed that XIST may be a useful common biomarker for predicting prognosis in patients with cancer.