bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilization of All‐in‐Water Emulsions To Form Capsules as Artificial Cells
Authors: Douliez Jean‐Paul , Perro Adeline , Béven Laure 
Published: May 2019

AbstractBuilding artificial cells through a bottom‐up approach is a remarkable challenge that would be of interest for our understanding of the origin of life, research into the minimal conditions required for life, the formation of bioreactors, and for industrial applications. To date, capsules such as liposomes, including polymersomes, are widely used, but the low membrane permeability and method to encapsulate biological materials within these structures hamper their use. By contrast, all‐in‐water emulsion droplets, including coacervate droplets, are promising compartments, mainly because they can spontaneously sequester chemicals. However, they lack a membrane necessary to control exchange between the inner and outer media. Moreover, droplets tend to coalesce with time, yielding macroscopic phase separation that is deleterious for any use as artificial cells. Recent advances, which are reviewed herein, have shown that such droplets can be stabilized by using lipid membranes, liposomes, polymers, proteins, and particles, and thus, preventing coalescence. Finally, different strategies that could allow the future development of artificial cells from these stabilized all‐in‐water emulsion droplets are discussed.
Molecular Glue for RNA: Regulating RNA Structure and Function through Synthetic RNA Binding Molecules
Authors: Dohno Chikara , Nakatani Kazuhiko 
Published: May 2019

AbstractWe introduce the concept of molecular glues for RNA, in which specific RNA‐binding small molecules induce designed structural changes in target functional RNAs, resulting in modulation of the functions. (Z)‐NCTS is an RNA‐mismatch‐binding small molecule that recognizes 5′‐r(XGG)‐3′/5′‐r(XGG)‐3′ sequences (X=U or A) and acts as a molecular glue for RNA. The binding of (Z)‐NCTS brings two distinct 5′‐r(XGG)‐3′ domains into contact with each other, and this can result in higher‐order structural changes of target RNAs. We applied (Z)‐NCTS to induce the formation of a proposed tertiary structure of a ribozyme together with activation of RNA‐cleaving ability. The concept of a molecular glue could inspire new small‐molecule‐based strategies for regulating biological functions: a synthetic small molecule targeting functional RNAs could regulate the RNA structure and function.
Some Recent Advances in the Design and Use of Molecular Balances for the Experimental Quantification of Intramolecular Noncovalent Interactions of π Systems
Authors: Aliev Abil E. , Motherwell William B. 
Published: May 2019

AbstractHerein, various molecular balances used for comparing the strengths of intramolecular noncovalent interactions are reviewed. Our overview indicates that considerable quantitative insight into the strength of noncovalent interactions can be gained through the careful design of molecular balances. Many exciting opportunities certainly exist for the design of further new balances to quantify and dissect the relative strengths of noncovalent interactions as a function of solvation and the importance of the many factors that contribute to overall molecular recognition. However, even simple model molecules can show a multiplicity of intramolecular noncovalent interactions acting in a combined fashion. It is therefore essential to undertake a detailed computational analysis to identify all possible noncovalent interactions present in a selected molecular balance prior to a quantitative experimental assessment of the strength of a particular noncovalent interaction. It is also argued that the words “torsion” and “molecular balance” seem to have become inextricably linked and, in consequence, even top pan and seesaw balances have been mistakenly referred to in these terms.
A Self‐Assembled Cage with Endohedral Acid Groups both Catalyzes Substitution Reactions and Controls Their Molecularity
Authors: Bogie Paul M. , Holloway Lauren R. , Ngai Courtney , Miller Tabitha F. , Grewal Divine K. , Hooley Richard J. 
Published: May 2019

AbstractA self‐assembled Fe4L6 cage complex internally decorated with acid functions is capable of accelerating the thioetherification of activated alcohols, ethers and amines by up to 1000‐fold. No product inhibition is seen, and effective supramolecular catalysis can occur with as little as 5 % cage. The substrates are bound in the host with up to micromolar affinities, whereas the products show binding that is an order of magnitude weaker. Most importantly, the cage host alters the molecularity of the reaction: whereas the reaction catalyzed by simple acids is a unimolecular, SN1‐type substitution process, the rate of the host‐mediated process is dependent on the concentration of nucleophile. The molecularity of the cage‐catalyzed reaction is substrate‐dependent, and can be up to bimolecular. In addition, the catalysis can be prevented by a large excess of nucleophile, where substrate inhibition dominates, and the use of tritylated anilines as substrates causes a negative feedback loop, whereby the liberated product destroys the catalyst and stops the reaction.
Organic Mesopore Generating Agents (OMeGAs) for Hierarchical Zeolites: Combining Functions on Multiple Scales
Authors: Hong Mei , Dong Lei , Yang Shihe 
Published: May 2019

AbstractIn the synthesis of porous zeolites, small organic molecules usually function as organic structure‐directing agents (OSDAs) or zeolite growth modifiers (ZGMs), while mesoporous zeolites are typically synthesized by employing the physical space‐filling strategy with mesoscale templates including carbons, surfactants, and polymers. Recently, we discovered that a class of small organic molecules including the common amino acids could mediate the formation of zeolite mesopores based on a chemical bond‐breaking mechanism. This class of organic mesopore generating agents (OMeGAs) are distinguished by their ability to form organic anions in situ. In this minireview, we briefly introduce the widely recognized role of OSDA and ZGM, and then focus on the interesting function of OMeGA for the intracrystalline void generation. Comparison of OMeGA with the mesoscale templates especially surfactants are made in terms of their mesopore‐forming mechanisms, and the potential implications on a possible dissociative‐associative crystallization pathway are discussed. We end this review with the prospects of future research on the small molecule OMeGA, such as function integration and structure optimization.
Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis
Authors: Carrothers Timothy J. , Chittenden Jason T. , Critchley Ian 
Published: May 2019

AbstractDalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible gram‐positive microorganisms. This analysis represents the update of the population pharmacokinetics (popPK) modeling and target attainment simulations performed with data from the single‐dose safety and efficacy study and an unrelated but substantial revision of the preclinical pharmacokinetic/pharmacodynamic target (fAUC/MIC, free area under concentration‐time curve/minimum inhibitory concentration ratio). A 3‐compartment distribution model with first‐order elimination provided an appropriate fit, with typical dalbavancin clearance of 0.05 L/h and total volume of distribution of ∼15 L. Impact of intrinsic factors was modest, although statistically significant (P < .05) relationships with total clearance were found for the following covariates: creatinine clearance, weight, and albumin — dose adjustment was only indicated for severe renal impairment. Under the new nonclinical target, simulations of the popPK model projected that >99% of subjects would achieve the nonclinical target at MIC values up to and including 2 mg/L.
Potential‐Energy Surface and Dynamics Simulation of THBDBA: An Annulated Tetraphenylethene Derivative Combining Aggregation‐Induced Emission and Switch Behavior
Authors: Ding Wei‐Lu , Peng Xing‐Liang , Cui Gang‐Long , Li Ze‐Sheng , Blancafort Lluís , Li Quan‐Song 
Published: May 2019

AbstractElectronic structure calculations and nonadiabatic dynamics simulations were carried out on the excited state decay mechanism of a typical aggregation‐induced emission (AIE)‐active molecule, 10,10′,11,11′‐tetrahydro‐5,5′‐bidibenzo[a,d][7]annulenylidene (THBDBA), which was experimentally found to be almost non‐emissive in THF solution but highly luminescent as an aggregate. At the MS‐CASPT2//CASSCF level, the decay path from S1 leads to a conical intersection (CI) seam with the ground state (S0) via a cyclization process of two neighboring phenyl groups. Nonadiabatic dynamics simulations of 367 surface hopping trajectories show that all the structures of hopping points resemble those of the S1/S0 CI seam with cyclized geometry. The final structures of trajectories hopping to S0 belong to either Franck‐Condon (FC) like structures (66.8 %) or cyclized conformers (33.2 %), which agrees well with the experimental result of 23 % cyclization product (Y. Cai et al. Chem. Sci., 2011, 2, 2029–2034). Our results also indicate that long‐time irradiation leads to a photostationary state where the open and cyclized forms interconvert photochemically. The preference for photocyclization over double bond isomerization is due to the rigidity of the dihydrofulvene rings. From the point of view of AIE, the calculations suggest that THBDBA follows our restricted access to a CI (RACI) model because the photocyclization requires large displacements of the phenyl rings. These displacements must be blocked in the aggregate phase, inhibiting the decay and leading to luminescence. Our study contributes to understand the AIE and switch behavior of THBDBA and will be useful to support the design of new molecules with these features.
A per‐protocol initiation of sacubitril/valsartan in an advanced heart failure disease management programme in the Middle East Gulf Region
Authors: Atallah Bassam , Sadik Ziad G. , Hisham Mohamed , Kalagieh Oussama , Hamour Iman , Gabra Guirgis , El Banna Mosaad , Soliman Medhat , Cherfan Antoine , Bader Feras 
Published: May 2019

AbstractAimsThe aim of this study is to evaluate the utilization and success in therapy intensification after initiation of sacubitril/valsartan using a specified protocol within an advanced heart failure and transplant programme in the Middle East Gulf Region.Methods and resultsWe studied a single‐centre, retrospective cohort in a 364‐bedded multi‐speciality hospital located in the United Arab Emirates (February 2016 to July 2017). The advanced heart failure and transplant programme formulated an institutional protocol for initiation of sacubitril/valsartan with defined criteria for switching from angiotensin‐converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB). Prescribing this drug is intended for patients with heart failure with reduced ejection fraction with left ventricular ejection fraction ≤40%. We excluded patients (i) with age below 18 years or (ii) initiated on sacubitril/valsartan from an outside hospital with or without follow‐up in our outpatient clinic. We included 102 patients with an average initial dose of 78.9 ± 44.2 mg twice daily. Only 17 patients were on target doses of ACEI or ARB prior to switching to sacubitril/valsartan. Up‐titration was successful in 55 patients during the follow‐up period. In addition, 6.9% patients were hospitalized with heart failure exacerbation. In patients with elevated baseline serum potassium prior to initiating this medication, the serum potassium levels decreased post‐initiation by 0.5 ± 0.3 mmol/L (P = 0.0008).ConclusionsInitiating sacubitril/valsartan through a defined protocol selects for appropriate candidates and guides starting dose and titration. Overall, significant success can be achieved in replacing ACEI or ARB by sacubitril/valsartan in symptomatic heart failure with reduced ejection fraction patients.
Rare variant association testing for multicategory phenotype
Authors: Bocher Ozvan , Marenne Gaëlle , Saint Pierre Aude , Ludwig Thomas E. , Guey Stéphanie , Tournier‐Lasserve Elisabeth , Perdry Hervé , Génin Emmanuelle 
Published: May 2019

AbstractGenetic association studies have provided new insights into the genetic variability of human complex traits with a focus mainly on continuous or binary traits. Methods have been proposed to take into account disease heterogeneity between subgroups of patients when studying common variants but none was specifically designed for rare variants. Because rare variants are expected to have stronger effects and to be more heterogeneously distributed among cases than common ones, subgroup analyses might be particularly attractive in this context. To address this issue, we propose an extension of burden tests by using a multinomial regression model, which enables association tests between rare variants and multicategory phenotypes. We evaluated the type I error and the power of two burden tests, CAST and WSS, by simulating data under different scenarios. In the case of genetic heterogeneity between case subgroups, we showed an advantage of multinomial regression over logistic regression, which considers all the cases against the controls. We replicated these results on real data from Moyamoya disease where the burden tests performed better when cases were stratified according to age‐of‐onset. We implemented the functions for association tests in the R package “Ravages” available on Github.
Memory improvement in African Americans with amnestic mild cognitive impairment
Authors: Rovner Barry W. , Casten Robin J. , Leiby Benjamin 
Published: May 2019

ObjectiveAmnestic mild cognitive impairment (aMCI) has an uncertain course. Valid methods to evaluate memory change will best identify predictors of course. This issue is especially relevant to older persons in minority groups, who may have encountered life course factors that adversely affect cognition.Methods/DesignGrowth curve mixture models were used to identify trajectories of memory test scores obtained every 6 months over 2 years in 221 African Americans with aMCI.ResultsParticipants sorted into two classes, with clinically and statistically significant differences in memory scores over time. Class 1 (n = 28 [14.7%]) had sustained improved scores. Class 2 (n = 162 [85.3%]) scores remained low, fluctuated, or declined. Class 1 had better baseline cognition and daily function than class 2.ConclusionsThe observed rate of improved memory is lower than reported reversion rates from aMCI to normal cognition. Evaluating trajectories of memory test scores rather than changes in categorical diagnoses of aMCI, which may depend on recalling (or not recalling) one or two words, may yield a more valid indicator of cognitive change.These approaches require further study in minority groups.
Intricate role of yes‐associated protein1 in human liver cirrhosis: TGF‐β1 still is a giant player
Authors: Mohagheghi Sina , Geramizadeh Bita , Nikeghbalian Saman , Khodadadi Iraj , Karimi Jamshid , Khajehahmadi Zohreh , Gharekhanloo Farideh , Tavilani Heidar 
Published: May 2019

AbstractNumerous investigations have been performed on the role of the transforming growth factor‐β1 (TGF‐β1) pathway in the development of chronic liver diseases (CLDs); however, they failed to explain the underlying mechanism of its pathogenesis, suggesting that other alternative pathways might have been overlooked. The involvement of yes‐associated protein1 (YAP1) has been attributed to liver fibrosis; yet, the precise function of this protein has not been fully understood. Therefore, this study aimed to investigate the activity of the YAP1 pathway in human liver cirrhosis (regardless of its causality) and its correlation with the TGF‐β1 and sonic hedgehog (SHH) pathways. In this case–control study, the immunohistochemical and quantitative real‐time polymerase chain reaction analyses were carried out to determine the activation of the YAP1 pathway in patients with liver cirrhosis (n = 38) and control 1 individuals (n = 10). The western blot analysis and ELISA method were also performed to assess the SHH and TGF‐β1 pathways. Although significantly increased expression of cytoplasmic YAP1 was found in patients with liver cirrhosis (P < 0.045), the rate of the nuclear YAP1 expression was similar to that of the control 1 subjects. Moreover, the hepatic expression of amphiregulin (AREG), known as the YAP1 target, along with proteins involved in the TGF‐β1 pathway was significantly elevated in all cirrhotic patients, compared with the control subjects. Our results showed that the increased activity of the TGF‐β1 pathway is strongly associated with the expression of AREG, denoting a direct and positive relationship between the TGF‐β1 and YAP1 pathways. It seems that, unlike the TGF‐β1 and SHH pathways, the YAP1 pathway does not play a significant role in the development of liver cirrhosis.
Visible light‐induced photocatalytic and antibacterial activity of N‐doped TiO2
Authors: Iwatsu Misato , Kanetaka Hiroyasu , Mokudai Takayuki , Ogawa Toru , Kawashita Masakazu , Sasaki Keiichi 
Published: May 2019

AbstractPrevious reports of some studies have described that nitrogen (N)‐doped titanium dioxide (TiO2) exhibits photocatalytic antibacterial activity under visible light irradiation and that reactive oxygen species (ROS) is involved in its activity. For prevention and treatment of peri‐implantitis, an inflammatory lesion caused by the bacterial infection of plaque adhering to the circumference of an implant, we considered that applying N‐doped TiO2 to dental implant surfaces can be effective. For this study, we aimed at evaluating visible light‐induced antibacterial activity of titanium (Ti) treated with NaOH and hot water, and subsequently heated in an ammonia (NH3) gas atmosphere at 500°C for 3 hr to quantify the generated amount of ROS available for antibacterial activity. N‐doped anatase‐type titania (TiO2‐xNx) is formed on the Ti substrate surface. Under visible light, markedly more hydroxyl radicals were generated with a nitrogen‐doped titanium dioxide plate than with a pure titanium plate. Hydrogen peroxide exhibited the same tendency. Furthermore, it showed visible light‐induced antibacterial effects over Escherichia coli. Results demonstrate that N‐doped TiO2 can be useful as a dental implant surface with low risk of postoperative infection when using visible light irradiation.
Evaluating the Clinical Impact of Formulation Variability: A Metoprolol Extended‐Release Case Study
Authors: Kim Sarah , Sharma Vishnu D. , Lingineni Karthik , Farhan Nashid , Fang Lanyan , Zhao Liang , Brown Joshua D. , Cristofoletti Rodrigo , Vozmediano Valvanera , Ait‐Oudhia Sihem , Lesko Lawrence J. , Trame Mirjam N. , Schmidt Stephan 
Published: May 2019

AbstractThe objective of this research was to evaluate the impact of changes in the formulation of metoprolol extended‐release (ER) tablets on dissolution, pharmacokinetic, and exercise‐induced heart rate (EIHR) using a combined physiologically based absorption pharmacokinetic, and population pharmacokinetic/pharmacodynamic modeling and simulation approach. Using a previously developed physiologically based absorption pharmacokinetic model in DDDPlus and GastroPlus, we simulated the changes in drug release and exposure as the result of quantitative changes in the release‐controlling excipient, hydroxylpropylmethylcellulose, for 50 and 200 mg. The similarity of dissolution profiles was assessed using thef2test, and bioequivalence was tested on the simulated pharmacokinetic profiles. We used the simulated concentration‐time profiles following formulation changes as pharmacokinetic input into a population pharmacokinetic/pharmacodynamic model newly developed in NONMEM to determine if changes in pharmacokinetics lead to clinically significant changes in pharmacodynamics. Pharmacodynamic assessment was based on the percentage reduction in the EIHR from baseline. Therapeutic effect was considered similar when the model‐predicted EIHR was within 50% to 85% of the average maximum EIHR of healthy 30‐year‐old subjects. A 40% or more increase in the release rate constant resulted in dissimilarity in dissolution profiles and bioINequivalence in pharmacokinetics for both 50 and 200 mg. Formulation‐related differences in drug release of metoprolol ER tablets can lead to differences in pharmacokinetics. However, the evaluated pharmacokinetic differences do not lead to clinically meaningful differences in EIHR, suggesting that EIHR may not be sensitive enough to detect changes in pharmacokinetics of metoprolol ER products.
Optic nerve sonography and ophthalmic artery Doppler velocimetry in healthy pregnant women: an Australian cohort study
Authors: Kane Stefan C. , Dennis Alicia T. , Da Silva Costa Fabrício , Kornman Louise H. , Cade Thomas J. , Brennecke Shaun P. 
Published: May 2019

ABSTRACTPurposeMaternal ocular sonography offers a window into cerebrovascular and intracranial pressure changes in pregnancy. This study aimed to determine the Doppler velocimetric variables of the ophthalmic artery, and the mean diameter of the optic nerve sheath (ONSD), in an Australian cohort of healthy pregnant women.MethodsA prospective observational cohort study of healthy women with uncomplicated singleton pregnancies in the third trimester was undertaken in a tertiary maternity service. A single prenatal ultrasonographic examination was performed on all participants, with a postnatal examination performed on a subgroup with uncomplicated deliveries.ResultsFifty women were examined at a mean gestation of 35 weeks. The mean ± SD Doppler variables in the ophthalmic artery were peak systolic velocity (PSV) 41.89 ± 13.13 cm/s, second peak velocity 20.63 ± 8.97 cm/s, end diastolic velocity 9.29 ± 5.13 cm/s, pulsatility index 1.97 ± 0.53, resistive index 0.78 ± 0.07, peak ratio (second peak velocity/PSV) 0.49 ± 0.12, while the mean ONSD was 4.34 ± 0.4 mm. None of these variables had a demonstrable relationship with gestation or mean arterial pressure (MAP), nor did the sheath diameter have a relationship with any of the Doppler variables.ConclusionsThe ocular sonographic variables observed in this population are similar to those reported in other cohorts. No clear relationship could be identified in this cohort between ophthalmic artery Doppler variables and the ONSD, and between each of these variables and gestation or MAP.
Scanning electron microscopy and histomorphology of the epiglottis in dromedaries: A study revealing unusual structure with the probable functional role
Authors: Eshrah Eman A. , Kassab Ahmed A. 
Published: May 2019

AbstractWhile epiglottis is essentially a mammalian structure, studying its microstructure in any placental model will add an important information to the field of comparative anatomy and the related branches of biology. The aim of this study was to describe the structure of the epiglottis in dromedary camels using light and scanning electron microscopy (SEM), with reference to the possible functions. A total of 11 epiglottis cartilages from 11 larynges were used. The study revealed unusual, deeply situated glands just beneath the cartilage plate. They have unusually, wide surface‐openings, while their ducts were partly located within the cartilage. This is presumed to be an adaptation to the need for rapid and efficient mucosal surface hydration in the arid conditions. The possible secretion transport mechanisms in these glands were also discussed. Furthermore, the SEM revealed for the first time, the presence of taste buds in camel epiglottis. However, in histological sections, visibility of taste buds was dependent upon the staining techniques. The taste buds were not seen with standard H& E stain, as they blended imperceptibly with the surrounding epithelium. Conversely, Mallory's trichrome showed contrasting colors, and taste buds were visible. In conclusion, camel epiglottis has an unusual structure, which may be correlated to environmental adaptation and important for the general health of upper respiratory tract in this species.