bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Dynamic and Conformational Features of Human STING in Response to 2′3′‐cGAMP and c‐di‐GMP
Authors: Guo Jingjing , Wang Jie , Fan Jingrong , Zhang Yan , Dong Wenpei , Chen Chang‐Po 
Published: March 2019

AbstractThe human stimulator of interferon genes protein (hSTING) can bind cyclic dinucleotides (CDNs) to activate the production of type I interferons and inflammatory cytokines. These CDNs can be either bacterial secondary messengers, 3′3′‐CDNs, or endogenous 2′3′‐cGAMP. cGAMP, with a unique 2′–5′ bond, is the most potent activator of hSTING among all CDNs. However, current understanding of the molecular principles underlying the unique ability of 2′3′‐cGAMP to potently activate hSTINGs other than 3′3′‐CDNs remains incomplete. In this work, molecular dynamics simulations were used to provide an atomistic picture of the binding of 2′3′‐cGAMP and one 3′3′‐CDN (c‐di‐GMP) to hSTING. The results suggest that hSTING binds more strongly to 2′3′‐cGAMP than to c‐di‐GMP, which prefers to bind with a more open and flexible state of hSTING. Finally, a potential “dock–lock–anchor” mechanism is proposed for the activation of hSTING upon the binding of a potent ligand. It is believed that deep insights into understanding the binding of hSTING with 3′3′‐CDNs and the endogenous 2′3′‐cGAMP would help to establish the principles underlying powerful 2′3′‐cGAMP signaling and the nature of hSTING activation, as well as related drug design.
Microneedle Array‐Based Platforms for Future Theranostic Applications
Authors: Howells Olivia , Rajendran Natasha , Mcintyre Sarah , Amini‐Asl Sara , Henri Pauline , Liu Yufei , Guy Owen , Cass Anthony E. G. , Morris May C. , Sharma Sanjiv 
Published: March 2019

AbstractTheranostics involves finding the biomarkers of a disease, fighting them through site specific drug delivery and following them for prognosis of the disease. Microneedle array technology has been used for drug delivery and extended for continuous monitoring of analytes present in the skin compartment. We envisage the use of microneedle arrays for future theranostic applications. The potential of combining microneedle array‐based drug delivery and diagnostics as part of closed‐loop control system for the management of diseases and delivery of precision drugs in individual patients is reported in this paper.
Long‐term impact of diabetes in patients with ST‐segment elevation myocardial infarction: Insights from the EXAMINATION randomized trial
Authors: Jimenez‐Quevedo Pilar , Brugaletta Salvatore , Cequier Angel , Iñiguez Andrés , Serra Antonio , Mainar Vicente , Campo Gianluca , Tespili Maurizio , Nombela‐Franco Luis , del Trigo Maria , Gonzalo Nieves , Escaned Javier , Salinas Pablo , Nuñez‐Gil Ivan , Fernandez‐Perez Cristina , Fernández‐Ortiz Antonio , Macaya Carlos , Serruys Patrick W. , Sabate Tenas Manel 
Published: March 2019

AbstractBackgroundLong‐term outcomes of diabetic patients suffering from ST‐segment elevation myocardial infarction (STEMI) and treated with second‐generation drug‐eluting stent have been scarcely evaluated. The aim of this posthoc subanalysis of the EXAMINATION trial was to compare 5‐year outcomes according to the presence of diabetes mellitus.MethodsFrom a total of 1,497 patients included in the trial, 258 were diabetics (n = 137, received everolimus‐eluting stent (EES) and n = 121 bare‐metal stent (BMS); whereas 1,239 were nondiabetics (n = 613 treated with EES and n = 626 with BMS). Patient‐oriented combined endpoint (POCE) defined as all‐cause death, any MI or any revascularization, and other clinical parameters were collected up to 5‐years. All results were adjusted for various potential confounders.ResultsAt 5‐years, patients with diabetes showed similar rates of POCE between diabetics treated with EES and those treated with BMS (32.8% vs. 32.2%; p = 0.88). However, rates of TLR were significantly lower in the EES group (4.4% vs. 9.9%; HR 0.52 (0.29–0.94); P = 0.03). In non‐diabetics, the use of EES was associated with a significant improvement in all‐clinical parameters except for MI rate: POCE: [10.0% vs. 12.6%; HR 0.78(0.62–0.98); P = 0.038], all cause death: [7.0% vs. 12.1%; HR 0.62(0.42–0.90); P = 0.014], and [TLR: 4.2 vs. 6.7; HR 0.60 (0.37–0.98); P = 0.04]. Overall, diabetics showed higher rate of POCE at 5‐years (32.6% vs. 21.5% in nondiabetics HR1.45[1.03–2.04];p = 0.03) driven by increased rates of MI and the need for revascularization that occurred in coronary segments remote from target lesions [2.7% vs. 1.1%; HR: 2.27 (1.12–5.23); P = 0.02 and 14% vs. 6.2%; HR: 2.11 (1.38–3.22); P = 0.001, respectively].ConclusionsDiabetics had worse clinical outcomes than nondiabetics after STEMI mainly due to atherosclerosis progression. At 5‐years, the treatment with EES did not reduce the rate of POCE in diabetics but reduced the need for revascularization compared with BMS.
Modeling and Growth Kinetics of Antisolvent Crystallization Applied to the Pharmaceutical Industry
Authors: Kodera Takanori , Kobari Masanori , Hirasawa Izumi 
Published: March 2019

AbstractWith the aim of simulating the product crystal size, which is one of the important physical properties for active pharmaceutical ingredients, an antisolvent crystallization model is proposed, including only six experimentally determined kinetic parameters to develop a concise model. As a first step, the methodology to assess the growth rate parameters, which are some of the six kinetic parameters, is discussed. An approach for appropriately treating the size distribution data obtained by means of the laser diffraction/scattering method is suggested. The determined growth rate parameters could be used to simulate the crystal size indicating that the simulation by crystallization modeling is a practical application for the pharmaceutical industry.
Theoretical Investigation of the Topology of Spiroborate‐Linked Ionic Covalent Organic Frameworks (ICOFs)
Authors: Zhang Xiaomin , Li Wenliang , Guan Yiran , Zhou Baolei , Zhang Jingping 
Published: March 2019

AbstractA novel type of ionic covalent organic framework (ICOF) with a spiroborate linkage has been recently designed and synthesized by Zhang and co‐workers (Ionic Covalent Organic Frameworks with Spiroborate Linkage, Angew. Chem. Int. Ed. 2016, 55, 1737–1741). The spiroborate‐linked ICOFs exhibit high Brunauer–Emmett–Teller (BET) surface areas and significant amounts of H2 and CH4 uptakes, combined with excellent thermal and chemical stabilities. Inspired by the novel properties of ICOFs, with the aim of gaining better understanding of the structure of such spiroborate‐linked ICOFs, a series of potential 3D network configurations of ICOFs connected with tetrahedral [BO4]− nodes were proposed, assuming the [BO4]− node in spiroborate segments takes a tetrahedral configuration. These ICOFs, in terms of 2D and 3D topology through torsional energy of the [BO4]− fragment, pore‐size distribution, total energy of the framework, and gas adsorption properties were compared and systematically investigated by density functional theory calculations, molecular mechanics, and well‐established Grand canonical Monte Carlo simulations. The results indicate that spiroborate‐linked ICOFs are likely a mixture of various topologies. Among these architectures, the five‐fold interpenetrating model shows the lowest energy and reasonable gas uptakes, therefore, it is considered to be the most possible structure. More importantly, the five‐fold interpenetrating model, showing high CH4 uptakes compared with several classic porous materials, represents a promising CH4 storage material.
Diastereodivergent Synthesis of Hexahydro‐6H‐benzo[c]chromen‐6‐one Derivatives Catalyzed by Modularly Designed Organocatalysts
Authors: Jakkampudi Satish , Parella Ramarao , Arman Hadi D. , Zhao John C.‐G. 
Published: March 2019

AbstractThe diastereodivergent synthesis of hexahydro‐6H‐benzo[c]chromen‐6‐one derivatives with good to high diastereoselectivities (up to 98:2 d.r.) and enantioselectivities (up to >99 % ee) has been achieved by using a domino Michael/Michael/hemiacetalization reaction between trans‐2‐hydroxy‐β‐nitrostyrenes and trans‐7‐oxo‐5‐heptenals followed by oxidation. With use of appropriate modularly designed organocatalysts (MDOs) that are self‐assembled in situ from amino acid derivatives and cinchona alkaloid derivatives, two different diastereomers of the desired hexahydro‐6H‐benzo[c]chromen‐6‐ones are obtained from the same substrates.
A New Insight into the Stereoelectronic Control of the Pd0‐Catalyzed Allylic Substitution: Application for the Synthesis of Multisubstituted Pyran‐2‐ones via an Unusual 1,3‐Transposition
Authors: Brůža Zbyněk , Kratochvíl Jiří , Harvey Jeremy N. , Rulíšek Lubomír , Nováková Lucie , Maříková Jana , Kuneš Jiří , Kočovský Pavel , Pour Milan 
Published: March 2019

AbstractPyran‐2‐ones 3 undergo a novel Pd0‐catalyzed 1,3‐rearrangement to afford isomers 6. The reaction proceeds via an η2‐Pd complex, the pyramidalization of which (confirmed by quantum chemistry calculations) offers a favorable antiperiplanar alignment of the Pd−C and allylic C−O bonds (C), thus allowing the formation of an η3‐Pd intermediate. Subsequent rotation and rate‐limiting recombination with the carboxylate arm then gives isomeric pyran‐2‐ones 6. The calculated free energies reproduce the observed kinetics semi‐quantitatively.
AuPt Bipyramid Nanoframes as Multifunctional Platforms for In Situ Monitoring of the Reduction of Nitrobenzene and Enhanced Electrocatalytic Methanol Oxidation
Authors: Fang Caihong , Zhao Guili , Zhang Zijun , Ding Qian , Yu Nan , Cui Zhiqing , Bi Ting 
Published: March 2019

AbstractMultifunctional metal nanostructures with a hollow feature, especially for nanoframes, are highly attractive owing to their high surface‐to‐volume ratios. However, pre‐grown metal nanocrystals are always involved during the preparation procedure, and a synthetic strategy without the use of a pre‐grown template is still a challenge. In this article, a template‐free strategy is reported for the preparation of novel AuPt alloy nanoframes through simply mixing HAuCl4 and H2PtCl6 under mild conditions. The alloy nanostructures show a bipyramid‐frame hollow architecture with the existence of only the ten ridges and absence of their side faces. This is the first report of bipyramid‐like nanoframes and a template‐free method under mild conditions. This configuration merges the plasmonic features of Au and highly active catalytic sites of Pt in a single nanostructure, making it an ideal multifunctional platform for catalyzing and monitoring the catalytic reaction in real time. The superior catalytic activity is demonstrated by using the reduction of nitrobenzene to the corresponding aminobenzene as a model reaction. More importantly, the AuPt nanoframes can track the reduction process on the basis of the SERS signals of the reactants, intermediates, and products, which helps to reveal the reaction mechanism. In addition, the AuPt nanoframes show much higher electrocatalytic properties toward the methanol oxidation reaction than commercial Pt/C electrocatalysts.
Lanthanum‐Catalyzed Enantioselective Trifluoromethylation by Using an Electrophilic Hypervalent Iodine Reagent
Authors: Granados Albert , Rivilla Iván , Cossío Fernando P. , Vallribera Adelina 
Published: March 2019

AbstractA highly enantioselective catalytic method for the synthesis of quaternary α‐trifluoromethyl derivatives of 3‐oxo esters is described. The reaction uses lanthanum(III) triflate and chiral PyBOX‐type C2‐symmetric ligands to generate intermediate LaIII complexes that incorporate an enolate moiety of the starting 3‐oxo ester and the trifluoromethylation transfer reagent. The enantioselectivity of the reaction stems from the efficient blockage of one of the prochiral faces of the LaIII enolate by one unit of the C2‐symmetric ligand.
Prognostic implications of troponin I elevation in emergency department patients with tachyarrhythmia
Authors: González‐Del‐Hoyo Maribel , Cediel Germán , Carrasquer Anna , Bonet Gil , Vásquez‐Nuñez Karla , Boqué Carme , Alí Samuel , Bardají Alfredo 
Published: March 2019

BackgroundTachyarrhythmias are very common in emergency medicine, and little is known about the long‐term prognostic implications of troponin I levels in these patients.HypothesisThis study aimed to investigate the correlation of cardiac troponin I (cTnI) levels and long‐term prognosis in patients admitted to the emergency department (ED) with a primary diagnosis of tachyarrhythmia.MethodsA retrospective cohort study was conducted between January 2012 and December 2013, enrolling patients admitted to the ED with a primary diagnosis of tachyarrhythmia and having documented cTnI measurements. Clinical characteristics and 5‐year all‐cause mortality were analyzed.ResultsOf a total of 222 subjects with a primary diagnosis of tachyarrhythmia, 73 patients had elevated levels of cTnI (32.9%). Patients with elevated cTnI levels were older and presented significantly more cardiovascular risk factors. At the 5‐year follow‐up, mortality was higher among patients with elevated cTnI levels (log‐rank test P < 0.001). In the multivariable Cox regression analysis, elevated cTnI was an independent predictor of all‐cause death (hazard ratio, 1.95, 95% confidence interval: 1.08‐3.50, P = 0.026), in addition to age and prior heart failure.ConclusionPatients admitted to the ED with a primary diagnosis of tachyarrhythmia and high cTnI levels have higher long‐term mortality rates than patients with low cTnI levels. cTnI is thus a biomarker with predictive capacity for mortality in late follow‐up, conferring utility in the risk stratification of this population.
A Study of the Direct Spectral Transform for the Defocusing Davey‐Stewartson II Equation the Semiclassical Limit
Authors: Assainova O. , Klein C. , McLaughlin K. D. T.‐R. , Miller P. D. 
Published: March 2019

AbstractThe defocusing Davey‐Stewartson II equation has been shown in numerical experiments to exhibit behavior in the semiclassical limit that qualitatively resembles that of its one‐dimensional reduction, the defocusing nonlinear Schrödinger equation, namely the generation from smooth initial data of regular rapid oscillations occupying domains of space‐time that become well‐defined in the limit.As a first step to studying this problem analytically using the inverse scattering transform, we consider the direct spectral transform for the defocusing Davey‐Stewartson II equation for smooth initial data in the semiclassical limit. The direct spectral transform involves a singularly perturbed elliptic Dirac system in two dimensions. We introduce a WKB‐type method for this problem, proving that it makes sense formally for sufficiently large values of the spectral parameter k by controlling the solution of an associated nonlinear eikonal problem, and we give numerical evidence that the method is accurate for such k in the semiclassical limit. Producing this evidence requires both the numerical solution of the singularly perturbed Dirac system and the numerical solution of the eikonal problem. The former is carried out using a method previously developed by two of the authors, and we give in this paper a new method for the numerical solution of the eikonal problem valid for sufficiently large k.For a particular potential we are able to solve the eikonal problem in closed form for all k, a calculation that yields some insight into the failure of the WKB method for smaller values of k. Informed by numerical calculations of the direct spectral transform, we then begin a study of the singularly perturbed Dirac system for values of k so small that there is no global solution of the eikonal problem. We provide a rigorous semiclassical analysis of the solution for real radial potentials at k=0, which yields an asymptotic formula for the reflection coefficient at k=0 and suggests an annular structure for the solution that may be exploited when k ≠ 0 is small. The numerics also suggest that for some potentials the reflection coefficient converges pointwise as ɛ↓ 0 to a limiting function that is supported in the domain of k‐values on which the eikonal problem does not have a global solution. It is expected that singularities of the eikonal function play a role similar to that of turning points in the one‐dimensional theory. © 2019 Wiley Periodicals, Inc.
A Trigonal Prismatic Cobalt(II) Complex as a Single Molecule Magnet with a Reduced Contribution from Quantum Tunneling
Authors: Pavlov Alexander A. , Aleshin Dmitry Y. , Savkina Svetlana A. , Belov Alexander S. , Efimov Nikolay N. , Nehrkorn Joscha , Ozerov Mykhaylo , Voloshin Yan Z. , Nelyubina Yulia V. , Novikov Valentin V. 
Published: March 2019

AbstractHerein, we report a new trigonal prismatic cobalt(II) complex that behaves as a single molecule magnet. The obtained zero‐field splitting, which is also directly accessed by THz‐EPR spectroscopy (−102.5 cm−1), results in a large magnetization reversal barrier U of 205 cm−1. Its effective value, however, is much lower (101 cm−1), even though there is practically no contribution from quantum tunneling to magnetization relaxation.
Graphene‐Encapsulated Co9S8 Nanoparticles on N,S‐Codoped Carbon Nanotubes: An Efficient Bifunctional Oxygen Electrocatalyst
Authors: Jia Nan , Liu Jing , Gao Yunshan , Chen Pei , Chen Xinbing , An Zhongwei , Li Xifei , Chen Yu 
Published: March 2019

AbstractAn inexpensive and efficient bifunctional electrocatalyst for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is central to the rechargeable zinc–air battery. Herein, a nanohybrid, in which N,S‐codoped carbon nanotubes were decorated with Co9S8 nanoparticles encapsulated in porous graphene layers, was fabricated by a one‐step heat‐treatment process. The N,S dopant species were the major active sites for the ORR, and Co9S8 nanoparticles were mainly responsible for the OER. Compared with commercial 20 wt % Pt/C and Ir/C electrocatalysts, this nanohybrid exhibited a comparable ORR half‐wave potential (0.831 V vs. reversible hydrogen electrode) and OER potential (1.591 V at 10 mA cm−2), better long‐term stability in an alkaline medium, and a narrower potential gap (0.76 V) between ORR and OER. Furthermore, as air electrode of the rechargeable zinc–air battery, it delivered a low charge–discharge voltage gap (0.65 V at 5 mA cm−2), high open‐circuit potential (1.539 V), good specific capacity (805 mA h g
at 5 mA cm−2), and excellent cycling stability (48 h), superior to those of commercial Pt/C and Ir/C catalysts, and thus showed promise for applications in renewable energy conversion devices.
Highly Stable and High Rate‐Performance Na‐Ion Batteries Using Polyanionic Anthraquinone as the Organic Cathode
Authors: Tang Wu , Liang Ren , Li Di , Yu Qihang , Hu Jiahui , Cao Bei , Fan Cong 
Published: March 2019

AbstractSodium 9,10‐anthraquinone‐2,6‐disulfonate (Na2AQ26DS), with polyanionic character and two O−Na ionic bonds, is found to be a highly stable organic cathode in Na‐ion batteries, delivering capacities of approximately 120 mAh g−1 for 300 cycles (50 mA g−1) and around 99 mAh g−1 for 1000 cycles (1 A g−1). These results are the best performance reported to date for small‐molecule, anthraquinone‐based organic cathodes in Li‐, Na‐, or K‐ion batteries.
Imidazolium‐Salt‐Functionalized Covalent Organic Frameworks for Highly Efficient Catalysis of CO2 Conversion
Authors: Qiu Jikuan , Zhao Yuling , Li Zhiyong , Wang Huiyong , Shi Yunlei , Wang Jianji 
Published: March 2019

AbstractThe conversion of CO2 into valuable chemicals is an ideal pathway for CO2 utilization in industry, although the development of highly efficient catalysts remains a challenge. Herein, the design and synthesis of two covalent organic frameworks (COFs) functionalized with imidazolium salts were reported as catalysts for CO2 conversion. The resultant COFs possessed highly crystalline structures, showed high stability and surface area, and contained dense catalytic active sites on the pore walls. They exhibited outstanding catalytic performances for the reaction of CO2 with epoxides without any solvent or cocatalyst under mild conditions and afforded a record turnover number of 495 000. In addition, the COFs could serve as effective catalysts in the reductive reaction of CO2 with amines. The results presented here thus demonstrate the exceptional potential of the functionalized COFs for various challenging CO2 transformations.
Prevalence of high‐risk HPV and atypia in liquid‐based cytology of cervical and intra‐anal specimens from kidney‐transplanted women
Authors: Eleutério José , Cavalcante Liana R. , Gonçalves Ana K. S. , Eleutério Renata M. N. , Giraldo Paulo C. 
Published: March 2019

BackgroundThere is a high frequency of human papillomavirus (HPV)‐induced lesions in cervix and anus of immunosuppressed patients. However, few studies have evaluated these lesions in kidney‐transplanted women.MethodsThis cross‐sectional study examined 31 kidney‐transplanted women receiving immunosuppressive therapy at the General Hospital of Fortaleza in Brazil. Cervical and anal samples were collected and preserved in order to perform liquid‐based cytology and a real‐time polymerase chain reaction assay detecting high‐risk HPV.ResultsThe patients' ages ranged from 31 to 70 years (mean: 42.6 ± 10.4). The age of sexual debut varied from 14 to 30 years (mean: 19.7 ± 3.8). Cervical cytology was diagnosed as atypical in 25.8% of cases (atypical squamous cells of undetermined significance [ASC‐US] in 2 [6.2%], atypical squamous cells, but unable to exclude a high‐grade squamous intraepithelial lesion in 1 [3.1%], low‐grade squamous intraepithelial lesion [LSIL] in 4 [12.4%], and squamous cell carcinoma in 1 [3.1%]). Anal cytology was atypical in 35.4% of cases (ASC‐US in 1 [3.2%] and LSIL in 7 [21.7%]). The presence of cervical HPV was confirmed in 22.5% of patients, and anal HPV was found in 48.8% of the cases. The relative risk of atypical anal cytology in cases of atypical cervical cytology was 4.37 (1.35‐14.20). High‐risk cervical HPV did not significantly increase the risk of having atypical anal cytology. However, for HPV in the anus, this was associated with a relative risk of 10.18 (1.45‐71.54).ConclusionHigh‐risk HPV and atypical cytology are very common in the cervix and anus of kidney‐transplanted women. Furthermore, the presence of HPV in an anal sample correlates with an increased risk of atypical anal cytology. HPV tests could be useful tools for identifying patients who require anal cytology.
Human Biospecimens Come from People
Authors: Tomlinson Tom , De Vries Raymond G. 
Published: March 2019

ABSTRACTContrary to the revised Common Rule, and contrary to the views of many bioethicists and researchers, we argue that broad consent should be sought for anticipated later research uses of deidentified biospecimens and health information collected during medical care. Individuals differ in the kinds of risk they find concerning and in their willingness to permit use of their biospecimens for future research. For this reason, asking their permission for unspecified research uses is a fundamental expression of respect for them as persons and should be done absent some compelling moral consideration to the contrary. We examine three moral considerations and argue that each of them fails: that there is a duty of easy rescue binding on all, that seeking consent creates a selection bias that undermines the validity of biospecimen research, and that seeking and documenting consent will be prohibitively expensive.