bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twofold C−H Activation‐Based Enantio‐ and Diastereoselective C−H Arylation Using Diarylacetylenes as Rare Arylating Reagents
Authors: Hu Panjie , Kong Lingheng , Wang Fen , Zhu Xiaolin , Li Xingwei 
Published: June 2021

AbstractC−H bond activation has been established as an attractive strategy to access axially chiral biaryls, and the most straightforward method is direct C−H arylation of arenes. However, the arylating source has been limited to several classes of reactive and bulky reagents. Reported herein is rhodium‐catalyzed 1:2 coupling of diarylphosphinic amides and diarylacetylenes for enantio‐ and diastereoselective construction of biaryls with both central and axial chirality. This twofold C−H activation reaction stays contrast to the previously explored Miura–Satoh type 1:2 coupling of arenes and alkynes in terms of chemoselectivity and proceeded under mild conditions with the alkyne acting as a rare arylating reagent. Both C−H activation events are stereo‐determining and are under catalyst control, with the 2ndC−H activation being diastereo‐determining in a remote fashion. Analysis of the stereochemistry of the major and side products suggests moderate enantioselectivity of the initial C−H activation–desymmetrization process. However, the minor (R) rhodium vinyl intermediate is consumed more readily in undesired protonolysis, eventually resulting in high enantio‐ and diastereoselectivity of the major product.
Monitoring Metabolites Using an NAD(P)H‐sensitive Polymer Dot and a Metabolite‐Specific Enzyme
Authors: Chen Haobin , Yu Jiangbo , Zhang Jicheng , Sun Kai , Ding Zhaoyang , Jiang Yifei , Hu Qiongzheng , Wu Changfeng , Chiu Daniel T. 
Published: June 2021

AbstractWe introduce an NAD(P)H‐sensitive polymer dot (Pdot) biosensor for point‐of‐care monitoring of metabolites. The Pdot is combined with a metabolite‐specific NAD(P)H‐dependent enzyme that catalyzes the oxidation of the metabolite, generating NAD(P)H. Upon UV illumination, the NAD(P)H quenches the fluorescence emission of Pdot at 627 nm via electron transfer, and also fluoresces at 458 nm, resulting in a shift from red to blue emission at higher NAD(P)H concentrations. Metabolite concentration is quantified ratiometrically‐based on the ratio of blue‐to‐red channel emission intensities, with a digital camera‐with high sensitivity and specificity. We demonstrate phenylalanine biosensing in human plasma for a phenylketonuria screening test, quantifying several other disease‐related metabolites (lactate, glucose, glutamate, and β‐hydroxybutyrate), and a paper‐based assay with smartphore imaging for point‐of‐care use.
Wiggling Mesopores Kinetically Amplify the Adsorptive Separation of Propylene/Propane
Authors: Yuan Ya‐Fei , Wang Yong‐Sheng , Zhang Xue‐Liang , Li Wen‐Cui , Hao Guang‐Ping , Han Lu , Lu An‐Hui 
Published: June 2021

AbstractAdsorptive separation is an appealing technology for propylene and propane separation; however, the challenge lies in the design of efficient adsorbents which can distinguish the two molecules having very similar properties. Here we report a kinetically amplified separation by creating wiggling mesopores in structurally robust carbon monoliths. The wiggling mesopores with alternating wide and narrow segments afford a surface area of 413 m2 g−1and a tri‐modal pore size distribution centered at 1.5, 4.2 and 6.6 nm, respectively. The synergistically kinetic and equilibrium effects were observed and quantitatively assessed, which together ensured a remarkable propylene/propane selectivity up to 39. This selectivity outperformed not only the available carbon adsorbents but also highly competitive among the dominated crystalline porous adsorbents. In addition, the wiggling mesoporous carbon adsorbent showed excellent dynamical separation stability, which ensured its great potential in practical molecular separations.
Endothelial ontogeny and the establishment of vascular heterogeneity
Authors: Stone Oliver A. , Zhou Bin , Red‐Horse Kristy , Stainier Didier Y.R. 
Published: June 2021

AbstractThe establishment of distinct cellular identities was pivotal during the evolution of Metazoa, enabling the emergence of an array of specialized tissues with different functions. In most animals including vertebrates, cell specialization occurs in response to a combination of intrinsic (e.g., cellular ontogeny) and extrinsic (e.g., local environment) factors that drive the acquisition of unique characteristics at the single‐cell level. The first functional organ system to form in vertebrates is the cardiovascular system, which is lined by a network of endothelial cells whose organ‐specific characteristics have long been recognized. Recent genetic analyses at the single‐cell level have revealed that heterogeneity exists not only at the organ level but also between neighboring endothelial cells. Thus, how endothelial heterogeneity is established has become a key question in vascular biology. Drawing upon evidence from multiple organ systems, here we will discuss the role that lineage history may play in establishing endothelial heterogeneity.
Tailoring of thermoluminescent properties and assessment of trapping parameters of natural fluorite samples from Dogargaon fluorite mines, India
Authors: Randive Kirtikumar , Jawadand Sanjeevani , Dora M. L. , Kadam Abhijeet R. , Dhoble S. J. 
Published: June 2021

AbstractMineral fluorite or fluorspar (CaF2) can host significant quantities of trivalent REE3+ (rare earth element) by substitution with divalent Ca2+. The fluorites associated with carbonatites are often REE‐rich compared to those derived from sedimentary, hydrothermal, or Mississippi Valley‐type (MVT) fluorites. The naturally occurring fluorites have several industrial applications one of which is for luminescence. Whether or not REE enriched, the fluorite makes an ideal host for REEs, which are very important phosphors. The naturally occurring fluorites are available in sufficient quantities to cater to the industrial demand. Investigations have been carried out on the fluorites from active fluorite mines at Dongargaon in central India. Thermoluminescence behavior of a natural fluorite sample was investigated using a Nucleonix TL 1009I thermoluminescence reader. Multiple traps formed in the broad thermoluminescent (TL) glow curve were found by TL anal deconvolution software. Trapping parameters for all multiple traps formed on deconvoluting broad TL glow curve were found by different methods like Initial rise method, Chen's Peak shape method and Ilich method.
Synchronized determination of sacubitril and valsartan with some co‐administered drugs in human plasma via UPLC–MS/MS method using solid‐phase extraction
Authors: Moussa Bahia Abbas , Hashem Hanaa M. A. , Mahrouse Marianne Alphonse , Mahmoud Sally Tarek 
Published: June 2021

AbstractAn accurate and sensitive UPLC–MS/MS method was developed and validated for the simultaneous estimation of the newly developed combination of sacubitril and valsartan and the co‐administered drugs nebivolol, chlorthalidone and esomeprazole in human plasma. Solid‐phase extraction was conducted for the purification and extraction of the drugs from human plasma. Chromatographic separation was carried out on an Agilent SB‐C18 (1.8 μm, 2.1 × 50 mm) column using losartan as internal standard. Isocratic elution was applied using acetonitrile–0.1% formic acid in water (85: 15, v/v) as mobile phase. Detection was carried out using a triple‐quadrupole tandem mass spectrometer using multiple reaction monitoring, at positive mode at m/z 412.23 → 266.19 for sacubitril, m/z 436.29 → 235.19 for valsartan, m/z 405.8 → 150.98 for nebivolol, m/z 346.09 → 198 for esomeprazole and a selected combination of two fragments m/z 423.19 → 207.14 and 423.19 → 192.2 for losartan (internal standard), and in negative ionization mode at m/z 337.02 → 190.12 for chlorthalidone. The method was linear over the concentration ranges 30–2,000 ng/ml for sacubitril, 70–2,000 ng/ml for valsartan, esomeprazole and chlorthalidone and 70–5,000 pg/ml for nebivolol. The developed method is sensitive and selective and could be applied for dose adjustment, bioavailability and drug–drug interaction studies.
The effect of non‐directive play therapy on reduction of anxiety disorders in young children
Authors: Hateli Bahare 
Published: June 2021

AbstractBackgroundThere is strong evidence that non‐directive play therapy, which is also known as child‐centred play, may be useful in reducing anxiety in young children. Non‐directive play is an approach to playing where the child is given ultimate freedom rather than a practitioner impressing ideas on them.ObjectivesThe purpose of this study was to evaluate the efficacy of non‐directive play therapy for anxiety reduction in children.MethodsFor this purpose, 20 elementary students who had been diagnosed as anxious according to the Spence Children's Anxiety Scale (SCAS) were selected through random sampling and were divided into an experimental group and control group. The experimental group participated in 10 sessions of play therapy, and after finishing the sessions, the SCAS questionnaire was implemented again as a post‐test. Analysis of covariance was used to analyse the data.ResultsThe results of the study showed that scores on the anxiety scale reduced significantly in the experimental group.ConclusionsNon‐directive play therapy was useful in reducing children's anxiety, so it may be implicated as an education plan for problematic parent–child relationships. However, more studies are needed to support these results.
What support do therapists need to do research? A review of studies into how therapists experience research
Authors: Bager‐Charleson Sofie , McBeath Alistair G. 
Published: June 2021

AbstractThis paper addresses therapists’ experiences when ‘doing research’, with a special interest in their needs for support. It involves revisiting earlier studies into opportunities and obstacles—personally, professionally and academically for psychotherapists and counselling psychologists (therapists) when transitioning to and from postgraduate research. How do therapists experience research; what motivates them to undertake doctoral research; how do they chose to generate knowledge and why; and how will expectations meet outcomes? This ‘re‐search’ approaches earlier studies with an interest in research support. It highlights significant personal, professional and academic obstacles for therapists transitioning into research. Shame, isolation and poor opportunities to research and engage on academic platforms are some of the areas being referred to. Consistent with such needs, our pilot study into research supervision showed how supervisees rated ‘empathy’ as highly as ‘research experience’ for ‘constructive’ supervision. Our review involves a ‘hybrid meta‐synthesis’ that combines autoethnographic and secondary analysis aims. It draws on personal experience of grappling with methodological options as examples of how mixed methods study may ‘come about’ or develop as part of team research practice.
Are Child Welfare Intervention Rates Higher or Lower in Areas Targeted for Enhanced Early Years Services?
Authors: Scourfield Jonathan , Webb Calum J. R. , Elliott Martin , Staniland Lydia , Bywaters Paul 
Published: June 2021

Flying Start is an enhanced early years programme in Wales which is targeted at areas where a high proportion of households with children are recipients of income‐related benefits or tax credits. Child protection interventions are known to be concentrated in more deprived areas. Flying Start could have the effect of reducing risk to children or, conversely, it could result in more children coming to the attention of social services. Administrative data were used to identify children in public care and on child protection registers in Wales on 31 March 2015 and to identify lower super output areas covered by Flying Start services. Child welfare intervention rates were examined, and a comparison was made between areas within deprivation quintiles where Flying Start was operating and areas where it was not. In areas where Flying Start services are provided, child welfare intervention rates are higher than in areas where they are not, after controlling for multiple deprivation. Further work is needed to establish why child welfare intervention rates are higher in Flying Start areas and what effect there might be longer term.‘Child welfare intervention rates were examined, and a comparison was made between areas… where Flying Start was operating and areas where it was not’Key Practitioner Messages

In Wales there is a ‘social gradient’ in the rates at which local authorities intervene by placing children in statutory care or making them subject to child protection procedures. For each increase in relative deprivation, there is a corresponding increase in intervention rates.
In areas where Flying Start enhanced early years services are provided, child welfare intervention rates are higher than in areas where they are not, after controlling for area‐level deprivation.
The link between poverty and risk to children needs to be more clearly acknowledged in the child protection process.
Key steps to reduce the aerosolized risk related to total laryngectomy in COVID‐19 era: A case report
Authors: Chessman Robert , Singh Tahwinder , Passley Davinia , Gande Richard , Konieczny Katarzyna , Patel Nimesh N. 
Published: June 2021

AbstractLaryngectomy surgery is a highly aerosolizing procedure, and we document the key steps, including the addition of a novel Perspex shield, which can be enacted during the COVID‐19 pandemic to reduce risk to the patient and healthcare professional.
Heat recovery from hydrothermal carbonization slurry product by coupling processes of flash and organic Rankine cycle: Thermodynamic analysis
Authors: Jia Jiandong , Chen Hongwei , Wang Ruikun , Zhao Zhenghui , Ren Daomeng , Liu Hantao , Lei Haoyang 
Published: June 2021

AbstractHydrothermal carbonization (HTC) is a promising and effective technology for upgrading the fuel quality of high‐moisture organic wastes. However, a large amount of energy is required to heat the feedstock to high temperature for HTC. Therefore, the maximum waste heat should be recovered to increase the energy efficiency of the HTC process. In this work, a flash‐organic Rankine cycle (FSPG‐ORC) system was coupled after HTC to recover the heat contained in the HTC slurry product. Various operating factors including the flashing temperature, the HTC temperature, the solid‐water ratio (S/W) of the feedstock, and the organic working fluids in the ORC section were studied to obtain their influences on thermodynamic performance of the coupled system. Results indicated that the net power (Wnet) of the FSPG‐ORC system increased from 185.64 to 774.30 kW through the increase of the HTC temperature from 160 to 280°C. In addition, the Wnet and exergy efficiency of the FSPG‐ORC system also increased with increasing the flashing temperature of HTC slurry product. The coupled FSPG‐ORC system converted waste heat to electric energy and increased the energy efficiency of the HTC process.
Dynamic Pendulum Effect of an Exceptionally Flexible Pillared‐Layer Metal‐Organic Framework†
Authors: Zhou Hao‐Long , Bai Jie , Tian Xiao‐Yun , Mo Zong‐Wen , Chen Xiao‐Ming 
Published: June 2021

Main observation and conclusionMagnifying the controllable directional motions of molecular machines to the macroscopic levels is a significant topic for chemists. Flexible metal–organic frameworks with long‐range order and responsive structural transformation under external stimuli may be an appropriate platform for achieving the target. By taking advantage of the single‐crystal to single‐crystal manner of soft porous crystals, we utilize single‐crystal X‐ray diffraction to directly observe the dynamic structural inversion of a new three‐fold interpenetrated pillared‐layer metal‐organic framework [Co(edba)(bpy)] (MCF‐83, H2edba = 4,4’‐(ethyne‐1,2‐diyl)dibenzoic acid, bpy = 4,4’‐bipyridine). More interestingly, the dynamic inversions of the pillars and layers are selectively guest‐controllable and independent, allowing precise control of the directional shape changes, which is the key of constructing intelligent materials to accomplish a complex task. The mechanism is further studied by combining the X‐ray diffraction analyses, sorption measurements and molecular simulations.
Supramolecular Polymer Networks with Enhanced Mechanical Properties: The Marriage of Covalent Polymer and Metallacycle†
Authors: Zhang Yue‐Yue , Chen Feng , Li Yang , Qiu Hua‐Yu , Zhang Jin‐Jin , Yin Shou‐Chun 
Published: June 2021

Main observation and conclusionSupramolecular polymer networks (SPNs) have always been the focus of research due to their novel features of good processability, stimuli‐responsiveness, self‐healing, and recyclability. Herein, we report the preparation of a metallacycle‐linked supramolecular gel via orthogonal metal‐ligand interactions and host‐guest interactions. A triangular metallacycle with three appended 21‐crown‐7 (21C7) units was obtained by the metal coordination of nickel(II)‐salen‐based dipyridyl ligands and platinum(II) acceptors. The integration of this metallacycle and traditional copolymer bearing secondary ammonium salts constructed a SPN via host‐guest recognition between 21C7 units and ammonium salts, and a supramolecular gel further formed at high concentration. Multiple stimulus responsiveness and self‐healing properties of gel were observed. The gel exhibited better stretchability compared to relative gel formed by copolymer alone owing to the synergistic effect of covalent bonds and supramolecular interactions. Moreover, compared to the model gel without metallacycles, the gel showed higher storage and loss moduli, and exhibited stronger stiffness in the self‐healing tests performed with rheometer, indicating the metallacycle played an important role in improving the stiffness and self‐healing of the gel. Therefore, the feasible approach to the formation of SPNs by the marriage of covalent polymers and metallacycles is expected to open a new way to design novel SPNs.
Circulating miRNAs—A potential tool to identify severe asthma risk?
Authors: Kyyaly Mohammed A. , Sanchez‐Elsner Tilman , He Peijun , Sones Collin L. , Arshad S. Hasan , Kurukulaaratchy Ramesh J. 
Published: June 2021

AbstractBackgroundIdentifying patients at risk of severe asthma is vitally important given the disproportionate burden of disease imposed by that state. However, biomarkers to support such needs remain elusive.MethodsIn this letter, we assessed whether specific panels of circulating miRNAs (microRNAs) can differentiate between mild and severe asthma patients as well as between healthy subjects and severe asthma patients.ResultsTo our knowledge, the miRNAs identified in our work such as miR‐28‐3p, miR‐16‐2‐3p, and miR‐210‐3p have not been previously reported as differentially expressed in the serum of severe asthma patients.ConclusionOur findings suggest that miRNA expression profiles may have the capability as potential biomarkers that signal the risk of having severe asthma. As such, these findings have significant novelty and merit wider dissemination to facilitate further work in this field.
Pharmacokinetic Evaluation of the CYP3A4 and CYP2D6 Drug‐Drug Interaction and CYP3A4 Induction Potential of Omecamtiv Mecarbil: Two Open‐Label Studies in Healthy Subjects
Authors: Trivedi Ashit , Malik Fady I. , Jafarinasabian Pegah , Zhang Hanze , Flach Stephen , Abbasi Siddique , Dutta Sandeep , Lee Edward 
Published: June 2021

AbstractOmecamtiv mecarbil (OM) is a cardiac myosin activator under development for the treatment of heart failure. The effect of CYP3A4 and CYP2D6 inhibition on OM pharmacokinetics and the potential for OM to induce CYP3A4 was assessed in 2 studies. Study 1, part A, assessed the effect of ketoconazole 200 mg on the pharmacokinetics of OM 10 mg in CYP2D6 extensive metabolizers (EMs; n = 8) or poor metabolizers (PMs; n = 8). Study 1, part B, assessed the effect of diltiazem 240 mg on the pharmacokinetics of OM 10 mg (EM; n = 8). Study 2 assessed the effect of OM 25 mg on the pharmacokinetics of midazolam 5 mg (n = 14). Coadministration with ketoconazole led to 51% and 31% increases in OM AUCinf in EM and PM subjects, respectively, whereas OM Cmax remained similar (3% higher and 14% lower for EM and PM subjects, respectively). No changes in OM pharmacokinetics were observed in EM subjects following coadministration with diltiazem. Midazolam AUCinf and Cmax decreased by 18% and 10%, respectively, when coadministered with OM. In conclusion, CYP3A4 and CYP2D6 inhibitors are unlikely to have a clinically significant effect on the pharmacokinetics of OM. In addition, OM is unlikely to have a clinically relevant effect on the pharmacokinetics of CYP3A4 substrates.
Assessment of the Effect of Pyrimethamine, a Potent Inhibitor of Multidrug and Toxin Extrusion Protein 1/2K, on the Pharmacokinetics of Gefapixant (MK‐7264), a P2X3 Receptor Antagonist
Authors: Nussbaum Jesse C. , Hussain Azher , Ma Bennett , Min K. Chris , Evers Raymond , Li Yun , Garrett Graigory , Stoch S. Aubrey , Iwamoto Marian 
Published: June 2021

AbstractGefapixant (MK‐7264, AF‐219) is a first‐in‐class P2X3 antagonist in development for refractory or unexplained chronic cough. Gefapixant is primarily cleared by renal excretion. To assess the importance of the multidrug and toxin extrusion protein 1 (MATE1) and MATE2K transporters in the elimination of gefapixant, a drug‐drug interaction study was conducted evaluating the effect of coadministration of a single dose of pyrimethamine, a competitive inhibitor of MATE1 and MATE2K, on the single‐dose pharmacokinetics of gefapixant in healthy participants. Safety and tolerability were also assessed. In this open‐label, 2‐period, fixed‐sequence study, a 45‐mg dose of gefapixant was administered to 12 participants in period 1. After a 7‐day washout, a 50‐mg dose of pyrimethamine was administered 3 hours before a 45‐mg dose of gefapixant in period 2. Compared with the administration of gefapixant alone, concomitant dosing of gefapixant with pyrimethamine increased the total gefapixant plasma exposure (area under the plasma concentration–time curve from time 0 to infinity) by 24%, reduced gefapixant renal clearance by 30%, and increased gefapixant mean terminal half‐life from 7.7 to 10.3 hours. The most frequently reported adverse events were dysgeusia, hypogeusia, and dry mouth; all adverse events were considered of mild intensity and resolved by the end of the study. These results support that MATE1 and/or MATE2K contribute to the renal clearance of gefapixant, but the effect of inhibition of these transporters on gefapixant pharmacokinetics is not considered clinically meaningful.
Synthesis, Characterization, and Properties of Rivaroxaban New Crystalline Forms
Authors: Zhai Lihai , Zhang Zhaohua , Guo Lihong , Zhu Zhiying , Hu Changkai , Zhang Guimin 
Published: June 2021

AbstractIn this paper, two new Rivaroxaban crystalline forms are reported and characterized by the single‐crystal X‐ray diffraction (SXRD), powder X‐ray diffraction (PXRD), thermogravimetric analysis, and differential scanning calorimetry (TGA/DSC), which are synthesized with formic acid and acetic acid, named as forms F and G, respectively. The intermolecular forces for forms F and G are analyzed by Hirshfeld surface analysis method, showing that the force of O···H is significantly stronger than that of H···H. Furthermore, the stability, solubility, and bioavailability of the two crystal forms are also studied. The clinical experiments show that form F is more effective than other reported crystal forms in inhibiting the activity of thrombin and thrombosis, which is expected to replace the marketed crystalline forms in clinical application.