bluuebunny/crossref_metadata_2025 huggingface dataset:
Homologisierung der Fischer‐Indol‐Synthese: Chinoline via Homo‐Diaza‐Cope‐Umlagerung
Authors: Gerosa Gabriela Guillermina , Schwengers Sebastian Armin , Maji Rajat , De Chandra Kanta , List Benjamin
Published: July 2020

Wir beschreiben eine neuartige Strategie zur Synthese von Chinolinen basierend auf einer Brønsted‐Säure‐induzierten Homo‐Diaza‐Cope‐Umlagerung von N‐Aryl‐N′‐Cyclopropylhydrazinen. Unsere Strategie kann als Homologisierung der klassischen Fischer‐Indol‐Synthese verstanden werden und ermöglicht die Bildung sechsgliedriger N‐Heterocyclen inklusive weiterer, vorher nicht zugänglicher Pyridinderivate. Außerdem kann die Methode als Pyridanellierungsstrategie zur Herstellung polycyclischer Polyheteroaromaten verwendet werden. Theoretische Berechnungen wurden zum Verständnis plausibler Aktivierungsmodi sowie des Einflusses des Katalysators herangezogen.
Heterogeneous Electrofreezing Triggered by CO2 on Pyroelectric Crystals: Qualitatively Different Icing on Hydrophilic and Hydrophobic Surfaces
Authors: Curland Sofia , Javitt Leah , Weissbuch Isabelle , Ehre David , Lahav Meir , Lubomirsky Igor
Published: July 2020

By performing icing experiments on hydrophilic and hydrophobic surfaces of pyroelectric amino acids and on the x‐cut faces of LiTaO3, we discovered that the effect of electrofreezing of super cooled water is triggered by ions of carbonic acid. During the cooling of the hydrophilic pyroelectric crystals, a continuous water layer is created between the charged hemihedral faces, as confirmed by impedance measurements. As a result, a current of carbonic acid ions, produced by dissolved environmental CO2, flows through the wetted layer towards the hemihedral faces and elevates the icing temperature. This proposed mechanism is based on the following: (i) on hydrophilic surfaces, water with dissolved CO2 (pH 4) freezes at higher temperatures than pure water of pH 7. (ii) In the absence of the ionic current, achieved by linking the two hemihedral faces of hydrophilic crystals by a conductive paint, water of the two pH levels freeze at the same temperature. (iii) On hydrophobic crystals with similar pyroelectric coefficients, where there is no continuous wetted layer, no electrofreezing effect is observed.
Atomic Imaging of Subsurface Interstitial Hydrogen and Insights into Surface Reactivity of Palladium Hydrides
Authors: Lin Bingqing , Wu Xi , Xie Lin , Kang Yongqiang , Du Hongda , Kang Feiyu , Li Jia , Gan Lin
Published: July 2020

Resolving interstitial hydrogen atoms at the surfaces and interfaces is crucial for understanding the mechanical and physicochemical properties of metal hydrides. Although palladium (Pd) hydrides hold important applications in hydrogen storage and electrocatalysis, the atomic position of interstitial hydrogen at Pd hydride near surfaces still remains undetermined. We report the first direct imaging of subsurface hydrogen atoms absorbed in Pd nanoparticles by using differentiated and integrated differential phase contrast within an aberration‐corrected scanning transmission electron microscope. In contrast to the well‐established octahedral interstitial sites for hydrogen in the bulk, subsurface hydrogen atoms are directly identified to occupy the tetrahedral interstices. DFT calculations show that the amount and the occupation type of subsurface hydrogen atoms play an indispensable role in fine‐tuning the electronic structure and associated chemical reactivity of the Pd surface.
Der Sonnenblumen‐Trypsin‐Inhibitor 1 (SFTI‐1) in der Chemie und Biologie
Authors: de Veer Simon J. , White Andrew M. , Craik David J.
Published: July 2020

Natürlich vorkommende zyklische Peptide haben sich als wichtige Inspirationsquelle für die Weiterentwicklung des modernen pharmazeutischen Designs und der Synthesechemie erwiesen. Der Schwerpunkt dieses Aufsatzes liegt auf dem Sonnenblumen‐Trypsin‐Inhibitor 1 (SFTI‐1), einem der kleinsten in der Natur vorkommenden disulfidverbrückten zyklischen Peptide. SFTI‐1 hat einen ungewöhnlichen Biosyntheseweg, der mit einem Albuminvorläufer mit doppeltem Verwendungszweck beginnt und mit der Produktion eines Serinproteaseinhibitors mit hoher Affinität endet, der mit anderen viel größeren Inhibitoren konkurriert. Die Untersuchung der molekularen Grundlagen für die starre Struktur und anpassungsfähige Funktion von SFTI‐1 hat zu Denkanstößen geführt, die nun in verschiedenen Bereichen erste Resultate zeitigen. Hier untersuchen wir diese Anwendungen, um das wachsende Potenzial von SFTI‐1 als vielseitiges Templat für das Inhibitoren‐Engineering, als prototypisches Peptid zur Untersuchung von Inhibitormechanismen, als stabiles Gerüst für die Aufpfropfung bioaktiver Peptide und als Modellpeptid zur Bewertung peptidmimetischer Motive und Plattformtechnologien hervorzuheben.
Homologation of the Fischer Indolization: A Quinoline Synthesis via Homo‐Diaza‐Cope Rearrangement
Authors: Gerosa Gabriela Guillermina , Schwengers Sebastian Armin , Maji Rajat , De Chandra Kanta , List Benjamin
Published: July 2020

We disclose a new Brønsted acid promoted quinoline synthesis, proceeding via homo‐diaza‐Cope rearrangement of N‐aryl‐N′‐cyclopropyl hydrazines. Our strategy can be considered a homologation of Fischer's classical indole synthesis and delivers 6‐membered N‐heterocycles, including previously inaccessible pyridine derivatives. This approach can also be used as a pyridannulation methodology toward constructing polycyclic polyheteroaromatics. A computational analysis has been employed to probe plausible activation modes and to interrogate the role of the catalyst.
Sunflower Trypsin Inhibitor‐1 (SFTI‐1): Sowing Seeds in the Fields of Chemistry and Biology
Authors: de Veer Simon J. , White Andrew M. , Craik David J.
Published: July 2020

Nature‐derived cyclic peptides have proven to be a vast source of inspiration for advancing modern pharmaceutical design and synthetic chemistry. The focus of this Review is sunflower trypsin inhibitor‐1 (SFTI‐1), one of the smallest disulfide‐bridged cyclic peptides found in nature. SFTI‐1 has an unusual biosynthetic pathway that begins with a dual‐purpose albumin precursor and ends with the production of a high‐affinity serine protease inhibitor that rivals other inhibitors much larger in size. Investigations on the molecular basis for SFTI‐1′s rigid structure and adaptable function have planted seeds for thought that have now blossomed in several different fields. Here we survey these applications to highlight the growing potential of SFTI‐1 as a versatile template for engineering inhibitors, a prototypic peptide for studying inhibitory mechanisms, a stable scaffold for grafting bioactive peptides, and a model peptide for evaluating peptidomimetic motifs and platform technologies.
Ligational, density functional theory, and biological studies on some new Schiff base 2‐(2‐hydroxyphenylimine)benzoic acid (L) metal complexes
Authors: Elshwiniy Walaa H. , Ibrahim Asmaa G. , Sadeek Sadeek A. , Zordok Wael A.
Published: July 2020

The metal ions Co(II), Ni(II), Zn(II), Zr(IV), and Hg(II) reacted with synthesized Schiff base (L) in mole ratios 1:2 (M:L) formed metal complexes. The structure of the prepared compounds was identified based on the data obtained from elemental analyses, magnetic measurement, melting point, conductivity, Fourier‐transform infrared, UV–Vis., nuclear magnetic resonance spectroscopy, X‐ray diffraction (XRD) spectra, and thermal analysis (TG/DTG [thermogravimetric/differential thermal analysis]). The results indicate that the L bound as bidentate through the oxygen atom of the hydroxyl group and nitrogen atom of the azomethine group with the metal ions and the complexes is electrolyte in nature. TG/DTG studies confirmed the chemical formula for complexes. The kinetic and thermodynamic parameters such as E*, ΔH*, ΔS*, and ΔG* were determined by using Coats–Redfern and Horowitz–Metzger methods at n = 1 and n ≠ 1. The XRD patterns exhibited a semicrystalline nature lying between the amorphous and crystalline nature for L, (D), and (E), but the complexes (A), (B), and (C) possessed a crystalline character. Density functional theory confirmed the structural geometry of the complexes. In vitro antimicrobial activities were performed for L and its metal complexes.
Enhancement in Li+/Mg2+ separation from salt lake brine with PDA–PEI composite nanofiltration membrane
Authors: Ashraf Muhammad Awais , Wang Junfeng , Wu Baichun , Cui Penglei , Xu Baohua , Li Xingchun
Published: July 2020

Extraction of lithium from high Mg2+/Li+ ratio salt lake brine with the nanofiltration (NF) membrane is significantly challenging. Interfacial polymerization was utilized for the facile modification of NF membranes with polydopamine (PDA) and polyethylenimine (PEI) to enhance lithium separation efficiency. Comparing permeability and salts rejection (Li+ and Mg2+) of three NF membranes before and after PDA/PEI deposition, it was observed that separation efficiency was not only dependent on steric hindrance but also affected by Donnan exclusion mechanism. In the case of NF270 membrane after facile polymerization, due to small pore size distribution and low charge density confirmed by zeta potential measurements, Li+ permeability was reached about 95% at a flux of 21.33 L·m−2·h−1. Although with the DK membrane, separation factor SFLi/Mg was also increased up to 60 after modification, the pore narrowing effect significantly decreased lithium permeability and flux. Experimental results showed that facile modification not only enhanced stability and hydrophilicity but also reduced the high Mg2+/Li+ ratio from 30 to 4.1 in single‐stage separation.
A comprehensive study on Plantago ovata/PVA biocompatible nanofibers: Fabrication, characterization, and biological assessment
Authors: Allafchian Ali Reza , Kalani Sahar , Golkar Pooran , Mohammadi Hassan , Jalali Seyed Amir Hossein
Published: July 2020

In this study, a biocompatible nanofiber is fabricated using Plantago ovata mucilage (POM) combined with polyvinyl alcohol (PVA), which is considered as a non‐toxic polymer. High quality nanofibers were produced by controlling the electrospinning parameters after selecting an appropriate solvent for the POM/PVA combination (12% PVA and 3% POM). Electrospinning parameters, including high voltage, distance from collector to tip, feed rate and POM to PVA proportion were optimized following preparation of an aqueous POM/PVA solution. Using the results of scanning electron microscopy, the optimized electrospinning conditions for producing POM/PVA nanofibers were determined (high voltage = 18 kV, distance = 15 cm, feed rate = 0.125 ml/hr, PMM/PVA = 50/50) and uniform nanofibers with an average diameter of 250 nm were produced. The POM/PVA nanofiber sample was evaluated by determining the mechanical strength, characterization of produced nanofiber morphology, and investigating the cell viability by applying MTT assay. The bands for both POM and PVA from FTIR results showed that the samples remained stable. The tensile strength results showed that blending POM with PVA solution enhanced the Young's modulus by factor of 3.2 (0.2 MPa to 0.64 MPa). The MTT analysis on POM/PVA cell lines proved that the produced nanofiber considerably enabled the cellular proliferation. Enhancement in these analysis indicated how POM‐based nanofibers is a promising scaffold for cell culture, drug delivery systems and food additives.
Synergistic toughening and electrical functionalization of an epoxy usingMWCNTsand silane‐ /plasma‐activated basalt fibers
Authors: Quan Dong , Moloney Peter , Carolan Declan , Abourayana Hisham , Ralph Calvin , Ivankovic Alojz , Dowling Denis , Murphy Neal
Published: July 2020

This work studied the effects of adding short basalt fibers (BFs) and multi‐walled carbon nanotubes (MWCNTs), both separately and in combination, on the mechanical properties, fracture toughness, and electrical conductivity of an epoxy polymer. The surfaces of the short BFs were either treated using a silane coupling agent or further functionalized by atmospheric plasma to enhance the adhesion between the BFs and the epoxy. The results of a single fiber fragmentation test demonstrated a significantly improved BF/epoxy adhesion upon applying the plasma treatment to the BFs. This resulted in better mechanical properties and fracture toughness of the composites containing the plasma‐activated BFs. The improved BF/epoxy adhesion also affected the hybrid toughening performance of the BFs and MWCNTs. In particular, synergistic toughening effects were observed when the plasma‐activated BFs/MWCNTs hybrid modifiers were used, while only additive toughening effects occurred for the silane‐sized BFs/MWCNTs hybrid modifiers. This work demonstrated a potential to develop strong, tough, and electrically conductive epoxy composites by adding hybrid BF/MWCNT modifiers.
Autoantibodies to Malondialdehyde–Acetaldehyde Are Detected Prior to Rheumatoid Arthritis Diagnosis and After Other Disease Specific Autoantibodies
Authors: Mikuls Ted R. , Edison Jess , Meeshaw Elizabeth , Sayles Harlan , England Bryant R. , Duryee Michael J. , Hunter Carlos D. , Kelmenson Lindsay B. , Kay Moss Laura , Feser Marie L. , Wagner Brandie , Parish Mark C. , Deane Kevin D. , Thiele Geoffrey M.
Published: July 2020

Objective

To examine serum autoantibodies to malondialdehyde–acetaldehyde (MAA) prior to rheumatoid arthritis (RA) diagnosis.

Methods

Concentrations of anti‐MAA antibody isotypes, anti–cyclic citrullinated peptide 2 (anti–CCP‐2), and IgM rheumatoid factor (IgM‐RF) were evaluated before and after RA diagnosis in samples from cases (n = 214) and controls (n = 210). The timing of elevations in autoantibody concentrations relative to RA diagnosis was explored using separate mixed models for each antibody and/or isotype. Associations between prediagnosis autoantibody concentrations in RA patients were examined using mixed effects linear regression models.

Results

Concentrations of IgG (log2 difference 0.34) and IgA (log2 difference 0.43) anti‐MAA antibodies in RA patients diverged from controls at 3.0 years and 2.3 years prior to diagnosis, respectively (P < 0.05 for both). There was no evidence of case–control divergence for IgM anti‐MAA antibody concentration. Anti–CCP‐2 and IgM‐RF concentrations diverged between RA patients and controls beginning at 17.6 years and 7.2 years prior to RA diagnosis, respectively. All 3 anti‐MAA antibody isotypes (IgA, IgM, and IgG) were significantly associated with anti–CCP‐2 antibody and RF concentrations prior to diagnosis (β = 0.22–0.27 for IgM‐RF; β = 0.44–0.93 for anti–CCP‐2) (P < 0.001).

Conclusion

IgG and IgA anti‐MAA autoantibodies are elevated prior to RA diagnosis but appear later in the preclinical course than anti–CCP‐2 or RF. These findings suggest that MAA formation and anti‐MAA immune responses could play a role in the transition from subclinical autoimmunity to clinically apparent arthritis.
Immunodetection of urinary C‐terminal telopeptide fragment of type II collagen: An osteoarthritis biomarker analysis
Authors: Wang Shuwei , Su Shanlin , Yu Chunyun , Gopinath Subash C. B. , Yang Zhiquan
Published: July 2020

The urinary C‐terminal telopeptide fragment of type II collagen (uCTX‐II) has been reported as the efficient blood‐based biomarker for osteoarthritis, which affects knees, hands, spine, and hips. This study reports a sensing strategy with antibody‐conjugated gold nanoparticles (GNP) on an interdigitated electrode (IDE) to determine uCTX‐II. The GNP–antibody complex was chemically immobilized on the IDE surface through the amine linker. uCTX‐II was determined by monitoring the alteration in current upon interacting the GNP‐complexed antibody. This strategy was improved the detection by attracting higher uCTX‐II molecules, and the detection limit falls in the range of 10–100 pM with an acceptable regression value [y = 0.6254x − 0.4073, R² = 0.9787]. The sensitivity of the detection was recognized at 10 pM. Additionally, upon increasing the uCTX‐II concentration, the current changes were increased in a linear fashion. Control detection with nonimmune antibody and control protein do not increase the current level, confirming the specific detection of uCTX‐II. This method of detection helps in diagnosing osteoarthritis and its follow‐up treatment.
Cover Image, Volume 14, Issue 4
Authors: Brandt Kristin L. , Wooley Robert J. , Geleynse Scott C. , Gao Johnway , Zhu Junyong , Cavalieri Ralph P. , Wolcott Michael P.
Published: July 2020

The cover image is based on the Modeling and Analysis Article Impact of co‐product selection on techno‐economic analyses of alternative jet fuel produced with forest harvest residuals by Kristin Brandt et al., https://doi.org/10.1002/bbb.2111.

image
An efficient method for the determination of enantiomeric purity of racemic amino acids using micellar chromatography, a green approach
Authors: Alwera Shiv , Alwera Vijay , Sehlangia Suman
Published: July 2020

A simple, sensitive and green micellar liquid chromatographic method (RP‐HPLC) was developed for enantioseparation of four racemic amino acids, namely, (RS)‐selenomethionine, (RS)‐methionine, (RS)‐cysteine and (RS)‐penicillamine. An aqueous solution of sodium dodecyl sulfate and Brij‐35 was prepared and used as mobile phase for HPLC analysis. Activated esters of (S)‐ibuprofen, (S)‐ketoprofen and (S)‐levofloxacin were synthesized by reacting them with N‐hydroxybenzotriazole. These esters were characterized by UV, IR, 1HNMR, HRMS and elemental analysis. These chiral reagents (activated esters) were used for the synthesis of diastereomeric derivatives of the chosen amino acids. The diastereomeric derivatives were separated on a C18 column by micellar liquid chromatography. Chromatographic conditions were optimized by varying concentration of surfactant in aqueous solution, and by varying the concentration and pH of the buffer. The green assessment score was calculated for the developed method (78, an excellent green method score). In addition, density functional theory calculations were performed, using Gaussian 09 rev. A.02 and hybrid density functional B3LYP with a 6‐31G* basis set program, in order to develop lowest energy optimized structures of diastereomeric derivatives. The method was validated according to International Conference on Harmonization guidelines and the retention factor (k), selectivity factor (α), resolution factor (RS) and limit of detection (0.295 ng ml−1) and limit of quantification (0.896 ng ml−1) were calculated.
Transient effects of multi‐infusion ketamine augmentation on treatment‐resistant depressive symptoms in patients with treatment‐resistant bipolar depression – An open‐label three‐week pilot study
Authors: Zhuo Chuanjun , Ji Feng , Tian Hongjun , Wang Lina , Jia Feng , Jiang Deguo , Chen Ce , Zhou Chunhua , Lin Xiaodong , Zhu Jingjing
Published: July 2020

Introduction

While the psychiatric benefits of ketamine have been verified through clinical trials, there is limited information about ketamine augmentation in patients with treatment‐resistant bipolar depression (TRBPD). Hence, in the present study, we investigate the therapeutic efficacy and functional brain alterations associated with multi‐infusion ketamine augmentation in patients with TRBPD.

Methods

The present three‐week study included 38 patients with TRBPD, all of whom received a series of nine ketamine injections over the study period. The Hamilton Depression Rating Scale (HAMD) was used to assess the effects of multi‐infusion ketamine combined with mood stabilizers. Brain function was evaluated by global functional connectivity density (gFCD).

Results

Adjunctive treatment with multiple infusions of ketamine, when combined with a mood stabilizer, could effectively alleviate depressive symptoms for one week, yet the symptoms began to relapse during the second week. Functional brain alterations were detected via gFCD. Specifically, gFCD reductions were mainly found in the bilateral insula, right caudate nucleus, and bilateral inferior frontal gyrus, while increased gFCD was mainly located in the bilateral postcentral gyrus, subgenual anterior cingulate cortex, bilateral thalamus, and cerebellum. Although gFCD alterations were sustained for up to three weeks after the first ketamine infusion, the antidepressant effects of ketamine augmentation sharply declined from the end of the second week of treatment.

Conclusions

Multi‐infusion ketamine augmentation can rapidly alleviate depressive symptoms in patients with TRBPD. The clinical effects were primarily visible in the first week after treatment and partially sustained for two weeks; however, the therapeutic effects and related functional brain alterations sharply decreased from the end of the second week. Based on these findings, we demonstrated that the clinical efficacy and functional brain alterations induced by ketamine augmentation are transient.
The Ubiquitin Enigma: Progress in the Detection and Chemical Synthesis of Branched Ubiquitin Chains
Authors: Hua Xiao , Chu Guo‐Chao , Li Yi‐Ming
Published: July 2020

Ubiquitin chains with distinct topologies play essential roles in eukaryotic cells. Recently, it was discovered that multiple ubiquitin units can be ligated to more than one lysine residue in the same ubiquitin to form diverse branched ubiquitin chains. Although there is increasing evidence implicating these branched chains in a plethora of biological functions, few mechanistic details have been elucidated. This concept article introduces the function, detection and chemical synthesis of branched ubiquitin chains; and offers some future perspective for this exciting new field.
Spontaneous thrombosis of a transcatheter aortic valve replacement‐induced aortic root pseudoaneurysm
Authors: Costa Giulia , Ihlemann Nikolaj , Søndergaard Lars , De Backer Ole
Published: July 2020

Aortic annulus rupture or aortic root perforation is a rare complication of transcatheter aortic valve replacement (TAVR), requiring emergent cardiac surgery and carrying a high intraoperative mortality. Few cases can be managed conservatively, provided a strict clinical follow‐up. This study describes the case of a 78‐year‐old patient with a degenerated bicuspid aortic valve stenosis who presented with a late aortic root perforation following TAVR, which was successfully managed applying a “watchful waiting” approach. Cardiac computed tomography imaging played a pivotal role in the diagnosis and subsequent decision on treatment and clinical follow‐up.
Identification of Iron Carbides in Fe(−Na−S)/α‐Al2O3 Fischer‐Tropsch Synthesis Catalysts with X‐ray Powder Diffractometry and Mössbauer Absorption Spectroscopy
Authors: Paalanen Pasi P. , van Vreeswijk Sophie H. , Dugulan A. Iulian , Weckhuysen Bert M.
Published: July 2020

In Fe‐based Fischer‐Tropsch Synthesis (FTS), the Fe carbides form under the carburizing H2 : CO reaction atmosphere providing the active phases for hydrocarbon synthesis. H2 reduced Fe(−Na−S)/α‐Al2O3 catalyst materials, with and without Na−S promotion, were carburized under CO at 240–440 °C to form Fe carbides. X‐ray Powder Diffractometry (XRPD) with Rietveld Quantitative Phase Analysis (R‐QPA) and Mössbauer Absorption Spectroscopy (MAS) were used to identity and quantify the formed Fe carbide phases. The Fe carbides formed in order of increasing temperature are ϵ‐Fe3C, η‐Fe2C, χ‐Fe5C2 and θ‐Fe3C. θ‐Fe7C3 and a distorted χ‐Fe5C2 phase are formed at 25 bar CO (340 °C) from a Fe oxide precursor. Fe carbide formation was unaffected by Na−S addition, but it did increase Fe oxidation (≤290 °C) and preferred formation of χ‐Fe5C2 over θ‐Fe3C phase (≥390 °C). The results unify the often ambiguous Fe carbide identification and nomenclature and specify the role of Na−S in the carburization process.
Enantioselective synthesis of cyclic and linear diamines by imine cycloadditions
Authors: Chang Tsung‐Che , Pradipta Ambara R. , Tanaka Katsunori
Published: July 2020

Imine is one of the most versatile functional groups in chemistry and biochemistry fields. Although many biochemical reactions involve imine formation, the inherently unstable property of N‐alkyl‐α,β‐unsaturated imines still hindered their utilization in organic synthesis. In this article, we described that the N‐alkyl‐α,β‐unsaturated imines, which prepared from alkylamines and acrolein, could smoothly react through [4 + 4] cycloaddition to give eight‐membered diazacyclooctane derivatives in excellent yields. Under a similar condition, in the presence of formaldehyde, the [4 + 2] and [4 + 2 + 2] cycloadditions could lead to the formation of six‐membered hexahydropyrimidine or eight‐membered triazacyclooctanes, depending on the substituent of aldehydes. Moreover, an easy functional group manipulation of the cyclic products obtained from these cycloadditions can provide variously substituted chiral linear diamines. We can utilize these novel reactivities to reveal the unknown and essential properties of many biological processes that involve N‐alkyl‐unsaturated imines.
Construction of a Nano‐rectangular Zn(II)‐Yb(III) Complex with Near‐Infrared Luminescent Response towards Metal Ions
Authors: Liu Xia , Yang Xiaoping , Ma Yanan , Liu Jieni , Shi Dongliang , Niu Mengyu
Published: July 2020

Summary of main observation and conclusion

One six‐metal Zn(II)‐Yb(III) complex [Zn2Yb4L2(OAc)10(OH)2(CH3OH)2] (1) was constructed from Schiff base ligand bis(3‐methoxysalicylidene)ethylene‐1,2‐phenylenediamine (H2L). 1 shows a nanoscale rectangular structure with dimensions of approximately 0.8 nm × 1.1 nm × 2.8 nm. Excited by ligand‐centered absorption bands, 1 shows typical near‐infrared emission of Yb3+ ion. Interestingly, 1 exhibits lanthanide luminescent response towards metal ions, especially to Cd2+ at ppm level.
Comparing Onset of Biosimilar Versus Generic Competition in the United States
Authors: Beall Reed F. , Ronksley Paul E. , Wick James , Darrow Jonathan J. , Sarpatwari Ameet , Kesselheim Aaron S.
Published: July 2020

We sought to compare expected and observed biosimilar and generic entry dates among new drugs approved by the US Food and Drug Administration (FDA) between 2000 and 2012. We defined expected biosimilar and generic entry dates as the later of the expiration of the key patent term or statutory exclusivity (12 years for biologics, 5 years for small molecule drugs not indicated for a rare disease, and 7 years for small molecule drugs indicated for a rare disease; plus 6 months if a pediatric extension had been granted). For drugs with expected entry prior to 2019, we calculated the proportion with observed biosimilar or generic entry. The expected biosimilar entry dates were estimated to be a median of 12.3 years (interquartile range (IQR) 12.0–14.0, n = 60) after FDA approval. The 12‐year biologic statutory exclusivity period comprised 98% of the median expected protection period. By contrast, expected generic entry was estimated to be a median of 12.2 years (IQR 8.4–14.0, n=268), or 7.2 years after the 5‐year small molecule statutory exclusivity (59% of the total expected market protection period). By 2019, observed biosimilar entry occurred in 12% of cases (3/25) and observed generic entry in 65% (101/155). We concluded that expected US market exclusivity periods are similar for biologic and small molecule drugs. Statutory exclusivity plays a more substantial role in market exclusivity protection for biologics. Biosimilar competition, currently lagging behind generic competition, will likely increase as the biosimilar market becomes established.
Unsymmetrical 2,4,6‐Triarylpyridines as Versatile Scaffolds for Deep‐Blue and Dual‐Emission Fluorophores
Authors: Fontes Luís F. B. , Nunes da Silva Raquel , Silva Artur M. S. , Guieu Samuel
Published: July 2020

Pyridines substituted with different aromatic groups at C‐2, C‐4 and C‐6 were prepared following a Kröhnke synthetic route. Introducing ortho‐anisole at C‐2 resulted in deep blue emitters in solution, with quantum yields up to 74 %. On the other hand, when ortho‐phenol was introduced, forming a strong hydrogen bond with the pyridine nitrogen, excited‐state intramolecular proton transfer was witnessed by the dual emission of the fluorophores, which is sensitive to the dye environment. The phenyl ring at C‐4 was used to introduce electron‐donating or withdrawing groups, to fine‐tune the photophysical properties of the dyes. Crystal structures of the fluorophores, together with theoretical studies using DFT/TD‐DFT calculations, were used to rationalize the experimental photophysical properties of the two families of dyes. Unsymmetrical 2,4,6‐triarylpyridines are therefore versatile scaffolds for the preparation of deep‐blue and dual emission fluorophores, and are promising building blocks for luminescent devices and sensors.
Emperipolesis of lymphocytes by mesothelial cells in pleural effusion involved by T‐lymphoblastic lymphoma
Authors: AbdullGaffar Badr
Published: July 2020

Emperipolesis is a physiologic or pathologic phenomenon characterized by the presence of intact viable cells within the cytoplasm of another cell. It has been described in normal tissues and in a variety of inflammatory and neoplastic lesions such as Rosai‐Dorfman disease, tumors, hematopoietic disorders and rarely lymphomas. Emperipolesis by mesothelial cells is rare. Few cases of mesothelial emperipolesis of neoplastic lymphocytes in pleural effusions involved by lymphomas have been reported in the literature. Its etiopathogenesis and significance are controversial and speculative. We report a case of a 36‐year‐old man who presented with cough, chest pain, breathing difficulty, pericardial, and bilateral pleural effusions secondary to mediastinal T‐lymphoblastic lymphoma. Pleural fluid cytology slides and cell block sections showed numerous single dispersed neoplastic lymphoblasts with occasional giant multinucleated mesothelial cells with emperipolesis of lymphocytes. The background showed scattered and clumped apoptotic karyorrhexis debris and reactive mesothelial cells. Cell block immunohistochemistry showed CD3, CD5, CD7, CD10, CD99, and TdT positive lymphocytes, consistent with involvement by T‐lymphoblastic lymphoma. The giant cells were positive for cytokeratin, calretinin and WT1 confirming their mesothelial origin. Lymphoid effusions with emperipolesis may raise a potential diagnostic pitfall because they may morphologically be confused with other inflammatory and neoplastic lesions. This cell‐in‐cell phenomenon can be a helpful clue in the differential diagnosis of lymphocyte‐rich effusions since it has been described in association with lymphomas. It might shed some light on the lymphocyte‐mesothelial interaction and the potential phagocytic antigen‐presenting properties of mesothelial cells under certain circumstances.
The pursuit of understanding multinucleated giant cells in indeterminate and malignant thyroid cytology samples
Authors: Aykutlu Umut , Aydın Ozkan , Gundogdu Betul
Published: July 2020

BACKGROUND

Multinucleated giant cell (MGC) present in a variety of non‐neoplastic and neoplastic lesions of the thyroid on cytology samples. We aimed to investigate whether certain MGC features that can help us in routine cytopathology practice.

METHOD

One hundred and thirty seven cases thyroid fine‐needle aspiration material, which was diagnosed as indeterminate or malignant according to the Bethesda categorization, were reviewed. All cytomorphological features of the MGCs were documented. These features correlated with Bethesda categories and the final diagnosis of the subsequent surgical specimen.

RESULTS

The presence of the MGCs was identified in 42% of the samples (58 cases‐total 236 MGCs). Eighty eight of them (37%) had dense cytoplasm, 148 of them had foamy cytoplasm. The mean number of dense and foamy MGC per case was higher in the malignant category (3.2 for dense MGC and 6 for foamy MGC per case). All dense MGCs were found to be in patients with papillary thyroid carcinoma (PTC). Remarkably, follicular patterned lesions had less often dense MGC compared to papillary patterned lesions (16.6% and 46.8% respectively). We detected a nuclear irregularity in 49 dense MGC (55%), groove‐like features in 24 dense MGC (27.2%), and presence of some material/cell in 8 dense MGC (9%).

CONCLUSION

The presence of dense MGC is an important finding for guiding accurate Bethesda categorization, especially in indeterminate and malignant categories. Besides, the presence of some material or cell in MGCs cytoplasm can be an important indicator for the prognosis of the PTC cases.
The complexities associated with new psychoactive substances in influent wastewater: The case of 4‐ethylmethcathinone
Authors: Bade Richard , Abbate Vincenzo , Abdelaziz Ahmed , Nguyen Lynn , Trobbiani Stephen , Stockham Peter , Elliott Simon , White Jason M. , Gerber Cobus
Published: July 2020

Consumption of new psychoactive substances (NPS) is an international problem for health, policing, forensic, and analytical laboratories. The transience of these substances in the community, combined with continual slight structural changes to evade legislation makes the elucidation of NPS an analytical challenge. This is amplified in a matrix as complex as wastewater. For that reason, suspect and non‐target methodologies, employing high resolution mass spectrometry are the most appropriate current tool to facilitate the identification of new and existing compounds. In the current work, a qualitative screening method of influent wastewater using liquid chromatography‐high resolution mass spectrometry showed a strong signal at m/z 192.1382 – identical to that of two NPS standards that were in our method (pentedrone and 4‐methylethcathinone), and with identical fragment ions, but the retention times did not match. This work shows the methodology followed to identify this compound, highlighting the challenges of the identifying “new” compounds in influent wastewater.
Tentative identification of the phase I and II metabolites of two synthetic cathinones, MDPHP and α‐PBP, in human urine
Authors: Kavanagh Pierce , Gofenberg Mariia , Shevyrin Vadim , Dvorskaya Oksana , Dowling Geraldine , Grigoryev Andrej
Published: July 2020

Cathinone derivatives are one of the more prominent groups of new psychoactive substances in terms of the number of forensic case reports and the variety of chemical structures available. These substances often sold as “bath salts” are classified as psychostimulants. Using liquid chromatography‐high resolution mass spectrometry, the metabolites of two pyrrolidine cathinone derivatives, α‐PBP and the less common MDPHP, were tentatively identified in urine samples collected from patients admitted to hospital following drug intoxications. The major metabolic pathways for α‐PBP and MDPHP were similar to those of their more common analogs (α‐PVP and MDPV). Metabolites arising from hydroxylation, reduction of the carbonyl group to an alcohol, oxidation to form a lactam and subsequent ring‐opening, and a combination of these processes were identified. In addition, biotransformations of the benzodioxole moiety in MDPHP included demethylenation with subsequent methylation and carboxylation of the butyl group. The majority of the hydroxylated metabolites of α‐PBP and MDPHP were found to be glucuronidated. Both α‐PBP and MDPHP undergo extensive metabolism and the chromatographic peak areas of the metabolites were found to be comparable to or exceeded those of the parent substances. Metabolites resulting from demethylenation and subsequent methylation (MDPHP), reduction of carbonyl group (α‐PBP), and oxidation to form a lactam combined with ring‐opening (α‐PBP and MDPHP) were found to be the most useful target analytes for the confirmation of ingestion.
Don't shortchange a long illness: A commentary on Severe and Enduring Anorexia Nervosa
Authors: Attia Evelyn
Published: July 2020

Wonderlich et al.'s manuscript “Severe and Enduring Anorexia Nervosa: Update and Observations about the Current Clinical Reality” reviews Severe and Enduring Anorexia Nervosa (SE‐AN) from several perspectives, hoping to stimulate discussion among clinicians, researchers, and other stakeholders about needed next steps for furthering the science relevant to the severe and enduring form of illness that affects a subgroup of individuals with AN. Among the important reasons for a new discussion of SE‐AN is that health care has evolved in ways that have reduced comprehensive services for those who are more seriously affected. It is critical that adults with SE‐AN be examined empirically to help identify effective strategies for clinical management and that health care policies assure parity for this seriously affected group.
Examining vegetarianism, weight motivations, and eating disorder psychopathology among college students
Authors: Zickgraf Hana F. , Hazzard Vivienne M. , O'Connor Shannon M. , Simone Melissa , Williams‐Kerver Gail A. , Anderson Lisa M. , Lipson Sarah K.
Published: July 2020

Objective

Previous research has suggested a link between vegetarianism, broadly defined, and symptoms of eating disorders (ED). However, the literature supporting this link is mixed and limited by possible measurement artifacts. Using data from a national sample of college students, the present study examines ED symptomatology among three groups: (a) vegetarians whose meat avoidance is motivated by weight concerns; (b) non‐weight motivated vegetarians; and (c) nonvegetarians.

Method

Participants include 9,910 students from 12 colleges and universities across the United States who participated in the web‐based Healthy Bodies Study. ED symptomatology was measured using the Short‐Eating Disorder Examination‐Questionnaire (S‐EDE‐Q). First, multi‐group confirmatory factor analysis was conducted to test measurement invariance (MI) of the S‐EDE‐Q across weight‐motivated vegetarians, non‐weight‐motivated vegetarians, and nonvegetarians. Gender‐ and BMI‐adjusted ANCOVA was used to compare S‐EDE‐Q scores across groups.

Results

9.3% of participants were vegetarian. Cis‐women and gender minority students were more likely to be vegetarian; those who became vegetarians after entering college were more likely to report weight‐related motivations. Strict MI was supported for the S‐EDE‐Q global and subscale scores. Weight‐motivated vegetarians reported higher levels of restraint, shape/weight overvaluation, body dissatisfaction, and global ED psychopathology relative to other participants.

Discussion

To our knowledge, this is the first to explicitly link weight motivations for vegetarianism to ED psychopathology in a large, representative sample of young adults. Results suggest that students presenting with ED symptoms should be assessed for their motivations for adopting a vegetarian diet, and this information should be considered in treatment decisions.
Volatile organic compounds from leaf litter decomposition alter soil microbial communities and carbon dynamics
Authors: McBride Steven G. , Choudoir Mallory , Fierer Noah , Strickland Michael S.
Published: July 2020

Investigations into the transfer of carbon from plant litter to underlying soil horizons have primarily focused on the leaching of soluble carbon from litter belowground or the mixing of litter directly into soil. However, previous work has largely ignored the role of volatile organic compounds (VOCs) released during litter decomposition. Unlike most leaf carbon, these litter‐derived VOCs are able to diffuse directly into the soil matrix. Here, we used a 99‐d microcosm experiment to track VOCs produced during microbial decomposition of 13C‐labeled leaf litter into soil carbon fractions where the decomposing litters were only sharing headspace with the soil samples, thus preventing direct contact and aqueous movement of litter carbon. We also determined the effects of these litter‐derived VOCs on soil microbial community structure. We demonstrated that the litter VOCs contributed to all measured soil carbon pools. Specifically, VOC‐derived carbon accounted for 2.0, 0.61, 0.18, and 0.08% of carbon in the microbial biomass, dissolved organic matter, mineral‐associated organic matter, and particulate organic matter pools, respectively. We also show that litter‐derived VOCs can affect soil bacterial and fungal community diversity and composition. These findings highlight the importance of an underappreciated pathway where VOCs alter soil microbial communities and carbon dynamics.
A Lightweight, Adhesive, Dual‐Functionalized Over‐Coating Interphase Toward Ultra‐Stable High‐Current Density Lithium Metal Anodes
Authors: Li Shaowen , Ma Yue , Wei Bingqing
Published: July 2020

Coherent manipulation of the lithium plating pattern is at the heart of the safe operation of metallic anodes in the battery technologies. In this article, a lightweight (~0.3 mg cm−2), dual‐functionalized carbon spheres are anchored onto the Cu foil as the interfacial protective layer via the chelation process of the catechol groups in the polydopamine precursor and the copper foil. The dual‐functionalized carbon spheres exhibit the intriguing complementary features: Lithiophilic nitrogen dopants favor the Li+ ion absorption and mitigate the nucleation barrier, while the micro/mesopore reservoir spatially homogenizes the ion flux distribution, confining the metallic propagation without dendrite‐like protrusions. The metallic anode exhibits an ultra‐stable plating/stripping process for 1400 hr with the average Coulombic efficiency of ~99%. A full‐cell prototype is constructed by pairing the N‐doped carbon spheres on the bare Cu (NCS‐Cu) electrode with the high‐mass‐loading LiVPO4F (12.5 mg cm−2) cathode that can deliver a high energy density of 421.2 Wh kg−1 with the highest power density of 2106 W kg−1 to promise the anode use for high‐power/energy‐dense metallic batteries.
Association of iron deficiency, anaemia, and functional outcomes in patients undergoing edge‐to‐edge mitral valve repair
Authors: Iliadis Christos , Metze Clemens , Körber Maria Isabel , Baldus Stephan , Pfister Roman
Published: July 2020

Aims

Patients undergoing percutaneous mitral valve repair (PMVR) show a substantial heterogeneity of prognostic and symptomatic benefit. Iron deficiency and anaemia are associated with worse outcomes in heart failure patients. We investigated the impact of these comorbidities on functional and clinical outcome after PMVR.

Methods and results

Iron deficiency and anaemia were prospectively assessed in 130 patients undergoing PMVR with MitraClip. Associations with functional outcomes at 6 weeks [6 min walking distance (6MWD), Short‐Form‐36 physical component score, and Minnesota Living with Heart Failure Questionnaire score, New York Heart Association class] and long‐term clinical outcome were examined. Iron deficiency and anaemia were frequent with 52% and 50%, respectively. Patients with anaemia showed significant worse baseline functional measures, whereas patients with iron deficiency showed only a trend for lower baseline 6MWD. The benefit in functional outcomes after PMVR was notable and did not differ significantly by iron deficiency or anaemia status (range of median changes in 6MWD 35 to 45 m, physical component score 5.6 to 7.2, Minnesota Living with Heart Failure Questionnaire −8.0 to −10.5; improvement of ≥1 New York Heart Association class 69% to 80%). Anaemia was associated with higher risk for the combined endpoint of mortality and heart failure hospitalization (hazard ratio: 2.51; 95% confidence interval: 1.24–5.1; P = 0.01), whereas iron deficiency showed a trend towards more heart failure hospitalizations (hazard ratio: 2.94; 95% confidence interval: 0.94–9.03; P = 0.09).

Conclusions

The prevalence of iron deficiency and anaemia is high in patients undergoing MitraClip. Clinical baseline status and long‐term outcome were worse particularly in patients with anaemia. However, the functional benefit of PMVR was equal in patients with and without iron deficiency and anaemia.
Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio‐Oncology Council of the European Society of Cardiology (ESC)
Authors: Čelutkienė Jelena , Pudil Radek , López‐Fernández Teresa , Grapsa Julia , Nihoyannopoulos Petros , Bergler‐Klein Jutta , Cohen‐Solal Alain , Farmakis Dimitrios , Tocchetti Carlo Gabriele , von Haehling Stephan , Barberis Vassilis , Flachskampf Frank A. , Čeponienė Indrė , Haegler‐Laube Eva , Suter Thomas , Lapinskas Tomas , Prasad Sanjay , de Boer Rudolf A. , Wechalekar Kshama , Anker Markus S. , Iakobishvili Zaza , Bucciarelli‐Ducci Chiara , Schulz‐Menger Jeanette , Cosyns Bernard , Gaemperli Oliver , Belenkov Yury , Hulot Jean‐Sébastien , Galderisi Maurizio , Lancellotti Patrizio , Bax Jeroen , Marwick Thomas H. , Chioncel Ovidiu , Jaarsma Tiny , Mullens Wilfried , Piepoli Massimo , Thum Thomas , Heymans Stephane , Mueller Christian , Moura Brenda , Ruschitzka Frank , Zamorano Jose Luis , Rosano Giuseppe , Coats Andrew J.S. , Asteggiano Riccardo , Seferovic Petar , Edvardsen Thor , Lyon Alexander R.
Published: July 2020

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio‐Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio‐Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio‐oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three‐dimensional ejection fraction, are proposed. The protocol for baseline pre‐treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2‐targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr‐Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio‐oncology are discussed.
Ammonia Synthesis via Electrochemical Nitrogen Reduction Reaction on Iron Molybdate under Ambient Conditions
Authors: Chen Cong , Liu Yang , Yao Yuan
Published: July 2020

The electrochemical nitrogen reduction reaction (NRR) is an environmentally friendly and sustainable strategy for ammonia synthesis under ambient conditions, in comparison with the traditional Haber‐Bosch process. However, the N≡N triple bond has a high bond energy, which causes the electrochemical NRR to suffer from sluggish kinetics. Inevitable ammonia contamination also disturbs the quantification of ammonia produced from the electrochemical NRR. To construct a bimetal‐atom active center to mimic nitrogenase in nature, we herein prepared iron molybdate, Fe2(MoO4)3, using it as catalyst for electrochemical NRR. It is active and stable with an NH3 yield rate of ca. 7.5 µg h–1 mgcat–1 and a Faradaic efficiency of ca. 1.0 % in 0.1 m Na2SO4 at –0.7 V for 2 h, due to synergistic effect of bimetal atoms. A series of comparative experiments were subsequently conducted to reveal the origin of the activity and estimate the deviation due to ammonia contamination from the environment. Our results hold great promise for both the design of catalysts and the accurate quantification of catalytic activity for electrochemical NRR.