bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults
Authors: Martinez‐Majander Nicolas , Artto Ville , Ylikotila Pauli , von Sarnowski Bettina , Waje‐Andreassen Ulrike , Yesilot Nilufer , Zedde Marialuisa , Huhtakangas Juha , Numminen Heikki , Jäkälä Pekka , Fonseca Ana C. , Redfors Petra , Wermer Marieke J. H. , Pezzini Alessandro , Putaala Jukka ,   the SECRETO Study Group
Published: October 2020

Objective

To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO).

Methods

We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age‐ and sex‐matched (±5 years) stroke‐free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist‐to‐hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen.

Results

The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63–3.76) and MA (OR = 3.50, 95% CI = 2.19–5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61–5.47; OR = 4.32 for MA, 95% CI = 2.16–8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32–4.61; OR = 3.61 for MA, 95% CI = 1.75–7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right‐to‐left shunt in patients with PFO.

Interpretation

MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242–253
A General Strategy to Design Highly Fluorogenic Far‐Red and Near‐Infrared Tetrazine Bioorthogonal Probes
Authors: Mao Wuyu , Tang Jie , Dai Liqun , He Xinyu , Li Jie , Cai Larry , Liao Ping , Jiang Ruotian , Zhou Jingwei , Wu Haoxing
Published: October 2020

Highly fluorogenic tetrazine bioorthogonal probes emitting at near‐infrared wavelengths are in strong demand for biomedical imaging applications. Herein, we have developed a strategy for forming a palette of novel Huaxi‐Fluor probes in situ, whose fluorescence increases hundreds of times upon forming the bioorthogonal reaction product, pyridazine. The resulting probes show large Stokes shifts and high quantum yields. Manipulating the conjugate length and pull–push strength in the fluorophore skeleton allows the emission wavelength to be fine‐tuned from 556 to 728 nm. The highly photo‐stable and biocompatible probes are suitable for visualizing organelles in live cells without a washing step and for imaging of tumors in live small animals to depths of 500 μm by two‐photon excitation.
Assembly of Complex 1,4‐Cycloheptadienes by (4+3) Cycloaddition of Rhodium(II) and Gold(I) Non‐Acceptor Carbenes
Authors: Armengol‐Relats Helena , Mato Mauro , Echavarren Antonio M.
Published: October 2020

The formal (4+3) cycloaddition of 1,3‐dienes with Rh(II) and Au(I) non‐acceptor vinyl carbenes, generated from vinylcycloheptatrienes or alkoxyenynes, respectively, leads to 1,4‐cycloheptadienes featuring complex and diverse substitution patterns, including natural dyctiopterene C′ and a hydroxylated derivative of carota‐1,4‐diene. A complete mechanistic picture is presented, in which Au(I) and Rh(II) non‐acceptor vinyl carbenes were shown to undergo a vinylcyclopropanation/Cope rearrangement or a direct (4+3) cycloaddition that takes place in a non‐concerted manner.
Isomerisierungsreaktionen in anionischen mesoionischen Carbenboraten und Kontrolle der Eigenschaften und Reaktivität in den entstehenden CoII‐Komplexen durch agostische Wechselwirkungen
Authors: Stubbe Jessica , Neuman Nicolás I. , McLellan Ross , Sommer Michael G. , Nößler Maite , Beerhues Julia , Mulvey Robert E. , Sarkar Biprajit
Published: October 2020

Wir präsentieren anionische Borat‐basierte bi‐mesoionische Carbenverbindungen vom Typ 1,2,3‐Triazol‐4‐yliden, die C‐N‐Isomerisierungen eingehen können. Die isomerisierten Verbindungen sind ausgezeichnete Liganden für CoII‐Zentren. Starke agostische Wechselwirkungen, ausgehend von den “C‐H”‐Gruppen der Cyclohexylsubstituenten, führen zu einem unüblichen quadratisch‐planaren CoII‐Komplex im Low‐Spin‐Zustand, der gegenüber externen Substraten keine Reaktivität zeigt. Solche agostischen Wechselwirkungen sind nicht im Komplex mit Phenylsubstituenten am Boratrückgrat zu finden. Dieser Komplex zeigt ein tetraedrisches High‐Spin‐CoII‐Zentrum, das gegenüber externen Substraten, einschließlich Disauerstoff, reaktiv ist. Unseres Wissens ist dies die erste Untersuchung agostischer Wechselwirkungen durch Einkristall‐EPR‐Spektroskopie. Wir können zeigen, dass die Struktur und Eigenschaften dieser CoII‐Komplexe durch Wechselwirkungen innerhalb der sekundären Koordinationssphäre stark beeinflusst werden. Zusätzlich konnten wir eine spezifische Ligandenumlagerung für die Klasse der mesoionischen Carbene aufdecken.
Carbenaporphyrine: eine Lücke in der Chemie N‐heterocyclischer Carbene schließt sich
Authors: Maulbetsch Theo , Kunz Doris
Published: October 2020

Die Synthese eines NHC‐haltigen porphyrinoiden Liganden wird vorgestellt. Das formal antiaromatische makrocyclische 20‐πe−‐Ligandgerüst kann über eine 1,3‐dipolare Cycloaddition (“Klick”‐Reaktion) aufgebaut werden, in der zwei Triazoleinheiten gebildet und nachfolgend zum entsprechenden Triazoliummakrocyclus alkyliert werden. Die Deprotonierung der Ligandvorstufe mit Lithiumbasen zum entsprechenden Dilithiumcarbenaporphyrin‐Komplex und dessen Transmetallierung auf Scandium führen zu Komplexen, die orange Fluoreszenz zeigen. Optische Untersuchungen in Kombination mit TD‐DFT‐Studien bestätigen einen eigenen aromatischen Charakter für jede heterocyclische Einheit anstelle eines konjugierten antiaromatischen Makrocyclus sowohl im Ligandvorläufer als auch in den Metallkomplexen. Während die geometrischen Merkmale des Carbenaporphyrin‐Liganden denen des Porphyrins stark ähneln, zeigen DFT‐Berechnungen eine stärkere Elektronendonorfähigkeit des neuen Liganden.
Site‐Selective Electrochemical Benzylic C−H Amination
Authors: Hou Zhong‐Wei , Liu Ding‐Jin , Xiong Peng , Lai Xiao‐Li , Song Jinshuai , Xu Hai‐Chao
Published: October 2020

C−H/N‐H cross‐coupling is an ideal strategy to synthesize various amines but remains challenging owing to the requirement for sacrificial chemical oxidants and the difficulty in controlling the regio‐ and chemo‐selectivity. Herein we report a site‐selective electrochemical amination reaction that can convert benzylic C−H bonds into C‐N linkages via H2 evolution without need for external oxidants or metal catalysts. The synthetic strategy involves anodic cleavage of benzylic C−H to form a carbocation intermediate, which is then trapped with an amine nucleophile leading to C−N bond formation. Key to the success is to include HFIP as a co‐solvent to modulate the oxidation potentials of the alkylbenzene substrate and the aminated product to avoid overoxidation of the latter.
Investigation of mononuclear, dinuclear, and trinuclear transition metal (II) complexes derived from an asymmetric Salamo‐based ligand possessing three different coordination modes
Authors: Bian Ruo‐Nan , Wang Ji‐Fa , Xu Xin , Dong Xiu‐Yan , Ding Yu‐Jie
Published: October 2020

A new asymmetric Salamo‐based ligand H2L was synthesized using 3‐tert‐butyl‐salicylaldehyde and 6‐methoxy‐2‐[O‐(1‐ethyloxyamide)]‐oxime‐1‐phenol. By adjusting the ratio of the ligand H2L and Cu (II), Co (II), and Ni (II) ions, mononuclear, dinuclear, and trinuclear transition metal (II) complexes, [Cu(L)], [{Co(L)}2], and [{Ni(L)(CH3COO)(CH3CH2OH)}2Ni] with the ligand H2L possessing completely different coordination modes were obtained, respectively. The optical spectra of ligand H2L and its Cu (II), Co (II) and Ni (II) complexes were investigated. The Cu (II) complex is a mononuclear structure, and the Cu (II) atom is tetracoordinated to form a planar quadrilateral structure. The Co (II) complex is dinuclear, and the two Co (II) atoms are pentacoordinated and have coordination geometries of distorted triangular bipyramid. The Ni (II) complex is a trinuclear structure, and the terminal and central Ni (II) atoms are all hexacoordinated, forming distorted octahedral geometries. Furthermore, optical properties including UV–Vis, IR, and fluorescence of the Cu (II), Co (II), and Ni (II) complexes were investigated. Finally, the antibacterial activities of the Cu (II), Co (II), and Ni (II) complexes were explored. According to the experimental results, the inhibitory effect was found to be enhanced with increasing concentrations of the Cu (II), Co (II), and Ni (II) complexes.
New polyester biodegradable scaffolds for chondrocyte culturing: Preparation, properties, and biological activity
Authors: Gadomska‐Gajadhur Agnieszka , Kruk Aleksandra , Dulnik Judyta , Chwojnowski Andrzej
Published: October 2020

An innovative modification of the wet inversion phase method, consisting in the use of a polymer nano‐nonwoven as a nonclassic pore precursor. Mechanical properties of the obtained scaffolds were determined, their hydrophilic properties (serum absorbability) were tested, and the content of residues of materials used in the scaffold preparation was determined. Nontoxicity of the developed scaffolds toward T lymphocyte cells was proved. Cultures of primary chondrocytes were obtained successfully. It was proved that an addition of a polymer nano‐nonwoven changes the properties of the scaffolds favorably in respect of their subsequent application in tissue engineering.
Molecular dynamics simulation on the adhesion mechanism at polymer‐mold interface of microinjection molding
Authors: Yang Jin , Zhai Zhanyu , Liu Jiezhen , Weng Can
Published: October 2020

In the demolding process of microinjection molding, the defects of microstructures are often caused by the strong adhesion between polymer and mold. In order to study the adhesion mechanism, the molecular dynamics (MD) method was proposed to simulate the adsorption of cycloolefin copolymer (COC) molecules on mold surfaces. The evolution snapshots of COC molecular chains of three interfacial models were obtained to directly demonstrate the adhesive strength of interfaces. Meanwhile, the work of adhesion, the relative concentration, the potential energy, and the radial distribution function (RDF) were calculated to explain the interaction mechanism of polymer‐mold interfaces. The simulation results showed that the COC‐Ni interface had the largest work of adhesion and the lowest potential energy, compared with other two interfaces. The van der Waals (VDW) energy, which mainly derived from the interaction between H atoms in COC and the mold material was the only nonbond interaction energy at the COC‐Ni and COC‐Si interfaces, while the electrostatic energy existed in COC‐Al2O3 interface. In order to reduce the adhesion between polymer and mold, fluorine (F) element could be doped into the Ni mold.
Spawning habitat suitability for coastal cutthroat trout: Microhabitat and mesohabitat
Authors: Boessow Steven N. , Beecher Hal A. , Gates Kiza K.
Published: October 2020

The conservation of aquatic species with complex life histories requires the protection of habitat for each life stage. Coastal cutthroat trout (Oncorhynchus clarkii clarkii) exhibit both mobile and sessile stages and are of conservation concern in north‐western North America. Models that predict how habitat changes with flow can inform water management for the species but rely on habitat descriptors that change with flow and are not suited to sessile life stages.

Spawning and incubation habitat availability and use for coastal cutthroat trout were assessed in mesohabitats and microhabitats. Primary channel units were tallied, dimensions were measured, redds were counted, and redd locations within channel units were measured.

Primary channel units were subdivided based on relative residual depth (RRD, bed elevation in relation to maximum pool depth) and hydraulic control (HC, the lowest point on the highest ridge across the riffle that controls the water surface elevation in the upstream pool). Habitat suitability was calculated for depth (D), velocity (V), Froude number (Fr), substrate (S), RRD, and channel units.

Redds in riffles and pools were close to hydraulic controls; suitability decreased upstream in pools and downstream in riffles. Maximum suitability values were: 21–24 cm for D, 0.05–0.10 for RRD, 61–64 cm s−1 for V, >0.80 for Fr, and 1.3 to <3.8 cm for S. Channel units, RRDs, and microhabitat better identified spawning habitat than microhabitat alone.

The results suggest that RRD and stage of zero flow are good indicators of habitat suitability for spawning through fry emergence and could be adapted for use with other species. This work generates criteria for delineating flow‐independent channel units that can be used to set more protective instream flows, prioritize the acquisition of instream water or conservation easements to protect critical habitat, and inform restoration projects to optimize habitat availability.
Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives
Authors: Shi Jiuzhou , Lu Wen , Chen Jichao , Sun Lu , Yang Shilong , Zhou Mengyi , Xu Li , Ma Ying , Yu Long
Published: October 2020

Ten coumarin‐3‐formamido derivatives,N‐benzyl‐coumarin‐3‐carboxamide (2),N‐fluorobenzyl‐coumarin‐3‐carboxamide (3–5),N‐methoxybenzyl‐coumarin‐3‐carboxamide (6–8),N‐((1‐methyl‐1H‐imidazol‐5‐yl)methyl)‐coumarin‐3‐carboxamide (9),N‐(thiophen‐2‐ylmethyl)‐coumarin‐3‐carboxamide (10), andN‐(furan‐2‐ylmethyl)‐coumarin‐3‐carboxamide (11), were synthesized and characterized. Compound5crystallizes in a monoclinic system P21/c space group with four chemical formulas in a unit cell; molecules of compound5are self‐assembled into a two‐dimensional supramolecular structure by intermolecular hydrogen bonds and C⋯C π stacking. The potential anticancer effects of these compounds on HeLa (cervical carcinoma), MCF‐7 (breast), A549 (lung), HepG2 (liver), and human umbilical vein (HUVEC) cells were examined. Compared with compounds1–8and10–11, compound9exhibits potent in vitro cytotoxicity against HeLa cells and lower cytotoxicity against normal cells. Therefore, further in‐depth investigations of compound9were performed. Absorption titration experiments and fluorescence spectroscopy studies suggested that compound9binds to DNA through the intercalation mode.
Finite‐time stability analysis of a class of discrete‐time switched nonlinear systems with partial finite‐time unstable modes
Authors: Gao Zairui , Wang Ziyun , Wu Xiaojin , Wang Wencheng , Liu Yunlong
Published: October 2020

Plenty of research achievements on finite‐time stability of discrete‐time switched systems have been reported; however, there are a few results referred to finite‐time unstable subsystems. The design of the average dwell time was not considered alone for finite‐time unstable subsystems in the existing literature. The problems of finite‐time stability and finite‐time boundedness are investigated respectively for a class of discrete‐time switched nonlinear systems with partial finite‐time unstable modes. By using multiple Lyapunov‐like functions, sufficient conditions are derived respectively to ensure that such systems are finite‐time stable and finite‐time bounded based on an improved mode‐dependent average dwell time and iteration technique. Depending on the above results, sufficient conditions, which can guarantee discrete‐time switched linear systems finite‐time stable and finite‐time bounded, are obtained respectively by using matrix inequalities. Finally, numerical examples are given to verify the effectiveness of the proposed methods.
Investigation of lanthanum‐sensitized CaZrO3 blue nanophosphors for white light‐emitting diode applications
Authors: Azeem P. Abdul , Evangeline B. , Haranath D. , Rao R. Prasada
Published: October 2020

In the present study, CaZrO3 nanophosphors were sensitized with lanthanum (La) at different concentrations (0.5, 1.0, 1.5, 2.0, and 2.5) prepared using polyvinyl alcohol as the chelating agent through the sol–gel method. To study their structural and optical properties, samples were characterized by X‐ray diffractometry (XRD), field emission scanning electron microscopy (FE‐SEM), transmission electron microscopy (TEM) and photoluminescence (PL). The XRD results revealed that samples were well crystallized and average crystallite sizes were calculated. The average crystallite size value was in good agreement with the value obtained from TEM analysis. Energy dispersive spectroscopy and FE‐SEM confirmed the existence of La in the prepared samples. In the PL spectra, La‐sensitized samples exhibited three bands at 402 nm, 438 nm, and 463 nm in the visible range when excited at the 260 nm wavelength. As the proportion of La increased, the intensity of bands at 438 nm and 463 nm decreased, whereas the band at 402 nm remained stable. Time‐resolved PL spectra illustrated the lifetime of the samples. Corresponding CIE co‐ordinates for La‐sensitized CaZrO3 were calculated.
Improving Antibody Production in Stably Transfected CHO Cells by CRISPR‐Cas9‐Mediated Inactivation of Genes Identified in a Large‐Scale Screen with Chinese Hamster‐Specific siRNAs
Authors: Lin Pao‐Chun , Liu Ren , Alvin Krista , Wahyu Shahreel , Murgolo Nicholas , Ye Jianxin , Du Zhimei , Song Zhiwei
Published: October 2020

The Chinese hamster ovary (CHO) cell line is commonly used for the production of biotherapeutics. As cell productivity directly affects the cost of production, methods are developed to manipulate the expression of specific genes that are known to be involved in protein synthesis, folding, and secretion to increase productivity. However, there are no large‐scale CHO‐specific functional screens to identify novel gene targets that impact the production of secreted recombinant proteins. Here, a large‐scale, CHO cell‐specific small interfering RNA screen is performed to identify genes that consistently enhance antibody production when silenced in a panel of seven CHO cell lines. Four genes, namely, Cyp1a2, Atp5s, Dgki, and P3h2, are identified, and then selected for CRISPR‐Cas9 knockout validation in recombinant CHO cell lines. Single knockout of Cyp1a2, Atp5s, or Dgki, but not P3h2, results in a more than 90% increase in specific antibody productivity. Overall, the knockout of Cyp1a2 demonstrates the most significant improvement of antibody production, with a minimal impact on cell growth.
Students engage in primary literature in molecular biology techniques using an online journal club format
Authors: Oxford Julia Thom , Jorcyk Cheryl L.
Published: October 2020

Campus closures in Spring 2020 required rapid transition to online course delivery. Fall 2020 has similar needs and expectations. The Advanced Topics in Molecular Biology Techniques course, designed for upper division undergraduate and graduate students, uses a “journal club” format. The journal club format includes practice‐based learning and provides student choice. Examples from graduate students effectively model the expectations using near‐peer instruction. Teaching in the time of COVID‐19 requires openness to new ideas and modifications to previous approaches. We were able to move the course online with little interruption.
The impact of heuristic availability bias on investmentdecision‐making: Moderated mediation model
Authors: Salman Muhammad , Khan Bakhtiar , Khan Sher Zaman , Khan Rafi Ullah
Published: October 2020

This study tends to examine the moderated mediation role of external locus of control (ELC) and risk tolerance (RT) in the relationship between heuristic availability bias (HAB) and investment decision‐making (IDM). We used SPSS PROCESS Model 7 (moderated mediation) on a data set gleaned from 385 practicing stock investors at Pakistan Stock Exchange. The results of the study revealed that the relationship between HAB and IDM is partially mediated by RT, whereas, the ELC significantly moderates the relationship between HAB and RT. Moreover, in the case of moderated mediation, the ELC showed a significant moderating role in the relationship of HAB with IDM through RT. Since the findings of the study argue that ELC intensifies the influence of HAB on investors' risk‐taking propensity that inculcate them toward making investment decisions. The practical and theoretical implications of the study are discussed in detail.
Cognitive‐affective drivers of fixation in threat assessment
Authors: Meloy J. Reid , Rahman Tahir
Published: October 2020

Pathological fixation – preoccupation with a person or a cause that is accompanied by deterioration in social and occupational functioning – has been found to precede most cases of targeted violence. It is clinically observed and theorized to have three different cognitive‐affective drivers: delusion, obsession, or extreme overvalued belief. Each driver is explained, and case examples are provided in the context of threat assessment. Extreme overvalued belief as a new concept is discussed in detail, both its historical provenance and its demarcation from delusions and obsessions. Threat management for each separate cognitive‐affective driver is briefly summarized, based upon current clinical findings and research. Emphasis is placed upon understanding both the categorical and dimensional nature (intensity) of these cognitive‐affective drivers, and suggested guidelines are offered for the assessment of such in a clinical examination by a forensic psychiatrist or psychologist.
Hydrogen Sulfide Oxidation by Sulfide Quinone Oxidoreductase
Authors: Landry Aaron P. , Ballou David P. , Banerjee Ruma
Published: October 2020

Hydrogen sulfide (H2S) is an environmental toxin and a heritage of ancient microbial metabolism that has stimulated new interest following its discovery as a neuromodulator. While many physiological responses have been attributed to low H2S levels, higher levels inhibit complex IV in the electron transport chain. To prevent respiratory poisoning, a dedicated set of enzymes that make up the mitochondrial sulfide oxidation pathway exists to clear H2S. The committed step in this pathway is catalyzed by sulfide quinone oxidoreductase (SQOR), which couples sulfide oxidation to coenzyme Q10reduction in the electron transport chain. The SQOR reaction prevents H2S accumulation and generates highly reactive persulfide species as products; these can be further oxidized or can modify cysteine residues in proteins by persulfidation. Here, we review the kinetic and structural characteristics of human SQOR, and how its unconventional redox cofactor configuration and substrate promiscuity lead to sulfide clearance and potentially expand the signaling potential of H2S. This dual role of SQOR makes it a promising target for H2S‐based therapeutics.
PSPH induces cell autophagy and promotes cell proliferation and invasion in the hepatocellular carcinoma cell line Huh7 via the AMPK/mTOR/ULK1 signaling pathway
Authors: Zhang Jianli , Wang Erhao , Zhang Lei , Zhou Bo
Published: October 2020

Phosphoserine phosphatase (PSPH), a key enzyme of the l‐serine synthesis pathway, has been involved in cancer progression and survival. However, limited evidence revealed the PSPH influence on hepatocellular carcinoma (HCC). Herein, we observed that PSPH expression was upregulated in both HCC tissues and cell lines, which was determined by western blotting. TCGA database showed that the PSPH protein levels were significantly upregulated and affected patient survival rates in HCC. Then gain‐ and loss‐of‐function manipulations were performed by transfection with a pcDNA‐PSPH expression vector or a specific short interfering RNA against PSPH in Huh7 cells. Huh7 cell proliferation, stemness, invasion, and apoptosis were assessed by using CCK‐8 test, colony formation assay, Transwell assay, and Flow cytometry analysis, respectively, and levels of autophagy‐related proteins were detected by using western blotting. The results showed that PSPH could induce Huh7 cell autophagy, promote cell proliferation and invasion, and inhibit apoptosis. The knockdown of PSPH could inhibit Huh7 cell proliferation, invasion, and autophagy. Furthermore, PSPH activated Liver kinase B1 (LKB1) and TGF beta‐activated kinase 1 (TAK1), affected the adenosine 5′‐monophosphate‐activated protein kinase (AMPK)/mTOR/ULK1 signaling pathway, but could not activate calcium/calmodulin‐dependent protein kinase kinase (CaMKK) in Huh7 cells. Inhibition of either LKB1, TAK1, or AMPK could eliminate the effect of PSPH overexpression on Huh7 cell behaviors. However, inhibition of CaMKK could not influence the effect of PSPH overexpression on Huh7 cell behaviors. In conclusion, PSPH could induce autophagy, promote proliferation and invasion, and inhibit apoptosis in HCC cells via the AMPK/mTOR/ULK1 signaling pathway.
Isolation of a 16π‐Electrons 1,4‐Diphosphinine‐1,4‐diide with a Planar C4P2Ring
Authors: Rottschäfer Dennis , Neumann Beate , Stammler Hans‐Georg , Sergeieva Tetiana , Andrada Diego M. , Ghadwal Rajendra S.
Published: October 2020

Herein, we report the first 1,4‐diphosphinine‐1,4‐diide compound [(ADCPh)P]2(5‐Ph) (ADCPh=PhC{(NDipp)C}2; Dipp=2,6‐iPr2C6H3) derived from an anionic dicarbene (ADCPh) as a red crystalline solid. Compound5‐Phcontaining a 16π‐electron planar fused‐tricyclic ring system was obtained by the 4e reduction of [(ADCPh)PCl2]2(4‐Ph) with Mg (or KC8) in a quantitative yield. Experimental and computational results imply that the central 8π‐electrons C4P2ring of5‐Ph, which is fused between two 6π‐electrons C3N2aromatic rings, is antiaromatic. Thus, each of the phosphorus atoms of5‐Phhas two electron‐lone‐pairs, one in a p‐type orbital is in conjugation with the C=C bonds of the C4P2ring, while the second resides in a σ‐symmetric orbital. This can be shown with the gold complex [(ADCPh)P(AuCl)2]2(6‐Ph) obtained by reacting5‐Phwith (Me2S)AuCl. A mixture of5‐Phand4‐Phundergoes comproportionation in the presence of MgCl2to form the intermediate oxidation state compound [(ADCAr)P]2(MgCl4) (7‐Ph), which is an aromatic species.
Synthesis of Morpholine‐Based Analogues of (−)‐Zampanolide and Their Biological Activity
Authors: Bold Christian Paul , Gut Melanie , Schürmann Jasmine , Lucena‐Agell Daniel , Gertsch Jürg , Díaz José Fernando , Altmann Karl‐Heinz
Published: October 2020

We describe the convergent synthesis of three prototypical examples of a new class of analogues of the complex, cytotoxic marine macrolide (−)‐zampanolide that incorporate an embedded N‐substituted morpholine moiety in place of the natural tetrahydropyran ring. The final construction of the macrolactone core was based on a high‐yielding intramolecular HWE olefination, while the hemiaminal‐linked side chain was elaborated through a stereoselective, BINAL‐H‐mediated addition of (Z,E)‐sorbamide to a macrocyclic aldehyde precursor. The synthesis of the common functionalized morpholine building block involved two consecutive epoxide openings with tosylamide and the product of the first opening reaction, respectively, as nucleophiles. Of the three morpholino‐zampanolides investigated, the N‐acetyl and the N‐benzoyl derivatives both exhibited nanomolar antiproliferative activity, thus being essentially equipotent with the natural product. In contrast, the activity of the N‐tosyl derivative was significantly reduced.
Strain Release Chemistry of Photogenerated Small‐Ring Intermediates
Authors: Luque Adriana , Paternoga Jan , Opatz Till
Published: October 2020

Photochemical processes, such as isomerizations and cycloadditions, have proven to be very useful in the construction of highly strained molecular frameworks. Photoinduced ring strain enables subsequent exergonic reactions which do not require the input of additional chemical energy and provides a variety of attractive synthetic options leading to complex structures. This review covers the progress achieved in the application of sequences combining excitation by ultraviolet light to form strained intermediates, which are further transformed to lower energy products in strain‐release reactions. As ring strain is considerable in small ring systems, photogenerated three‐ and four‐membered rings will be covered, mainly focusing on examples from 2000 to May 2020.
Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from theATHENAstudy
Authors: Blomström‐Lundqvist Carina , Marrouche Nassir , Connolly Stuart , Corp dit Genti Valérie , Wieloch Mattias , Koren Andrew , Hohnloser Stefan H.
Published: October 2020

Background

Atrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history.

Hypothesis

Outcomes with dronedarone may also be impacted by duration of AF/AFL history.

Methods

In this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24 months (intermediate), and ≥ 24 months (long).

Results

Of 2859 patients with data on duration of AF/AFL history, 45.3%, 29.6%, and 25.1% had short, intermediate, and long histories, respectively. Patients in the long history group had the highest prevalence of structural heart disease and were more likely to be in AF/AFL at baseline. Placebo‐treated patients in the long history group also had the highest incidence of AF/AFL recurrence and cardiovascular (CV) hospitalization during the study. The risk of first CV hospitalization/death from any cause was lower with dronedarone vs placebo in patients with short (hazard ratio, 0.79 [95% confidence interval: 0.65‐0.96]) and intermediate (0.72 [0.56‐0.92]) histories; a trend favoring dronedarone was also observed in patients with long history (0.84 [0.66‐1.07]). A similar pattern was observed for first AF/AFL recurrence. No new drug‐related safety issues were identified.

Conclusions

Patients with long AF/AFL history had the highest burden of AF/AFL at baseline and during the study. Dronedarone significantly improved efficacy vs placebo in patients with short and intermediate AF/AFL histories. While exploratory, these results support the potential value in initiating rhythm control treatment early in patients with AF/AFL.
Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double‐blinded randomized controlled trial from the Children's Oncology Group
Authors: Zerr Danielle M. , Milstone Aaron M. , Dvorak Christopher C. , Adler Amanda L. , Chen Lu , Villaluna Doojduen , Dang Ha , Qin Xuan , Addetia Amin , Yu Lolie C. , Conway Keller Mary , Esbenshade Adam J. , August Keith J. , Fisher Brian T. , Sung Lillian
Published: October 2020

Background

To the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line–associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited.

Methods

In the current multicenter, randomized, double‐blind, placebo‐controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once‐daily bathing with 2% CHG‐impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI. Secondary endpoints included total positive blood cultures, acquisition of resistant organisms, and acquisition of cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration.

Results

The study was stopped early because of poor accrual. Among the 177 enrolled patients, 174 were considered as evaluable (88 were randomized to the CHG group and 86 were randomized to the control group). The rate of CLABSI per 1000 central line days in the CHG group was 5.44 versus 3.10 in the control group (risk difference, 2.37; 95% confidence interval, 0.05‐4.69 [P = .049]). Post hoc conditional power analysis demonstrated a 0.2% chance that the results would have favored CHG had the study fully enrolled. The rate of total positive blood cultures did not differ between groups (risk difference, 2.37; 95% confidence interval, −0.41 to 5.14 [P = .078]). The number of patients demonstrating the new acquisition of resistant organisms did not differ between groups (P = .54). Patients in the CHG group were found to be more likely to acquire cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration (P = .032).

Conclusions

The data from the current study do not support the use of routine CHG bathing in children with cancer or those undergoing allogeneic HCT.
The personal visions of physical education student teachers: putting the education at the heart of physical education
Authors: Jess Mike , McMillan Paul , Carse Nicola , Munro Karen
Published: October 2020

With neo‐liberal policies dominating across the world, the marketisation and outsourcing of physical education is now common. Within this context, we argue the need for a ‘shifting perspectives’ agenda that will firmly establish the educational credentials of physical education in the future. Accordingly, we present the view that the ‘curriculum voice’ of physical education teachers will be central in mounting a challenge to this neo‐liberal agenda. In this first study within a longitudinal project, the focus is on final year student teachers studying an undergraduate degree in physical education. Using ecological concepts, we analysed 20 student essays as they seek to describe their personal visions for physical education. Acknowledging the aspirational nature of these visions, findings reveal that each student vision was influenced by different ecological factors and was subsequently personalised. The findings also reveal that while there may be overarching similarities across the visions, the educational subcomponents and theoretical constructs that make up these visions differ across all students. In conclusion, we argue that the findings suggest that, if supported and developed in the future, that these student visions may indeed turn into the ‘curriculum voice’ of a ‘shifting perspectives’ agenda.
Molecular Understanding of Charge Storage in MoS2 Supercapacitors with Ionic Liquids
Authors: Liang Zhun , Zhao Chang , Zhao Wei , Zhang Yuan , Srimuk Pattarachai , Presser Volker , Feng Guang
Published: October 2020

Owing to high electrical conductivity and ability to reversibly host a variety of inserted ions, 2D metallic molybdenum disulfide (1T‐MoS2) has demonstrated promising energy storage performance when used as a supercapacitor electrode. However, its charge storage mechanism is still not fully understood, in particular, how the interlayer spacing of 1T‐MoS2 would affect its capacitive performance. In this work, molecular dynamics simulations of 1T‐MoS2 with interlayer spacing ranging from 0.615 to 1.615 nm have been performed to investigate the resulting charge storage capacity in ionic liquids. Simulations reveal a camel‐like capacitance‐potential relation, and MoS2 with an interlayer spacing of 1.115 nm has the highest volumetric and gravimetric capacitance of 118 F cm−3 and 42 F g−1, respectively. Although ions in MoS2 with an interlayer spacing of 1.115 nm diffuse much faster than with interlayer spacings of 1.365 and 1.615 nm, the MoS2 with larger interlayer spacing has a much faster‐charging process. Our analyses reveal that the ion number density and its charging speed, as well as ion motion paths, have significant impacts on the charging response. This work helps to understand how the interlayer spacing affects the interlayer ion structures and the capacitive performance of MoS2, which is important for revealing the charge storage mechanism and designing MoS2 supercapacitor.
Cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 are lower in asymptomatic than symptomatic COVID‐19 patients
Authors: Mazzoni Alessio , Maggi Laura , Capone Manuela , Spinicci Michele , Salvati Lorenzo , Colao Maria Grazia , Vanni Anna , Kiros Seble Tekle , Mencarini Jessica , Zammarchi Lorenzo , Mantengoli Elisabetta , Menicacci Lorenzo , Caldini Eleonora , Romagnani Sergio , Liotta Francesco , Morettini Alessandro , Rossolini Gian Maria , Bartoloni Alessandro , Cosmi Lorenzo , Annunziato Francesco
Published: October 2020

The characterization of cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 is fundamental to understand COVID‐19 progression and the development of immunological memory to the virus. In this study, we detected T‐cells reactive to SARS‐CoV‐2 proteins M, S, and N, as well as serum virus‐specific IgM, IgA, IgG, in nearly all SARS‐CoV‐2 infected individuals, but not in healthy donors. Virus‐reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immune‐checkpoint molecules PD1 and TIGIT. Of note, we detected antigen‐specific adaptive immune response both in asymptomatic and symptomatic SARS‐CoV‐2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell‐mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life‐threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies.
Ionic Liquid and f‐MWCNTs Fabricated Glassy Carbon Electrode for Determination of Amygdalin in Apple Seeds
Authors: Chokkareddy Rajasekhar , Redhi Gan G
Published: October 2020

This work proposes a novel electrochemical sensor based on functionalised multiwalled carbon nanotubes (f‐MWCNTs), zinc oxide nanoparticles (ZnONPs), and (methyltrioctylammonium chloride ionic liquid (IL)) fabricated glassy carbon electrode (GCE), for the determination of amygdalin (AMY) in apple seeds. X‐ray diffraction (XRD), Brunauer‐Emmett‐Teller (BET), Fourier‐transform infrared spectroscopy (FT‐IR), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA) as well as electrochemical impedance spectroscopy (EIS) techniques were used to characterize the synthesized ZnONPs and its nanocomposite. EIS and differential Pulse Voltammetry (DPV) was utilized to investigate the electrochemical behavior of AMY on the IL‐ZnONPs‐f‐MWCNTs nanocomposite modified GCE. The linear range response is obtained from 0.012–6 μM for AMY determination under optimized experimental conditions, and the limit of detection (LOD) values were found to be 0.012 μM. The novel method developed was successfully used to determine AMY in spiked apple seed samples with satisfactory results.
Bifunctional Behavior of Pd/Ni Nanocatalysts on MOF‐Derived Carbons for Alkaline Water‐splitting
Authors: Ipadeola Adewale K. , Mwonga Patrick V. , Ray Sekar C. , Maphanga Rapela R. , Ozoemena Kenneth I.
Published: October 2020

Metal‐organic framework derived carbon (MOFDC) serves as supporting platforms for PdNi catalyst (Pd/Ni/MOFDC) and acid‐treated nickel counterpart (Pd/AT‐Ni/MOFDC). The two Pd‐based electrocatalysts are tested for alkaline water‐splitting (i. e., hydrogen evolution (HER) and oxygen evolution reactions (OER)). The results reveal better HER and OER kinetics for Pd/Ni/MOFDC than Pd/AT‐Ni/MOFDC. DFT calculations show that the high performance of the Pd/Ni/MOFDC can be associated with its high conductivity toward adsorbed OH compared to the Pd/AT‐Ni/MOFDC counterpart. The superior overall water‐splitting of Pd/Ni/MOFDC describes the synergy between Ni/Ni(OH)2 interface and nanostructured Pd for possible future application in an electrolyzer.
Tall building performance‐based seismic design using SCEC broadband platform site‐specific ground motion simulations
Authors: Zhong Kuanshi , Lin Ting , Deierlein Gregory G. , Graves Robert W. , Silva Fabio , Luco Nicolas
Published: October 2020

The scarcity of strong ground motion records presents a challenge for making reliable performance assessments of tall buildings whose seismic design is controlled by large‐magnitude and close‐distance earthquakes. This challenge can be addressed using broadband ground‐motion simulation methods to generate records with site‐specific characteristics of large‐magnitude events. In this paper, simulated site‐specific earthquake seismograms, developed through a related project that was organized through the Southern California Earthquake Center (SCEC) Ground Motion Simulation Validation (GMSV) Technical Activity Group, are used for nonlinear response history analyses of two archetype tall buildings for sites in San Francisco, Los Angeles, and San Bernardino. The SCEC GMSV team created the seismograms using the Broadband Platform (BBP) simulations for five site‐specific earthquake scenarios. The two buildings are evaluated using nonlinear dynamic analyses under comparable record suites selected from the simulated BBP catalog and recorded motions from the NGA‐West database. The collapse risks and structural response demands (maximum story drift ratio, peak floor acceleration, and maximum story shear) under the BBP and NGA suites are compared. In general, this study finds that use of the BBP simulations resolves concerns about estimation biases in structural response analysis which are caused by ground motion scaling, unrealistic spectral shapes, and overconservative spectral variations. While there are remaining concerns that strong coherence in some kinematic fault rupture models may lead to an overestimation of velocity pulse effects in the BBP simulations, the simulations are shown to generally yield realistic pulse‐like features of near‐fault ground motion records.
Selection on a small genomic region underpins differentiation in multiple color traits between two warbler species
Authors: Wang Silu , Rohwer Sievert , de Zwaan Devin R. , Toews David P. L. , Lovette Irby J. , Mackenzie Jacqueline , Irwin Darren
Published: October 2020

Speciation is one of the most important processes in biology, yet the study of the genomic changes underlying this process is in its infancy. North American warbler species Setophaga townsendi and Setophaga occidentalis hybridize in a stable hybrid zone, following a period of geographic separation. Genomic differentiation accumulated during geographic isolation can be homogenized by introgression at secondary contact, whereas genetic regions that cause low hybrid fitness can be shielded from such introgression. Here, we examined the genomic underpinning of speciation by investigating (1) the genetic basis of divergent pigmentation traits between species, (2) variation in differentiation across the genome, and (3) the evidence for selection maintaining differentiation in the pigmentation genes. Using tens of thousands of single nucleotide polymorphisms (SNPs) genotyped in hundreds of individuals within and near the hybrid zone, genome-wide association mapping revealed a single SNP associated with cheek, crown, breast coloration, and flank streaking, reflecting pleiotropy (one gene affecting multiple traits) or close physical linkage of different genes affecting different traits. This SNP is within an intron of the RALY gene, hence we refer to it as the RALY SNP. We then examined between-species genomic differentiation, using both genotyping-by-sequencing and whole genome sequencing. We found that the RALY SNP is within one of the highest peaks of differentiation, which contains three genes known to influence pigmentation: ASIP, EIF2S2, and RALY (the ASIP-RALY gene block). Heterozygotes at this gene block are likely of reduced fitness, as the geographic cline of the RALY SNP has been narrow over two decades. Together, these results reflect at least one barrier to gene flow within this narrow (∼200 kb) genomic region that modulates plumage difference between species. Despite extensive gene flow between species across the genome, this study provides evidence that selection on a phenotype-associated genomic region maintains a stable species boundary.
Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery
Authors: Starlinger Patrick , Pereyra David , Hackl Hubert , Ortmayr Gregor , Braunwarth Eva , Santol Jonas , Najarnia Sina , Driedger Michael R. , Gregory Lindsey , Alva‐Ruiz Roberto , Glasgow Amy , Assinger Alice , Nagorney David M. , Habermann Elizabeth B. , Staetttner Stefan , Cleary Sean P. , Smoot Rory L. , Gruenberger Thomas
Published: October 2020

Background and Aims

Platelet‐stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin’s impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection.

Approach and Results

Consecutive patients undergoing hepatic resection (n = 754) were retrospectively included from prospectively maintained databases from two European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRIs/SNRIs was recorded, and patients were followed up for postoperative liver dysfunction (LD), morbidity, and mortality. Perioperative intraplatelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRIs/SNRIs showed a higher incidence of morbidity, severe morbidity, LD, and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio [OR], 1.56; 95% confidence interval [CI], 1.07‐2.31; severe morbidity OR, 1.86; 95% CI, 1.22‐2.79; LD OR, 1.96; 95% CI, 1.23‐3.06; LD requiring intervention OR, 2.22; 95% CI, 1.03‐4.36). Further, multivariable analysis confirmed the independent association of SSRIs/SNRIs with postoperative LD, which was closely associated with postoperative 90‐day mortality and 1‐year overall survival.

Conclusions

We observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRIs/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.