bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanomolar potency of imidazo[2,1‐b]thiazole analogs as indoleamine 2,3‐dioxygenase inhibitors
Authors: Ewida Menna A. , Ewida Heba A. , Ahmed Mahmoud S. , Allam Heba Abdelrasheed , ElBagary Ramzia I. , George Riham F. , Georgey Hanan H. , El‐Subbagh Hussein I.
Published: July 2021

Novel series of imidazo[2,1‐b]thiazole analogs were designed, synthesized, and biologically evaluated as indoleamine 2,3‐dioxygenase (IDO1) inhibitors. Imidazo[2,1‐b]thiazoles 6, 7, and 8 showed inhibitory profiles against IDO1 at IC50 values of 68.48, 82.39, and 48.48 nM, respectively, compared with IDO5L at IC50 67.40 nM. Benzo[d]imidazo[2,1‐b]thiazoles 17, 20, and 22 showed promising IDO1 inhibition at IC50 values of 53.58, 53.16, and 57.95 nM, respectively. Compound 7 showed a growth‐inhibitory profile at GI of 39.33% against the MCF7 breast cancer cell line, while 8 proved lethal to ACHN renal cancer cells. Cells treated with compounds 17 and 22 showed a typical apoptosis pattern of DNA fragments that reflected the G0/G1, S, and G2/M phases of the cell cycle, together with a pre‐G1 phase corresponding to apoptotic cells, which indicates that cell growth arrest occurred at the S phase. Molecular modeling simulations validated the potential of benzo[d]imidazo[2,1‐b]thiazole analogs to chelate iron(III) within the IDO1 binding pocket and, hence, to have a better binding affinity via hydrophobic–hydrophobic interactions.
A Photoluminescent Ag10Cu6 Cluster Stablized by a PNNP Ligand and Phenylacetylides Selectively and Reversibly Senses Ammonia in Air and Water
Authors: Wang Yuwei , Yan Jia‐Jun , Hu Shengnan , James Young David , Li Hong‐Xi , Ren Zhi‐Gang
Published: July 2021

A photoluminescent bimetallic cluster [Ag10Cu6(bdppthi)2(C≡CPh)12(MeOH)2(H2O)](ClO4)4 (1, bdppthi=N,N’‐bis(diphenylphosphanylmethyl)‐tetrahydroimidazole} was synthesized from the PNNP type ligand bdppthi generated in‐situ. Upon excitation at 365 nm, 1 exhibited strong phosphorescent emission at 630 nm, which was selectively quenched by NH3 in air or water. The sensing of NH3 was rapid and recoverable, with detection limits of 53 ppm (v/v) in N2 and 21 μmol/L (0.36 ppm, w/w) for NH3 ⋅ H2O in water. Cluster 1 could potentially serve as a bifunctional chemical sensor for the efficient detection of ammonia in waste‐gas and waste‐water.
Amides Activation: Transition Metal‐Free Coupling Between CN Activated Amides and Enolizable Amides
Authors: Joseph Devaneyan , Oh Min Seok , Jayaraman Aravindan , Lee Sunwoo
Published: July 2021

Transition metal‐free Claisen‐type condensation between two different amides was developed. N‐phenyl‐N‐tosylbenzamide derivatives reacted with enolizable amides such as N‐methyl pyrrolidinone and N,N‐dimethyl acetamide in the presence of NaHMDS to give their corresponding β‐ketoamides with moderate‐to‐good yields.
NO Electroreduction by Transition Metal Dichalcogenides with Chalcogen Vacancies
Authors: Tursun Mamutjan , Wu Chao
Published: July 2021

Nitric oxide electroreduction reaction (NOER) is one of the most attractive routes for ammonia synthesis and NOx‐related pollutant treatment. However, current research on NOER catalysts mainly focus on noble metals and single atom catalysts, while low‐cost transition metal dichalcogenides (TMDs) are rarely considered, let alone their product selectivity. Herein, using first‐principles calculations, we systematically investigate the performance of a series of single‐layer TMDs (MoS2, MoSe2, MoTe2, TaTe2 and WTe2) in the 1T’ phase as electrocatalysts for NOER. Our results reveal that defective 1T’‐MoS2 and 1T’‐MoSe2 monolayers (with the most common sulphur and selenium vacancies, respectively) exhibit excellent activity for NOER as well as high selectivity for ammonia, which can be correspondingly yielded at 0 and −0.06 V potentials, comparable to the best Pt‐based and single atom catalysts. Furthermore, these two catalysts efficiently suppress the competing hydrogen evolution reaction (HER). Thus, single‐layer TMDs synthesized with chalcogen vacancies may serve as efficient catalysts for electrochemical ammonia synthesis from pollutants and electrocatalytic denitrification.
Ternary Conductance Switching Realized by a Pillar[5]arene‐Functionalized Two‐Dimensional Imine Polymer Film
Authors: Song Yaru , Feng Guangyuan , Sun Chenfang , Liang Qiu , Wu Lingli , Yu Xi , Lei Shengbin , Hu Wenping
Published: July 2021

Nowadays, most manufacturing memory devices are based on materials with electrical bistability (i. e., “0” and “1”) in response to an applied electric field. Memory devices with multilevel states are highly desired so as to produce high‐density and efficient memory devices. Herein, we report the first multichannel strategy to realize a ternary‐state memristor. We make use of the intrinsic sub‐nanometer channel of pillar[5]arene and nanometer channel of a two‐dimensional imine polymer to construct an active layer with multilevel channels for ternary memory devices. Low threshold voltage, long retention time, clearly distinguishable resistance states, high ON/OFF ratio (OFF/ON1/ON2=1 : 10 : 103), and high ternary yield (75 %) were obtained. In addition, the flexible memory device based on 2DPTPAZ+TAPB can maintain its stable ternary memory performance after being bent 500 times. The device also exhibits excellent thermal stability and can tolerate a temperature as high as 300 °C. It is envisioned that the results of this work will open up possibilities for multistate, flexible resistive memories with good thermal stability and low energy consumption, and broaden the application of pillar[n]arene.
Facile Synthesis of Platinum Right Bipyramids by Separating and Controlling the Nucleation Step in a Continuous Flow System
Authors: Chen Ruhui , Shi Yifeng , Xie Minghao , Xia Younan
Published: July 2021

Colloidal synthesis of metal nanocrystals with controlled shapes and internal structures calls for a tight control over both the nucleation and growth processes. Here we report a method for the facile synthesis of Pt right bipyramids (RBPs) by separating nucleation from growth and controlling the nucleation step in a continuous flow reactor. Specifically, homogeneous nucleation was thermally triggered by introducing the reaction solution into a tubular flow reactor held at an elevated temperature to generate singly‐twinned seeds. At a lower temperature, the singly‐twinned seeds were protected from oxidative etching to allow their slow growth and evolution into RBPs while additional nucleation of undesired seeds could be largely suppressed to ensure RBPs as the main product. Further investigation indicated that the internal structure and growth pattern of the seeds were determined by the temperatures used for the nucleation and growth steps, respectively. The Br− ions involved in the synthesis also played a critical role in the generation of RBPs by serving as a capping agent for the Pt{100} facets while regulating the reduction kinetics through coordination with the Pt(IV) ions.
Efficient Entropy‐Driven Inhibition of Dipeptidyl Peptidase III by Hydroxyethylene Transition‐State Peptidomimetics
Authors: Ivkovic Jakov , Jha Shalinee , Lembacher‐Fadum Christian , Puschnig Johannes , Kumar Prashant , Reithofer Viktoria , Gruber Karl , Macheroux Peter , Breinbauer Rolf
Published: July 2021

Dipeptidyl peptidase III (DPP3) is a ubiquitously expressed Zn‐dependent protease, which plays an important role in regulating endogenous peptide hormones, such as enkephalins or angiotensins. In previous biophysical studies, it could be shown that substrate binding is driven by a large entropic contribution due to the release of water molecules from the closing binding cleft. Here, the design, synthesis and biophysical characterization of peptidomimetic inhibitors is reported, using for the first time an hydroxyethylene transition‐state mimetic for a metalloprotease. Efficient routes for the synthesis of both stereoisomers of the pseudopeptide core were developed, which allowed the synthesis of peptidomimetic inhibitors mimicking the VVYPW‐motif of tynorphin. The best inhibitors inhibit DPP3 in the low μM range. Biophysical characterization by means of ITC measurement and X‐ray crystallography confirm the unusual entropy‐driven mode of binding. Stability assays demonstrated the desired stability of these inhibitors, which efficiently inhibited DPP3 in mouse brain homogenate.
Aminotroponiminates: Impact of the NO2 Functional Group on Coordination, Isomerisation, and Backbone Substitution
Authors: Hanft Anna , Rottschäfer Dennis , Wieprecht Nele , Geist Felix , Radacki Krzysztof , Lichtenberg Crispin
Published: July 2021

Aminotroponiminate (ATI) ligands are a versatile class of redox‐active and potentially cooperative ligands with a rich coordination chemistry that have consequently found a wide range of applications in synthesis and catalysis. While backbone substitution of these ligands has been investigated in some detail, the impact of electron‐withdrawing groups on the coordination chemistry and reactivity of ATIs has been little investigated. We report here Li, Na, and K salts of an ATI ligand with a nitro‐substituent in the backbone. It is demonstrated that the NO2 group actively contributes to the coordination chemistry of these complexes, effectively competing with the N,N‐binding pocket as a coordination site. This results in an unprecedented E/Z isomerisation of an ATI imino group and culminates in the isolation of the first “naked” (i. e., without directional bonding to a metal atom) ATI anion. Reactions of sodium ATIs with silver(I) and tritylium salts gave the first N,N‐coordinated silver ATI complexes and unprecedented backbone substitution reactions. Analytical techniques applied in this work include multinuclear (VT‐)NMR spectroscopy, single‐crystal X‐ray diffraction analysis, and DFT calculations.
A mathematical dashboard for the analysis of Italian COVID‐19 epidemic data
Authors: Parolini Nicola , Ardenghi Giovanni , Dede' Luca , Quarteroni Alfio
Published: July 2021

An analysis of the COVID‐19 epidemic is proposed on the basis of the epiMOX dashboard (publicly accessible at https://www.epimox.polimi.it) that deals with data of the epidemic trends and outbreaks in Italy from late February 2020. Our analysis provides an immediate appreciation of the past epidemic development, together with its current trends by fostering a deeper interpretation of available data through several critical epidemic indicators. In addition, we complement the epiMOX dashboard with a predictive tool based on an epidemiological compartmental model, named SUIHTER, for the forecast on the near future epidemic evolution.
Synthesis and Halochromic Properties of 1,2,6‐Tri‐ and 1,2,3,6‐Tetra‐aryl Azulenes
Authors: Zhu Qiang , Png Zhuang Mao , Lin Tingting , Loh Xian Jun , Tang Tao , Xu Jianwei
Published: July 2021

A series of novel 2,6‐functionalized azulene molecules Azu1‐3 with varied fluorene substituents at the 1‐ and 3‐positions of azulene as well as at the 5’‐position of 2‐thiophene group were synthesized. Their electronic absorption and emission spectra at neutral and protonated states were examined. It was found that after functionalization with fluorenyl groups, Azu1‐3 exhibited absorption maxima at 445, 451 to 468 nm, respectively. In contrast, their corresponding protonated species showed much redshifted absorption maxima at 560, 582 to 643 nm, respectively, mainly due to the extension of conjugation length and the large dipole moment along the C2v axis of 2,6‐substituted azulene molecules. Azu1‐3 are non‐fluorescent in their neutral forms, but became emissive in their protonated states. Analysis of absorption and emission spectra shows that substitution of the 1‐ or 3‐position of azulene led to decrease in response to trifluoroacetic acid.
Restored and remnant Banksia woodlands elicit different foraging behavior in avian pollinators
Authors: Ritchie Alison L. , Elliott Carole P. , Sinclair Elizabeth A. , Krauss Siegfried L.
Published: July 2021

Pollinators and the pollination services they provide are critical for seed set and self‐sustainability of most flowering plants. Despite this, pollinators are rarely assessed in restored plant communities, where their services are largely assumed to re‐establish. Bird–pollinator richness, foraging, and interaction behavior were compared between natural and restored Banksia woodland sites in Western Australia to assess their re‐establishment in restored sites. These parameters were measured for natural communities of varying size and degree of fragmentation, and restored plant communities of high and low complexity for three years, in the summer and winter flowering of Banksia attenuata and B. menziesii, respectively. Bird visitor communities varied in composition, richness, foraging movement distances, and aggression among sites. Bird richness and abundance were lowest in fragmented remnants. Differences in the composition were associated with the size and degree of fragmentation in natural sites, but this did not differ between seasons. Restored sites and their adjacent natural sites had similar species composition, suggesting proximity supports pollinator re‐establishment. Pollinator foraging movements were influenced by the territorial behavior of different species. Using a network analysis approach, we found foraging behavior varied, with more frequent aggressive chases observed in restored sites, resulting in more movements out of the survey areas, than observed in natural sites. Aggressors were larger‐bodied Western Wattlebirds (Anthochaera chrysoptera) and New Holland Honeyeaters (Phylidonyris novaehollandiae) that dominated nectar resources, particularly in winter. Restored sites had re‐established pollination services, albeit with clear differences, as the degree of variability in the composition and behavior of bird pollinators for Banksias in the natural sites created a broad completion target against which restored sites were assessed. The abundance, diversity, and behavior of pollinator services to remnant and restored Banksia woodland sites were impacted by the size and degree of fragmentation, which in turn influenced bird–pollinator composition, and were further influenced by seasonal changes between summer and winter. Consideration of the spatial and temporal landscape context of restored sites, along with plant community diversity, is needed to ensure the maintenance of the effective movement of pollinators between natural remnant woodlands and restored sites.
Intraspecific variation mediates density dependence in a genetically diverse plant species
Authors: Zaiats Andrii , Germino Matthew J. , Serpe Marcelo D. , Richardson Bryce A. , Caughlin T. Trevor
Published: July 2021

Interactions between neighboring plants are critical for biodiversity maintenance in plant populations and communities. Intraspecific trait variation and genome duplication are common in plant species and can drive eco‐evolutionary dynamics through genotype‐mediated plant–plant interactions. However, few studies have examined how species‐wide intraspecific variation may alter interactions between neighboring plants. We investigate how subspecies and ploidy variation in a genetically diverse species, big sagebrush (Artemisia tridentata), can alter the demographic outcomes of plant interactions. Using a replicated, long‐term common garden experiment that represents range‐wide diversity of A. tridentata, we ask how intraspecific variation, environment, and stand age mediate neighbor effects on plant growth and survival. Spatially explicit models revealed that ploidy variation and subspecies identity can mediate plant–plant interactions but that the effect size varied in time and across experimental sites. We found that demographic impacts of neighbor effects were strongest during early stages of stand development and in sites with greater growth rates. Within subspecies, tetraploid populations showed greater tolerance to neighbor crowding compared to their diploid variants. Our findings provide evidence that intraspecific variation related to genome size and subspecies identity impacts spatial demography in a genetically diverse plant species. Accounting for intraspecific variation in studies of conspecific density dependence will improve our understanding of how local populations will respond to novel genotypes and biotic interaction regimes. As introduction of novel genotypes into local populations becomes more common, quantifying demographic processes in genetically diverse populations will help predict long‐term consequences of plant–plant interactions.
A unifying framework for analyzing temporal changes in functional and taxonomic diversity along disturbance gradients
Authors: Larson Erin I. , Poff N. LeRoy , Funk W. Chris , Harrington Rachel A. , Kondratieff Boris C. , Morton Scott G. , Flecker Alexander S.
Published: July 2021

Frameworks exclusively considering functional diversity are gaining popularity, as they complement and extend the information provided by taxonomic diversity metrics, particularly in response to disturbance. Taxonomic diversity should be included in functional diversity frameworks to uncover the functional mechanisms causing species loss following disturbance events. We present and test a predictive framework that considers temporal functional and taxonomic diversity responses along disturbance gradients. Our proposed framework allows us to test different multidimensional metrics of taxonomic diversity that can be directly compared to calculated multidimensional functional diversity metrics. It builds on existing functional diversity–disturbance frameworks both by using a gradient approach and by jointly considering taxonomic and functional diversity. We used previously unpublished stream insect community data collected prior to, and for the two years following, an extreme flood event that occurred in 2013. Using 14 northern Colorado mountain streams, we tested our framework and determined that taxonomic diversity metrics calculated using multidimensional methods resulted in concordance between taxonomic and functional diversity responses. By considering functional and taxonomic diversity together and using a gradient approach, we were able to identify some of the mechanisms driving species losses following this extreme disturbance event.
Efficient Charge Storage in Hierarchically Porous Carbon Foams for Supercapacitor Applications
Authors: Michael M. D. S. , Kesavan K. S. , Prabaharan S. R. S.
Published: July 2021

Compositionally controlled hierarchically porous monolithic carbon foams synthesized via silica hard templating technique are used as electrodes for symmetrical supercapacitors. Fifteen carbon monoliths are prepared by controlling net quantity of modified silica particles per gram of oily phase, the quantity of oil phase (vol%), and the resin concentration (wt%), exhibiting Brunauer–Emmett–Teller (BET) surface area ranging from 700 to 900 m2 g−1 are chosen to study the profound effect of the influence of pore size and its distribution on their capacitive performance in an aqueous electrolyte using cyclic voltammetry (CV), galvanostatic charge/discharge, and impedance spectroscopy techniques. The typical rectangular shape CV profile illustrates the capacitive properties of these carbon foams. It is found that mesopores facilitate the diffusion of electrolyte ions (aqueous potassium hydroxide (KOH)) deep into the micropores by providing transmission line‐like pathways. In contrast, micropores enrich the density of charge separation that determines the magnitude of charge storage across electric double layers leading to high capacitance, 122 F g−1 for hierarchically porous carbon foam, namely 8/70C60. The coin type (form factor CR2032) symmetrical supercapacitor is fabricated using the best performing carbon (8/70C60), yielding high capacitance retention of 98.2% for 20 000 cycles and achieving a good power density of 76.8 kW kg−1.
Intelligent blockchain management for distributed knowledge graphs in IoT 5G environments
Authors: Djenouri Youcef , Srivastava Gautam , Belhadi Asma , Lin Jerry Chun‐Wei
Published: July 2021

This article introduces a new problem of distributed knowledge graph, in IoT 5G setting. We developed an end‐to‐end solution for solving such problem by exploring the blockchain management and intelligent method for producing the better matching of the concepts and relations of the set of knowledge graphs. The concepts and the relations of the knowledge graphs are divided into several components, each of which contains similar concepts and relations. Instead of exploring the whole concepts and the relations of the knowledge graphs, only the representative of these components is compared during the matching process. The framework has outperformed state‐of‐the‐art knowledge graph matching algorithms using different scenarios as input in the experiments. In addition, to confirm the usability of our suggested framework, an in‐depth experimental analysis has been done; the results are very promising in both runtime and accuracy.
Muscone suppresses gastric cancer via regulation of miRNA‐145
Authors: Gao Feng , Yan Shihai , Sun Zheng , Wang Jia
Published: July 2021

This study aims to determine the effects and mechanism of action of muscone on the biological activity of the gastric cancer cell lines SGC‐7901 and MGC‐803 (proliferation, apoptosis, invasion, and migration) in vitro. An optimal muscone concentration was determined using MTT and cell apoptosis tests. The SGC‐7901 and MGC‐803 cells were divided into five groups: normal control, muscone, miRNA, muscone + miRNA, and muscone + miRNA inhibitor. Cell proliferation rate, apoptosis rate, cell cycle phase distribution, number of invading cells, and wound healing rate were compared among the five groups using MTT, flow cytometry, transwell, and wound healing assays. Relative expression levels of the proteins PI3K, AKT, P21, c‐Myc, MMP‐2, and MMP‐9 were measured by Western blot. Compared with the control group, the groups treated with muscone and miRNA showed significantly lower cell proliferation rate, number of invading cells, and wound healing rate (p < .05 for all), but significantly higher rates of cell apoptosis rate and numbers of cells in the G1 phase (p < .05 for all). These groups also showed significantly lower expression of the proteins PI3K, AKT, c‐Myc, MMP‐2, and MMP‐9 but significantly increased expression of the protein P21 (p < .05). Transfecting muscone‐treated SGC‐7901 and MGC‐803 cells with miRNA‐145 inhibitor resulted in a significant recovery of biological activity (p < .05). Muscone suppresses the biological activity of SGC‐7901 and MGC‐803 gastric cancer cells in vitro via regulation of miRNA‐145.
Transient astrocyte‐like NG2 glia subpopulation emerges solely following permanent brain ischemia
Authors: Kirdajova Denisa , Valihrach Lukas , Valny Martin , Kriska Jan , Krocianova Daniela , Benesova Sarka , Abaffy Pavel , Zucha Daniel , Klassen Ruslan , Kolenicova Denisa , Honsa Pavel , Kubista Mikael , Anderova Miroslava
Published: July 2021

Abstract

NG2 glia display wide proliferation and differentiation potential under physiological and pathological conditions. Here, we examined these two features following different types of brain disorders such as focal cerebral ischemia (FCI), cortical stab wound (SW), and demyelination (DEMY) in 3‐month‐old mice, in which NG2 glia are labeled by tdTomato under the Cspg4 promoter. To compare NG2 glia expression profiles following different CNS injuries, we employed single‐cell RT‐qPCR and self‐organizing Kohonen map analysis of tdTomato‐positive cells isolated from the uninjured cortex/corpus callosum and those after specific injury. Such approach enabled us to distinguish two main cell populations (NG2 glia, oligodendrocytes), each of them comprising four distinct subpopulations. The gene expression profiling revealed that a subpopulation of NG2 glia expressing GFAP, a marker of reactive astrocytes, is only present transiently after FCI. However, following less severe injuries, namely the SW and DEMY, subpopulations mirroring different stages of oligodendrocyte maturation markedly prevail. Such injury‐dependent incidence of distinct subpopulations was also confirmed by immunohistochemistry. To characterize this unique subpopulation of transient astrocyte‐like NG2 glia, we used single‐cell RNA‐sequencing analysis and to disclose their basic membrane properties, the patch‐clamp technique was employed. Overall, we have proved that astrocyte‐like NG2 glia are a specific subpopulation of NG2 glia emerging transiently only following FCI. These cells, located in the postischemic glial scar, are active in the cell cycle and display a current pattern similar to that identified in cortical astrocytes. Astrocyte‐like NG2 glia may represent important players in glial scar formation and repair processes, following ischemia.
“Fact or fiction?”: Oral cavity cancer innonsmoking,nonalcoholdrinking patients as a distinct entity—Scoping review
Authors: Adeoye John , Tan Jia Yan , Ip Cheuk Man , Choi Siu‐Wai , Thomson Peter
Published: July 2021

Oral cavity cancer is often described as a lifestyle‐related malignancy due to its strong associations with habitual factors, including tobacco use, heavy alcohol consumption, and betel nut chewing. However, patients with no genetically predisposing conditions who do not indulge in these risk habits are still being encountered, albeit less commonly. The aim of this review is to summarize contemporaneous reports on these nonsmoking, nonalcohol drinking (NSND) patients. We performed database searching to identify relevant studies from January 1, 2000 to March 31, 2021. Twenty‐six articles from 20 studies were included in this study. We found that these individuals were mostly females in their eighth decade with tumors involving the tongue and gingivobuccal mucosa. This review also observed that these patients were likely diagnosed with early stage tumors with overexpression of programmed death‐ligand 1 (PD‐L1) and increased intensity of tumor infiltrating lymphocytes. Treatment response and disease‐specific prognosis were largely comparable between NSND and smoking/drinking patients.
On the systems intelligence of a learning organization: Introducing a new measure
Authors: Törmänen Juha , Hämäläinen Raimo P. , Saarinen Esa
Published: July 2021

We introduce and validate the Organizational Systems Intelligence (OSI) scale, a measurement tool for learning organization, and propose the scale as a useful tool for human resource development (HRD) at the individual level. The scale complements the operationalization of Senge's “Five Disciplines” of the learning organization. OSI provides a new perspective that links employees' perceptions of various seemingly mundane everyday practices with the organizationally desirable effects of a learning organization. The model suggests developmental perspectives that highlight micro‐level behavioral, informal, interactional, and accessible‐to‐all aspects of the learning organization as a route to improvement. Operating in the vernacular and focusing on human experience in organizations, the OSI perspective points to improvement possibilities in and among people in contrast to structural manager‐level constructs. It contributes to HRD literature that explores developmental outcomes and theoretical understanding from human experience in contrast to rank, status, structure, or hierarchy. With its bottom‐up logic as an operationalization of the Sengean learning organization as a form of applied systems thinking, the model introduces an employee‐level perspective of systems thinking in action into the field of HRD. It is demonstrated that with respect to perceived performance, the OSI scale performs equally well as the widely used Dimensions of the Learning Organization Questionnaire.
Modelling ecohydrological feedbacks in forest and grassland plots under a prolonged drought anomaly in Central Europe 2018–2020
Authors: Kleine Lukas , Tetzlaff Doerthe , Smith Aaron , Dubbert Maren , Soulsby Chris
Published: July 2021

Recent studies have highlighted the importance of understanding ecohydrological drought feedbacks to secure water resources under a changing climate and increasing anthropogenic impacts. In this study, we monitored and modelled feedbacks in the soil–plant‐atmosphere continuum to the European drought summer 2018 and the following 2 years. The physically based, isotope‐aided model EcH2O‐iso was applied to generic vegetation plots (forest and grassland) in the lowland, groundwater‐dominated research catchment Demnitzer Millcreek (NE Germany; 66 km2). We included, inter alia, soil water isotope data in the model calibration and quantified changing “blue” (groundwater recharge) and “green” (evapotranspiration) water fluxes and ages under each land use as the drought progressed. Novel plant xylem isotope data were excluded from calibration but were compared with simulated root uptake signatures in model validation. Results indicated inter‐site differences in the dynamics of soil water storage and fluxes with contrasting water age both during the drought and the subsequent 2 years. Forest vegetation consistently showed a greater moisture stress, more rapid recovery and higher variability in root water uptake depths from a generally younger soil water storage. In contrast, the grassland site, which had more water‐retentive soils, showed higher and older soil water storage and groundwater recharge fluxes. The damped storage and flux dynamics under grassland led to a slower return to younger water ages at depth. Such evidence‐based and quantitative differences in ecohydrological feedbacks to drought stress in contrasting soil‐vegetation units provide important insights into Critical Zone water cycling. This can help inform future progress in the monitoring, modelling and development of climate mitigation strategies in drought‐sensitive lowlands.
SARS‐CoV‐2 spike glycoprotein‐reactive T cells can be readily expanded from COVID‐19 vaccinated donors
Authors: Taborska Pavla , Lastovicka Jan , Stakheev Dmitry , Strizova Zuzana , Bartunkova Jirina , Smrz Daniel
Published: July 2021

Introduction

The COVID‐19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS‐CoV‐2) and coronavirus disease 2019 (COVID‐19). However, the vaccine's efficacy can be compromised in patients with immunodeficiencies or the vaccine‐induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID‐19 vaccine, we have investigated a combination of the COVID‐19 vaccination with ex vivo enrichment and large‐scale expansion of SARS‐CoV‐2 spike glycoprotein‐reactive CD4+ and CD8+ T cells.

Methods

SARS‐CoV‐2‐unexposed donors were vaccinated with two doses of the BNT162b2 SARS‐CoV‐2 vaccine. The peripheral blood mononuclear cells of the vaccinated donors were cell culture‐enriched with T cells reactive to peptides derived from SARS‐CoV‐2 spike glycoprotein. The enriched cell cultures were large‐scale expanded using the rapid expansion protocol (REP) and the peptide‐reactive T cells were evaluated.

Results

We show that vaccination with the SARS‐CoV‐2 spike glycoprotein‐based mRNA COVID‐19 vaccine‐induced humoral response against SARS‐CoV‐2 spike glycoprotein in all tested healthy SARS‐CoV‐2‐unexposed donors. This humoral response was found to correlate with the ability of the donors' PBMCs to become enriched with SARS‐CoV‐2 spike glycoprotein‐reactive CD4+ and CD8+ T cells. Using an 11‐day REP, the enriched cell cultures were expanded nearly 1000‐fold, and the proportions of the SARS‐CoV‐2 spike glycoprotein‐reactive T cells increased.

Conclusion

These findings show for the first time that the combination of the COVID‐19 vaccination and ex vivo T cell large‐scale expansion of SARS‐CoV‐2‐reactive T cells could be a powerful tool for developing T cell‐based adoptive cellular immunotherapy of COVID‐19.
Oral health curriculum evaluation tool (OHCET) for primary care training programs
Authors: Savageau Judith A. , Sullivan Kate , Hargraves J. Lee , Silk Hugh
Published: July 2021

Background

Primary care training schools and programs lack a validated tool to assess their oral health curriculum, and researchers lack a tool to compare oral health curricula across programs/schools and different disciplines.

Objective

This study describes the process and results of creating a 15‐item oral health curriculum evaluation tool (OHCET).

Methods

Three‐phased development of the OHCET from 2018 to 2020 including (a) Delphi group/tool development; (b) tool pilot test; and (c) tool validation/cognitive interviews.

Results

A total of 23 program deans/directors participated in the tool validation/cognitive interviews. Summarizing accuracy scores of all 15 items, the mean accuracy score was 87.1. There was a high correlation (0.917) between the program's total score and the program director's self‐assessed competence of their learners at the time of graduation.

Conclusions

The OHCET was validated and can be used in primary care training programs and schools across the country for institutional evaluation and for research purposes. Program directors and deans can also have some confidence that their ability to subjectively assess their learner's oral health knowledge and skills at graduation is accurate.
Micromorphological considerations on Alyssum nezaketiae Aytaç & H. Duman (Brassicaceae), endemic to gypsum habitats from Turkey: An electron microscopic study
Authors: Kayabaş Ayşenur
Published: July 2021

Alyssum nezaketiae is a local endemic species in gypsum habitats of Çankırı province in Turkey. In this study, I used field collected specimens of A. nezaketiae in a scanning electron microscopy examination of vegetative and reproductive structures of A. nezaketiae. The objective of the study was to investigate the micromorphological properties that define the species and that represent its adaptation(s) to the extreme environmental conditions posed by gypsum habitats. The epidermis had one to two rows at transverse sections of leaf and stem. Cortex was composed six to eight rows parenchyma cells at stem. A number of adaptations to xeric habitats were observed, including: dense silvery lepidote hairs on leaves and stems, small leaves, stomata on the lower surfaces of the leaves occurring in stomatal crypts, intense lignification in the central cylinder of the stems, and bundles of sclerenchyma in the pith region of stems. These can be interpreted as gypsophytic characteristics associated with physiological drought. Micromorphological properties of plant parts are discussed in relation to environmental conditions and possible constraint factors occurring in these gypsum habitats. Furthermore, these micromorphological studies contribute important taxonomic characters that are needed to help identify a species whose habitat is under threat from a variety of human activities.
Selective estrogen receptor modulator, tamoxifen, inhibits Zika virus infection
Authors: Grady Scott F. , Pinto Amelia K. , Hassert Mariah , D'Angelo June A. , Brien James D. , Arnatt Christopher K.
Published: July 2021

Zika virus (ZIKV) is an arbovirus belonging to the flaviviridae family with a risk assessment that has been increasing in recent years and was labeled a global health emergency by the World Health Organization in 2016. There are currently no Food and Drug Administration‐approved treatment options available for ZIKV, so expeditious development of treatment options is urgent. To expedite this process, an on‐market drug, tamoxifen (TAM), was selected as a promising candidate for repurposing due to its wide range of biological activities and because it has already been shown to possess activity against hepatitis C virus, a flavivirus in a separate genus. Anti‐ZIKV activity of TAM was assessed by compound screens using an infectious virus and mechanistic details were gleaned from time of addition and virucidal studies. TAM and an active metabolite, 4‐hydroxytamoxifen (TAM‐OH), both showed promising antiviral activity (EC50 ≈9 and 5 µM, respectively) in initial compound screening and up to 8‐h postinfection, though the virucidal assay indicated that they do not possess any direct virucidal activity. Additionally, TAM was assessed for its activity against ZIKV in the human male germ cell line, SEM‐1, due to the sexually transmitted nature of ZIKV owing to its extended survival times in germ cells. Virus titers show diminished replication of ZIKV over 7 days compared to controls. These data indicate that TAM has the potential to be repurposed as an anti‐ZIKV therapeutic and warrants further investigation.
The dynamics of quantitative SARS‐CoV‐2 antispike IgG response to BNT162b2 vaccination
Authors: Kaneko Shun , Kurosaki Masayuki , Sugiyama Toru , Takahashi Yuka , Yamaguchi Yoshimi , Nagasawa Masayuki , Izumi Namiki
Published: July 2021

Vaccination for SARS‐CoV‐2 is necessary to overcome coronavirus disease 2019 (COVID‐19). However, the time‐dependent vaccine‐induced immune response is not well understood. This study aimed to investigate the dynamics of SARS‐CoV‐2 antispike immunoglobulin G (IgG) response. Medical staff participants who received two sequential doses of the BNT162b2 vaccination on days 0 and 21 were recruited prospectively from the Musashino Red Cross Hospital between March and May 2021. The quantitative antispike receptor‐binding domain (RBD) IgG antibody responses were measured using the Abbott SARS‐CoV‐2 IgGII Quant assay (cut off ≥50 AU/ml). A total of 59 participants without past COVID‐19 history were continuously tracked with serum samples. The median age was 41 (22–75) years, and 14 participants were male (23.7%). The median antispike RBD IgG and seropositivity rates were 0 (0–31.1) AU/ml, 0.3 (0–39.5) AU/ml, 529.1 (48.3–8711.4) AU/ml, 18,836.9 (742.2–57,260.4) AU/ml, and 0%, 0%, 98.3%, and 100% on days 0, 3, 14, and 28 after the first vaccination, respectively. The antispike RBD IgG levels were significantly increased after day 14 from vaccination (p < 0.001) The BNT162b2 vaccination led almost all participants to obtain serum antispike RBD IgG 14 days after the first dose.
Critical roles of cytokine storm and secondary bacterial infection in acute kidney injury development in COVID‐19: A multi‐center retrospective cohort study
Authors: Li Xia‐Qing , Liu Han , Meng Yu , Yin Hai‐Yan , Gao Wen‐Yong , Yang Xiao , Xu Dian‐Shuang , Cai Xing‐Dong , Guan Yin , Lerman Lilach O. , Peng Zhi‐Yong , Zhou Hou‐Rong
Published: July 2021

Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID‐19) and is associated with in‐hospital death. We investigated the incidence of AKI in 223 hospitalized COVID‐19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID‐19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID‐19 and 99 with severe COVID‐19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID‐19 and 4.0% for moderate COVID‐19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150–8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361–13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622–22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 10⁹/L, interquartile range [IQR] 11.3 vs. 8.3 × 10⁹/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID‐19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID‐19 patients.
SARS‐CoV‐2 R.1 lineage variants that prevailed in Tokyo in March 2021
Authors: Nagano Katsutoshi , Tani‐Sassa Chihiro , Iwasaki Yumi , Takatsuki Yuna , Yuasa Sonoka , Takahashi Yuta , Nakajima Jun , Sonobe Kazunari , Ichimura Naoya , Nukui Yoko , Takeuchi Hiroaki , Tanimoto Kousuke , Tanaka Yukie , Kimura Akinori , Tohda Shuji
Published: July 2021

The spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, such as B.1.1.7 and B.1.351, has become a crucial issue worldwide. Therefore, we began testing all patients with COVID‐19 for the N501Y and E484K mutations by using polymerase chain reaction (PCR)‐based methods. Nasopharyngeal swab samples from 108 patients who visited our hospital between February and April 2021 were analyzed. The samples were analyzed using reverse transcription‐PCR with melting curve analysis to detect the N501Y and E484K mutations. A part of the samples was also subjected to whole‐genome sequencing (WGS). Clinical parameters such as mortality and admission to the intensive care unit were analyzed to examine the association between increased disease severity and the E484K mutation. The ratio of cases showing the 501N + 484K mutation rapidly increased from 8% in February to 46% in March. WGS revealed that the viruses with 501N + 484K mutation are R.1 lineage variants. Evidence of increased disease severity related to the R.1 variants was not found. We found that the R.1 lineage variants rapidly prevailed in Tokyo in March 2021, which suggests the increased transmissibility of R.1 variants, while they showed no increased severity.
Association between grade brain tumors and the interleukin‐10 receptor subunit alpha based on surface‐enhanced Raman spectroscopy and multivariate analysis
Authors: Kowalska Aneta Aniela , Czaplicka Marta , Nowicka Ariadna B. , Niciński Krzysztof , Piotrowska Aleksandra , Kamińska Agnieszka
Published: July 2021

We present herein a label‐free method based on surface‐enhanced Raman spectroscopy (SERS) that was performed using a silicon‐based SERS platform. The differentiation between primary and secondary brain tumors SERS data was completed partial least squares (PLS) method with a very high 85% of accuracy (in only first and second factors), whereas calculated using principal component analysis (PCA) method gives 74% (in two consecutive components). Additionally, due to the fact that the interleukin‐10 (IL‐10) cytokine receptor may act in cancer as both an immunosuppressive and an immunostimulant factor, the correlation between the tumor grading and the cytokine receptor are presented. Obtained data indicate that the function of IL‐10 cytokine receptor subunit alpha most probably depends or is closely related to the tumor stage.
Changes in the activity of flavanone 3β‐hydroxylase in blueberry fruit during storage in ozone‐enriched atmosphere
Authors: Piechowiak Tomasz , Skóra Bartosz , Sowa Patrycja
Published: July 2021

BACKGROUND

The present study aimed to determine whether the ozonation process affects the flavonoid biosynthesis in highbush blueberry (Vaccinum corymbosum L.) fruit. Flavanone 3β‐hydroxylase (F3H) was used as a marker of the flavonoid biosynthesis pathway. The activity of F3H, the expression of gene encoding F3H and the antioxidant status in blueberries treated with ozone at a concentration of 15 ppm for 30 min, every 12 h of storage, and maintained at 4 °C for 4 weeks were investigated.

RESULTS

The results showed that ozonation process increases the expression of the F3H gene after 1 week of storage, which translates into a higher catalytic capacity of protein, as well as a higher content of flavonoids and total antioxidant potential of ozonated blueberries compared to non‐ozonated fruits.

CONCLUSION

The present study provides experimental evidence indicating that ozone treatment in proposed process conditions positively affects flavonoid metabolism in highbush blueberry fruit leading to the maintainance of the high quality of the fruit during storage. © 2021 Society of Chemical Industry.
An Analysis of Tracheostomy Complications in Pediatric Patients With Scoliosis
Authors: Appachi Swathi , Marcet‐Gonzalez Jessie , Brown Jennifer N. , Ongkasuwan Julina , Lambert Elton M.
Published: July 2021

Objectives/Hypothesis

To analyze tracheostomy‐related complications in pediatric patients with scoliosis.

Study Design

Retrospective chart review.

Methods

A retrospective chart review of all patients with tracheostomy and scoliosis was performed at a single institution. The charts were reviewed for variables including difficulties with tracheostomy tube changes, poor positioning of tube, abnormal appearance of trachea, and emergency room visits and admissions for complications. Decannulation rates were also identified.

Results

About 102 patients met inclusion criteria, 96 (94.1%) had scoliosis involving the thoracic spine, and 4 had scoliosis involving the cervical spine; 13 (12.8%) patients had documented poor positioning on tracheoscopy; 31 patients (30.3%) had at least one emergency room visit or admission for complications, such as accidental decannulation or bleeding from the tracheostomy; 19 (18.6%) patients required at least one tube change due to poor positioning, with 7 (6.9%) requiring multiple changes; 18 (17.7%) had reported difficulties with home tube changes. Custom length tubes were required in 9 patients (8.8%). The level of scoliosis was not associated with any of these complications. Abnormalities of the trachea, such as tortuosity, obstructive granulomas, or tracheomalacia, were seen in 35 patients (34.3%) on bronchoscopy. Scoliosis repair was performed in 18 patients (17.65%), of which two achieved decannulation. Ten patients (9.8%) overall were decannulated.

Conclusion

A portion of patients with scoliosis who are tracheostomy‐dependent have anatomical abnormalities of the trachea and poor positioning of the tracheostomy tube. Decannulation rates are also lower in this population compared to the literature. Further work is required to elucidate if scoliosis predisposes patients toward tracheostomy‐related complications.

Level of Evidence

4 Laryngoscope, 132:944–948, 2022
Long‐termwater color and flow trends in the Mississippi River Headwaters, 1944–2010
Authors: Germolus Noah P. , Brezonik Patrick L. , Hozalski Raymond M. , Finlay Jacques C.
Published: July 2021

Intensification of brown color in surface waters has been observed over several decades in many areas. We examined a 64‐yr daily record (1947–2010) of visual water color, a measure of chromophoric dissolved organic matter (CDOM), in the Mississippi River at Minneapolis, Minnesota. Although no monotonic trends in daily or mean annual color were evident, our analyses revealed trends in seasonal metrics, for example, mean winter color, on decadal scales related to changes in flow (hence climatic conditions). A pattern of high color (CDOM) in late spring and summer, corresponding with higher flow, was found across the period. Daily flow accounted for ~ 50% of the variance in color, and a lag of four days was found between peak responses of flow and color, supporting a CDOM source from wetlands in northern parts of the basin. The slope of the color‐flow relationship increased over the 64 yr, driven by increased CDOM flushing in late summer‐early fall. Based on trends in seasonally aggregated color and discharge, minimum and mean color and flow increased during winter over the 64 yr, potentially due to higher temperatures. Summer months did not show increases, but color became less variable. As a result, the color difference between summer and winter became smaller over the study period. During high flow events (ice‐out or high precipitation), some hysteretic color patterns were observed consistent with observations on other large rivers. Our results indicate that long‐term color (CDOM) trends in the Mississippi Headwaters reach are related to seasonally dominant changes in climatic conditions.