bluuebunny/crossref_metadata_2025 huggingface dataset:
Behaviour of 3,4‐Dihydroxy‐9,10‐Anthraquinone‐2‐Sulfonic Acid in Alkaline Medium: Towards a Long‐Cycling Aqueous Organic Redox Flow Battery
Authors: Guiheneuf Solène , Lê Aurore , Godet‐Bar Thibault , Chancelier Léa , Fontmorin Jean‐Marie , Floner Didier , Geneste Florence
Published: June 2021

The performance of a redox compound in redox flow batteries (RFB) highly depends on the electrolytic medium and operating conditions. It is exemplified in this work with the commercially available and relatively low‐cost dye 3,4‐dihydroxy‐9,10‐anthraquinone‐2‐sulfonic acid (ARS), which was used as negolyte in basic medium. At high pH, the ARS behavior revealed interesting features for RFB applications, such as a low half‐wave potential of −0.99 V (vs Ag/AgCl), negatively shifted by phenolate groups, and an improved solubility compared with acidic medium depending on the nature of the cations. For the highly soluble ARS potassium salt (ARSK), a maximum power density of 117 mW cm−2 and a demonstrated energy density of 20 Wh L−1 were obtained with K4[Fe(CN)6] as posolyte. The capacity slightly decreased during cycling, reaching 90 % after 325 cycles. A long cycling of ARS sodium salt (ARSNa) over 11 operating months was demonstrated in this work. A slow chemical degradation was highlighted giving rise to the formation of 3‐hydroxy‐9,10‐anthraquinone‐2‐sulfonic acid (HAQS) as the main degradation product due to hydrodeoxygenation reaction. Interestingly, this compound exhibited high performance in RFB and a good stability with a loss of capacity of 0.29 % per day.
Bipyridinium and Phenanthrolinium Dications for Metal‐Free Hydrodefluorination: Distinctive Carbon‐Based Reactivity
Authors: Burton Katherine I. , Elser Iris , Waked Alexander E. , Wagener Tobias , Andrews Ryan J. , Glorius Frank , Stephan Douglas W.
Published: June 2021

The development of novel Lewis acids derived from bipyridinium and phenanthrolinium dications is reported. Calculations of Hydride Ion Affinity (HIA) values indicate high carbon‐based Lewis acidity at the ortho and para positions. This arises in part from extensive LUMO delocalization across the aromatic backbones. Species [C10H6R2N2CH2CH2]2+ (R=H [1 a]2+, Me [1 f]2+, tBu [1 g]2+), and [C12H4R4N2CH2CH2]2+ (R=H [2 a]2+, Me [2 b]2+) were prepared and evaluated for use in the initiation of hydrodefluorination (HDF) catalysis. Compound [2 a]2+ proved highly effective towards generating catalytically active silylium cations via Lewis acid‐mediated hydride abstraction from silane. This enabled the HDF of a range of aryl‐ and alkyl‐ substituted sp3(C−F) bonds under mild conditions. The protocol was also adapted to effect the deuterodefluorination of cis‐2,4,6‐(CF3)3C6H9. The dications are shown to act as hydride acceptors with the isolation of neutral species C16H14N2 (3 a) and C16H10Me4N2 (3 b) and monocationic species [C14H13N2]+ ([4 a]+) and [C18H21N2]+ ([4 b]+). Experimental and computational data provide further support that the dications are initiators in the generation of silylium cations.
Mechanically Interlocked Chiral Self‐Templated [2]Catenanes from 2,6‐Bis(1,2,3‐triazol‐4‐yl)pyridine (btp) Ligands
Authors: McCarney Eoin P. , Lovitt June I. , Gunnlaugsson Thorfinnur
Published: June 2021

We report the efficient self‐templated formation of optically active 2,6‐bis(1,2,3‐triazol‐4‐yl)pyridine (btp) derived homocircuit [2]catenane enantiomers. This represents the first example of the enantiopure formation of chiral btp homocircuit [2]catenanes from starting materials consisting of a classical chiral element; X‐ray diffraction crystallography enabled the structural characterization of the [2]catenane. The self‐assembly reaction was monitored closely in solution facilitating the characterization of the pseudo‐rotaxane reaction intermediate prior to mechanically interlocking the pre‐organised system via ring‐closing metathesis.
Evolution of a Strategy for the Total Synthesis of (+)‐Cornexistin
Authors: Wildermuth Raphael E. , Steinborn Christian , Barber David M. , Mühlfenzl Kim S. , Kendlbacher Mario , Mayer Peter , Wurst Klaus , Magauer Thomas
Published: June 2021

Herein is given a full account of the evolution of the first total synthesis of (+)‐cornexistin. Initial efforts were based on masking the reactive maleic anhydride moiety as a 3,4‐substituted furan and on forming the nine‐membered carbocycle in an intramolecular Conia‐ene or Nozaki–Hiyama–Kishi (NHK) reaction. Those strategies suffered from low yields and were jeopardized by a late‐stage installation of the Z‐alkene, as well as the stereocenters along the eastern periphery. These issues were addressed by employing a chiral‐pool strategy that involved construction of the crucial stereocenters at C2, C3 and C8 at an early stage with installation of the maleic anhydride as late as possible. The successful approach featured an intermolecular NHK coupling to install the Z‐alkene, a syn‐Evans‐aldol reaction to forge the stereocenters along the eastern periphery, an intramolecular allylic alkylation to close the nine‐membered carbocycle, and a challenging stepwise hydrolysis of a β‐keto nitrile to furnish the maleic anhydride.
Calcium alginate‐regenerated spent bleaching earth composite beads for efficient removal of methylene blue
Authors: Aberkane Dihia , Meziti Chafika , Ihaddaden Soraya , Boukerroui Abdelhamid , Cagnon Benoît
Published: June 2021

This study aims to find an alternative method to the landfill of spent bleaching earth (SBE), which is a solid waste generated by the refining of edible oil that causes enormous ecological and environmental problems. This solid waste is clay loaded with impurities, colourants, and a large amount of oil entrained during the various stages of refining. In this study, the SBE was initially regenerated (RSBE) by thermal processing in a muffle furnace (temperature: 400°C, time: 1 h) followed by washing with an HCl solution. Then, the regenerated materials were encapsulated with calcium alginate (Alg) to form adsorbent composite beads (Alg‐RSBE). Different Alg/RSBE ratios were applied during materials elaboration, yielding beads denoted Alg‐RSBE 1/1 (1/1, w/w), Alg‐RSBE 1/2 (1/2, w/w), and Alg‐RSBE 1/3 (1/3, w/w), respectively. The Alg–RSBE composite beads were characterized by several methods (FTIR, SEM, EDX, TGA, pHPZC) and used as adsorbents of methylene blue (MB) in a fixed‐bed adsorption system. The adsorption of MB was studied at different experimental conditions such as contact time and initial MB concentration. The results showed that the kinetics of MB adsorption fitted to pseudo‐second‐order kinetics and the adsorption isotherm fitted to Langmuir isotherm. Among the three types of Alg‐RSBE composite beads, Alg‐RSBE 1/1 presents the highest MB adsorption capacity at 833.33 mg/g. Intraparticle and film diffusion equations were used to evaluate the kinetic data. Finally, the regeneration study showed that MB dye was successfully desorbed from Alg‐RSBE 1/1 with removal percentages from 93.32% to 88.15% after six cycles.
TDO2 overexpression correlates with poor prognosis, cancer stemness, and resistance to cetuximab in bladder cancer
Authors: Pham Quoc Thang , Taniyama Daiki , Akabane Shintaro , Harada Kenji , Babasaki Takashi , Sekino Yohei , Hayashi Tetsuraro , Sakamoto Naoya , Sentani Kazuhiro , Oue Naohide , Yasui Wataru
Published: June 2021

Background

Bladder cancer (BC) is the 10th most common cancer in the world. BC with muscle invasion results in a poor prognosis and is usually fatal. Cancer cell metabolism has an essential role in the development and progression of tumors. Expression of tryptophan 2,3‐dioxygenase (TDO2) is associated with tumor progression and worse survival in some other cancers. However, no studies have been performed to uncover the biofunctional roles of TDO2 in BC.

Aim

This study aim to investigate the clinicopathologic significance of TDO2 in BC.

Methods and results

TDO2 expression was evaluated by qRT‐PCR and immunohistochemistry in an integrated analysis with the Cancer Genome Atlas (TCGA) and other published datasets. TDO2 overexpression was significantly associated with T classification, N classification, and M classification, tumor stage, recurrence, and basal type, and with the expression of CD44 and aldehyde dehydrogenase 1 (ALDH1) in BC. High TDO2 expression correlated with poor outcome of BC patients. Using BC cell lines with knockdown and forced expression of TDO2, we found that TDO2 was involved in the growth, migration, and invasiveness of BC cells. Moreover, TDO2 was found to be crucial for spheroid formation in BC cells. Importantly, TDO2 promoted BC cells resistance to cetuximab through integration of the EGFR pathway.

Conclusion

Our results indicate that TDO2 might take an essential part in BC progression and could be a potential marker for targeted therapy in BC.
Group 12 Carbonates and their Binary Complexes with Nitrogen Bases and FH2Z Molecules (Z=P, As, Sb): Synergism in Forming Ternary Complexes
Authors: Liu Na , Li Qingzhong
Published: June 2021

MCO3(M=Zn, Cd, Hg) forms a spodium bond with nitrogen‐containing bases (HCN, NHCH2, NH3) and a pnicogen bond with FH2Z (Z=P, As, Sb). The spodium bond is very strong with the interaction energy ranging from −31 kcal/mol to −56 kcal/mol. Both NHCH2and NH3have an equal electrostatic potential on the N atom, but the corresponding interaction energy is differentiated by 1.5–4 kcal/mol due to the existence of spodium and hydrogen bonds in the complex with NHCH2as the electron donor. The spodium bond is weakest in the HCN complex, which is not consistent with the change of the binding distance. The spodium bond becomes stronger in the CdCO3<ZnCO3<HgCO3sequence although the positive electrostatic potential on the Hg atom is smallest. This is because the electrostatic interaction is dominant in the spodium‐bonded complexes of CdCO3and ZnCO3but the polarization interaction in that of HgCO3. The pnicogen bond is much weaker than the spodium bond and the former has a larger enhancement than the latter in the FH2Z⋅⋅⋅OCO2M⋅⋅⋅N‐base ternary complexes.
Label‐Free Protein Glycosylation Analysis Using NanoMonitor—An Ultrasensitive Electrochemical Biosensor
Authors: Ganguly Antra , Lin Kai‐Chun , Muthukumar Sriram , Nagaraj Vinay J. , Prasad Shalini
Published: June 2021

Glycans (oligosaccharide chains attached to glycoproteins) are a promising class of biomarkers, found in body fluids such as serum, saliva, urine, etc., that can be used for the diagnosis of disease conditions. Subtle changes in glycans resulting from altered glycosylation machinery have been reported during various diseases, including carcinogenesis. In this article, we detail protocols for the rapid, label‐free analysis of glycans using a previously developed highly sensitive and selective electrochemical impedance spectroscopy−based biosensing diagnostic platform called “NanoMonitor.” The glycosensor operation is based on the specific affinity capture of the target glycans on the sensor surface by glycan‐binding proteins known as lectins. This glycan‐lectin binding activity modulates the impedance of the electrical double layer at the buffer‐electrode interface. Protocols for the preparation of glycoprotein samples and glycosylation analysis using NanoMonitor and lectin‐based ELISA are described here. The data obtained using these protocols show that NanoMonitor is capable of distinguishing between glycoform variants of the glycoprotein fetuin and glycoproteins derived from cultured human pancreatic cancer cells with high sensitivity (orders of magnitude higher than lectin‐based ELISA) and selectivity. The results obtained indicate that NanoMonitor protocols can be further developed to enable use of NanoMonitor as a handheld electronic biosensor device for routine multiplexed detection of glycan biomarkers from clinical samples. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Preparing the NanoMonitor surface for glycan biosensing

Support Protocol: Synthesis of glycoform variants of fetuin

Basic Protocol 2: Performing Electrochemical Impedance Spectroscopy (EIS) for analyzing glycoprotein structures
Educational attainment for deaf people increases
Authors: Sutton Halley
Published: June 2021

While deaf people complete high school and college at a lower rate than hearing people, more than half of all deaf people complete “some college,” according to a report published by the National Deaf Center on Postsecondary Outcomes.
Professor retaliation and discrimination
Authors: Lyerly Eric
Published: June 2021

An overview of the key topics faced by disability services providers with citations to noteworthy cases, statutes, regulations, and additional sources.
The current state of uncertainty reporting in ecosystem studies: a systematic evaluation of peer‐reviewed literature
Authors: Yanai Ruth D. , Mann Thomas A. , Hong Sunghoon D. , Pu Ge , Zukswert Jenna M.
Published: June 2021

Transparency in reporting is essential to scientific progress. No report should be considered complete without a full account of uncertainties, including those due to natural variation and measurement and model error and those incurred by handling problematic data, such as outliers. We randomly selected 132 papers published in 2019 from a list of 100 scientific journals to characterize the current state of uncertainty reporting in ecosystem studies. Each paper was evaluated for the extent to which it reported measures of uncertainty in any of four topic areas common to ecosystem studies: vegetation, soils, precipitation, and surface water. We found that most papers reported a minority of the uncertainty sources we deemed relevant. Papers on surface water reported the highest fraction of uncertainty sources (averaging 47% ± 5%), followed by soils (45% ± 4%), vegetation (32% ± 4%), and precipitation (21% ± 8%). A greater fraction of relevant uncertainty sources were reported when the topics were the primary focus of the paper (44% ± 3%) than when they were not (32% ± 4%). Sampling error—the uncertainty in replicate measurements—was the source most commonly reported in studies of vegetation (84%), soil mass (56%), and surface water (76% of papers). The source of measurement error most often reported was chemical analysis, with 41% of papers on surface water and 75% of papers on precipitation reporting this source, if applicable. In contrast, only 1 of 12 papers reporting chemistry of vegetation provided information on analytical uncertainty. Fewer papers reported what methods were used for handling missing or unusable data and observations below detection limits, but it was difficult to judge whether these sources were relevant if they were not mentioned. Finally, we found that a minority of the papers made all (21%) or some (an additional 21%) of their data available in online repositories, after correcting for a failure rate of 13% of the links. Clearly, there is room for improving the completeness and transparency of scientific reporting in ecosystem studies.
Projected change in rangeland fractional component cover across the sagebrush biome under climate change through 2085
Authors: Rigge Matthew , Shi Hua , Postma Kory
Published: June 2021

Climate change over the past century has altered vegetation community composition and species distributions across rangelands in the western United States. The scale and magnitude of climatic influences are unknown. While many studies have projected the effects of climate change using several modeling approaches, none has evaluated the impacts to fractional component cover at a 30‐m resolution across the full sagebrush (Artemisiaspp.) biome. We used fractional component cover data for rangeland functional groups and weather data from the 1985 to 2018 reference period in conjunction with soils and topography data to develop empirical models describing the spatiotemporal variation in component cover. To investigate the ramifications of future change across the western United States, we extended models based on historical relationships over the reference period to model landscape effects based on future weather conditions from two emission scenarios and three time periods (2020s, 2050s, and 2080s). We tested both generalized additive models (GAMs) and regression tree models, finding that the former led to superior spatial and statistical results. Our results indicate more xeric vegetation across most of the study area, with an increasing dominance of non‐sagebrush shrubs, annual herbaceous cover, and bare ground over herbaceous and sagebrush cover in both the representative concentration pathway (RCP) 4.5 and 8.5 scenarios. In general, both scenarios yielded similar results, but RCP 8.5 tended to be more extreme, with greater change relative to the reference period. Results demonstrate that in cool sites some degree of warming to growing season maximum temperature or nongrowing season minimum temperature could be beneficial to sagebrush and shrub growth. However, warming nongrowing season maximum temperature was beneficial to shrub, but not to sagebrush growth. Our results inform rangeland managers of potential future vegetation composition, cover, and species distributions, which could improve prioritization of conservation and restoration efforts.
Importance of low‐relief nursery habitat for reef fishes
Authors: Dance Michael A. , Rooker Jay R. , Kline Richard J. , Quigg Antonietta , Stunz Gregory R. , Wells R. J. David , Lara Kirsten , Lee Jessica , Suarez Bobbie
Published: June 2021

Coastal restoration projects to mitigate environmental impacts have increased global demand for sand resources. Unfortunately, these resources are often extracted from sand/shell banks on the inner continental shelf, resulting in significant alteration or loss of low‐relief reefs in coastal oceans. Experimental reefs (oyster shell, limestone rubble, composite) were deployed in the western Gulf of Mexico to assess their potential value as nurseries for newly settled reef fishes. Occurrence, abundance, and species richness of juvenile fishes were significantly higher on all three types of low‐relief reefs compared with unconsolidated sediment. Moreover, reefs served as nursery habitat for a range of reef fish taxa (angelfishes, grunts, sea basses, snappers, and triggerfishes). Red snapper (Lutjanus campechanus) was the dominant species present on all experimental reefs (100% occurrence), and mean density of this species was markedly higher on each of the three low‐relief reefs (>40.0 individuals/reef) relative to comparable areas over unconsolidated sediment (0.2 individuals). Our results suggest creation or restoration of structurally complex habitat on the inner shelf has the potential to markedly increase early life survival and expedite the recovery of exploited reef fish populations, and therefore may represent a critical conservation tool for increasing recruitment and maintaining reef fish diversity.
Shifting macroecological patterns and static theory failure in a stressed alpine plant community
Authors: Franzman Juliette , Brush Micah , Umemura Kaito , Ray Courtenay , Blonder Benjamin , Harte John
Published: June 2021

Accumulating evidence suggests that ecological communities undergoing change in response to either anthropogenic or natural disturbances exhibit macroecological patterns that differ from those observed in similar types of communities in relatively undisturbed sites. In contrast to such cross‐site comparisons, however, there are few empirical studies of shifts over time in the shapes of macroecological patterns. Here, we provide a dramatic example of a plant community in which the species–area relationship and the species‐abundance distribution change markedly over a period of six years. These patterns increasingly deviate from the predictions of the maximum entropy theory of ecology (METE), which successfully predicts macroecological patterns in relatively static systems. The error in the species–area relationship prediction additionally correlates over time with increased stress measured as mortality minus recruitment, providing a link between demography and the failure of macroecological theory. Information on the dynamic state of an ecosystem inferred from snapshot measurements of macroecological community structure can potentially assist in identifying causes and consequences of disturbance and extending the domain of current theories and models to disturbed ecosystems.
Big bees spread disease: body size mediates transmission of a bumble bee pathogen
Authors: Van Wyk Jennifer I. , Amponsah Eugene R. , Ng Wee Hao , Adler Lynn S.
Published: June 2021

Trait variation can have important consequences for the outcomes of species interactions. Even though some traits vary as much within species as across related species, models and empirical studies typically do not consider the role of intraspecific trait variation for processes such as disease transmission. For example, many pollinator species are in decline because of a variety of stressors including pathogens, but the role of intraspecific trait variation in mediating disease dynamics is rarely considered. For example, pollinator body size could affect pathogen transmission via differences in resistance, foraging behavior and physiology. We tested effects of body size on pollinator pathogen transmission using the common eastern bumble beeBombus impatiensin field tents, introducing an infected “donor” microcolony of large or small workers with an uninfected average‐sized “recipient” microcolony and allowing bees to forage for 9–16 d. Small donor bees had nearly 50% higher infection intensity (cells/0.02  μL) than large donor bees, but large donor bees were twice as likely to transmitCrithidia bombito recipient bees. Both behavioral and physiological mechanisms may underlie this apparent paradox. Compared to small bees, large bees foraged more and produced more feces; simulations showed that foraging and defecation rates together had stronger effects on transmission than did donor infection intensity. Thus, effects of bee size on contact rates and pathogen supply may play significant roles in disease transmission, demonstrating the multifaceted impacts of traits on transmission dynamics.
The impact of DNA extract homogenization and replication on marine sediment metabarcoding diversity and heterogeneity
Authors: Hestetun Jon Thomassen , Lanzén Anders , Skaar Katrine Sandnes , Dahlgren Thomas G.
Published: June 2021

Metabarcoding of environmental DNA (eDNA) is an attractive complement to morphological methods for surveys and routine monitoring of marine sediment benthic communities. However, metabarcoding and other genetic techniques are heavily affected by choices made during sampling, processing, and analysis. Here, we investigated the effect of different eDNA extraction protocols on observed alpha‐ and beta diversity of replicates from the same grab. Specifically, we compared (A) homogenization intensity during sediment DNA extraction, (B) extraction replicates vs larger sediment extraction volume, and (C) pre‐ and post‐PCR extract pooling. Using the 18S V1‐V2 region marker, we show that a Precellys homogenizer protocol during DNA extraction can significantly improve sediment metabarcoding results in terms of captured diversity and inter‐replicate homogeneity compared to vortexing only. This effect superseded that of increased sediment extract volume. Pre‐PCR pooling of DNA extraction replicates increased observed rarefied richness compared to data from single extracts only, but not to the extent of sample extract replicates amplified individually before pooling. We argue that this discrepancy was due to a reduction both in recovered sample diversity, but also the number of PCR artifacts and PCR drift. Our results demonstrate that extraction replicates of smaller sediment volumes, in combination with moderate Precellys homogenization and pre‐PCR pooling, are a cost‐effective way to increase the amount of organism diversity that is recovered from sediment eDNA metabarcoding samples.
Tofacitinib therapy intercepts macrophage metabolic reprogramming instigated by SARS‐CoV‐2 Spike protein
Authors: Palasiewicz Karol , Umar Sadiq , Romay Bianca , Zomorrodi Ryan K. , Shahrara Shiva
Published: June 2021

The molecular mechanism of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Spike protein was characterized to identify novel therapies. The impact of tofacitinib, IL‐6R Ab, or TNFi therapy was determined on Spike protein or LPS/IFN‐γ‐induced signaling, inflammation, and metabolic reprogramming in MΦs and/or rheumatoid arthritis (RA) fibroblast‐like synoviocyte (FLS). ACE2 frequency was markedly expanded in MΦs compared to T cells and RA FLS. Tofacitinib suppresses Spike protein potentiated STAT1 signaling, whereas this function was unchanged by TNFi. Tofacitinib impairs IL‐6/IFN/LPS‐induced STAT1 and STAT3 phosphorylation in RA MΦs and FLS. Interestingly, tofacitinib had a broader inhibitory effect on the monokines, glycolytic regulators, or oxidative metabolites compared to IL‐6R Ab and TNFi in Spike‐protein‐activated MΦs. In contrast, all three therapies disrupted IFN‐α and IFN‐β secretion in response to Spike protein; nonetheless, the IFN‐γ was only curtailed by tofacitinib or IL‐6R Ab. While tofacitinib counteracted MΦ metabolic rewiring instigated by Spike protein, it was inconsequential on the glycolysis expansion mediated via HK2 and/or LDHA in the activated RA MΦ and FLS. Nevertheless, the potentiated inflammatory response and the diminished oxidative phosphorylation modulated by Spike protein and/or LPS/IFN‐γ stimulation in MΦs or RA FLS were reversed by tofacitinib. In conclusion, tofacitinib suppresses MΦ inflammation and immunometabolism triggered by Spike protein and may provide a promising strategy for COVID‐19 patients.
Synthesis and Magnetic Properties of Two‐Step‐Coordination Schiff Base Clusters
Authors: Peters Laurens C. J. M. , Engelkamp Hans , Zeitler Uli , Christianen Peter C. M. , Tinnemans Paul , Maan Jan‐Kees , Rowan Alan E.
Published: June 2021

A new family of paramagnetic coordination compounds based on a diimine‐pyridine pincer ligand has been prepared, using a two‐step synthetic approach. The sequential introduction of identical or different transition metals (Co, Mn, Ni, Zn) afforded mono‐, di‐, tri‐ and tetranuclear clusters, whose crystal structure has been determined. Magnetic studies reveal that the metals within the trinuclear manganese cluster engage in a small ferromagnetic exchange interaction (J=0.15 K). These studies enable the design of new clusters with specific magnetic properties.
Asymmetric Total Synthesis of (−)‐Dehydrocostus Lactone by Domino Metathesis
Authors: Kaden Felix , Nowotni Susanne , Höfner Franziska , Lorenz Melanie , Barthel André , Jäger Anne , Hennersdorf Felix , Weigand Jan J. , Metz Peter
Published: June 2021

An efficient total synthesis of the sesquiterpenoid (−)‐dehydrocostus lactone is reported. Our earlier approach by a domino enediyne metathesis was extended by a domino dienyne metathesis strategy to give access to suitably functionalized hydroazulene cores. Highly stereoselective asymmetric anti aldol reactions provided the enantiopure substrates for this key step of our synthesis. Multiple hydroboration/oxidation of the resulting hydroazulenes set up three out of four stereogenic centers in a single step. First, oxidation to give a diketo‐γ‐lactone enabled an enantioselective formal synthesis of the target guaianolide. Subsequently, the final steps of this approach were improved by using a double carbonyl olefination at the stage of a masked γ‐butyrolactone, which completed the synthesis in a much more efficient way.
Large device to device communication network including airborne drones for emergency scenarios
Authors: Grinewitschus Lukas , Almujahed Hamza , Fresia Maria , Mueck Markus , Bruck Guido , Jung Peter
Published: June 2021

In the case of emergency scenarios communication infrastructure might be destroyed, impairing communication abilities in the disaster area. In such situation device‐to‐device (D2D) communication networking plays an essential role to overcome the communication loss. To provide a reliable communication network, D2D devices are combined with airborne drones. The D2D devices provide a relay service while being able to transmit their own data. The airborne drones offer additional relay functionality and provide considerably reduced latency compared with D2D communication networks without any airborne drones. In this article, we will illustrate a large dynamic communication network (LDCN) and demonstrate its feasibility for even more than 64 000 D2D communication devices in the case of realistic channel conditions including path loss and fading. It will be shown that the illustrated LDCN is truly infrastructure‐less, that is, no infrastructure or backbone or base station functionality need to be reinstalled. Therefore, the airborne drones do not take over any coordination services. The illustrated LDCN has a simple packet switching architecture and since all communication is localized it is robust and fully flexible. In addition, no specific radio interface or preferred multiple access scheme such as code division multiple access or time division multiple access are required.
Explicit calculation for the pressure Poisson equation to simulate incompressible fluid flows in a mesh‐free method
Authors: Xu Tibing
Published: June 2021

In this study, an equation is derived to explicitly solve the pressure Poisson equation (PPE) in the moving particle semiimplicit method. In the derivation, the PPE is discretized by an improved Laplacian model and the incompressible condition is satisfied by establishing a direct relationship between pressure and the known flow information. An improved gradient model is adopted in the method while a repulsive force is used to handle particle clustering. To validate the method, a hydrostatic problem, the impact of two rectangular fluid patches and dam‐breaking flows are simulated. The numerical results are compared with analytical solutions and experimental measurements in terms of free surface, pressure, and velocity. Good agreements in the comparisons are achieved, showing that the method can calculate smooth pressure field and accurate pressure and velocity distributions.
The dynamics of cross‐boundary fire—Financial contagion between the oil and stock markets
Authors: Wang Haiying , Yuan Ying , Wang Tianyang
Published: June 2021

Motivated by the complex dynamics between the oil and stock markets, this study develops a dynamic Markov regime switching‐copula‐extreme value theory model to quantitatively investigate financial contagion and its characteristics between these two markets. The proposed model is applied to daily returns on crude oil prices and the stock markets in the United States and China over six major extreme downside risk events. We find that financial contagion is shorter, stronger, and more susceptible to extreme downside shocks in the United States than in China. In addition, the COVID‐19 crisis shows the largest financial contagion compared with previous crises.
Data‐driven beamforming technique to attenuate ballistocardiogram artefacts in electroencephalography–functional magnetic resonance imaging without detecting cardiac pulses in electrocardiography recordings
Authors: Uji Makoto , Cross Nathan , Pomares Florence B. , Perrault Aurore A. , Jegou Aude , Nguyen Alex , Aydin Umit , Lina Jean‐Marc , Dang‐Vu Thien Thanh , Grova Christophe
Published: June 2021

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is a very promising non‐invasive neuroimaging technique. However, EEG data obtained from the simultaneous EEG–fMRI are strongly influenced by MRI‐related artefacts, namely gradient artefacts (GA) and ballistocardiogram (BCG) artefacts. When compared to the GA correction, the BCG correction is more challenging to remove due to its inherent variabilities and dynamic changes over time. The standard BCG correction (i.e., average artefact subtraction [AAS]), require detecting cardiac pulses from simultaneous electrocardiography (ECG) recording. However, ECG signals are also distorted and will become problematic for detecting reliable cardiac peaks. In this study, we focused on a beamforming spatial filtering technique to attenuate all unwanted source activities outside of the brain. Specifically, we applied the beamforming technique to attenuate the BCG artefact in EEG–fMRI, and also to recover meaningful task‐based neural signals during an attentional network task (ANT) which required participants to identify visual cues and respond accurately. We analysed EEG–fMRI data in 20 healthy participants during the ANT, and compared four different BCG corrections (non‐BCG corrected, AAS BCG corrected, beamforming + AAS BCG corrected, beamforming BCG corrected). We demonstrated that the beamforming approach did not only significantly reduce the BCG artefacts, but also significantly recovered the expected task‐based brain activity when compared to the standard AAS correction. This data‐driven beamforming technique appears promising especially for longer data acquisition of sleep and resting EEG–fMRI. Our findings extend previous work regarding the recovery of meaningful EEG signals by an optimized suppression of MRI‐related artefacts.
HybraPD atlas: Towards precise subcortical nuclei segmentation using multimodality medical images in patients with Parkinson disease
Authors: Yu Boliang , Li Ling , Guan Xiaojun , Xu Xiaojun , Liu Xueling , Yang Qing , Wei Hongjiang , Zuo Chuantao , Zhang Yuyao
Published: June 2021

Human brain atlases are essential for research and surgical treatment of Parkinson's disease (PD). For example, deep brain stimulation for PD often requires human brain atlases for brain structure identification. However, few atlases can provide disease‐specific subcortical structures for PD, and most of them are based on T1w and T2w images. In this work, we construct a HybraPD atlas using fused quantitative susceptibility mapping (QSM) and T1w images from 87 patients with PD. The constructed HybraPD atlas provides a series of templates, that is, T1w, GRE magnitude, QSM, R2*, and brain tissue probabilistic maps. Then, we manually delineate a parcellation map with 12 bilateral subcortical nuclei, which are highly related to PD pathology, such as sub‐regions in globus pallidus and substantia nigra. Furthermore, we build a whole‐brain parcellation map by combining existing cortical parcellation and white‐matter segmentation with the proposed subcortical nuclei map. Considering the multimodality of the HybraPD atlas, the segmentation accuracy of each nucleus is evaluated using T1w and QSM templates, respectively. The results show that the HybraPD atlas provides more accurate segmentation than existing atlases. Moreover, we analyze the metabolic difference in subcortical nuclei between PD patients and healthy control subjects by applying the HybraPD atlas to calculate uptake values of contrast agents on positron emission tomography (PET) images. The atlas‐based analysis generates accurate disease‐related brain nuclei segmentation on PET images. The newly developed HybraPD atlas could serve as an efficient template to study brain pathological alterations in subcortical regions for PD research.
Transcriptomics Identify Thrombospondin‐2 as a Biomarker for NASH and Advanced Liver Fibrosis
Authors: Kozumi Kazuhiro , Kodama Takahiro , Murai Hiroki , Sakane Sadatsugu , Govaere Olivier , Cockell Simon , Motooka Daisuke , Kakita Naruyasu , Yamada Yukinori , Kondo Yasuteru , Tahata Yuki , Yamada Ryoko , Hikita Hayato , Sakamori Ryotaro , Kamada Yoshihiro , Daly Ann K. , Anstee Quentin M. , Tatsumi Tomohide , Morii Eiichi , Takehara Tetsuo
Published: June 2021

Background and Aims

NAFLD is the most common liver disease worldwide. NASH, the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes. We searched for their noninvasive biomarkers.

Approach and Results

Global RNA sequencing of liver tissue from 98 patients with biopsy‐proven NAFLD was performed. Unsupervised hierarchical clustering well distinguished NASH from nonalcoholic fatty liver (NAFL), and patients with NASH exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified proteins up‐regulated in NASH and/or advanced fibrosis (stage F3‐F4), including matricellular glycoprotein thrombospondin‐2 (TSP‐2), encoded by the thrombospondin 2 (THBS2) gene. The intrahepatic THBS2 expression level showed the highest areas under the receiver operating characteristic curves (AUROCs) of 0.915 and 0.957 for diagnosing NASH and advanced fibrosis, respectively. THBS2 positively correlated with inflammation and ballooning according to NAFLD activity score, serum aspartate aminotransferase and hyaluronic acid (HA) levels, and NAFLD Fibrosis Score (NFS). THBS2 was associated with extracellular matrix and collagen biosynthesis, platelet activation, caspase‐mediated cleavage of cytoskeletal proteins, and immune cell infiltration. Serum TSP‐2 expression was measured in 213 patients with biopsy‐proven NAFLD, was significantly higher in NASH than in NAFL, and increased parallel to fibrosis stage. The AUROCs for predicting NASH and advanced fibrosis were 0.776 and 0.856, respectively, which were comparable to Fibrosis‐4 index, serum HA level, and NFS in advanced fibrosis diagnosis. Serum TSP‐2 level and platelet count were independent predictors of NASH and advanced fibrosis. Serum TSP‐2 levels could stratify patients with NAFLD according to the risk of hepatic complications, including liver cancer and decompensated cirrhotic events.

Conclusions

TSP‐2 may be a useful biomarker for NASH and advanced fibrosis diagnosis in patients with NAFLD.
Disrupting the medial prefrontal cortex with designer receptors exclusively activated by designer drug alters hippocampal sharp‐wave ripples and their associated cognitive processes
Authors: Schmidt Brandy , Redish A. David
Published: June 2021

The hippocampus and medial prefrontal cortex (mPFC) interact during a myriad of cognitive processes including decision‐making and long‐term memory consolidation. Exactly how the mPFC and hippocampus interact during goal‐directed decision‐making remains to be fully elucidated. During periods of rest, bursts of high‐frequency oscillations, termed sharp‐wave ripple (SWR), appear in the local field potential. Impairing SWRs on the maze or during post‐learning rest can interfere with memory‐guided decision‐making and memory consolidation. We hypothesize that the hippocampus and mPFC bidirectionally interact during SWRs to support memory consolidation and decision‐making. Rats were trained on the neuroeconomic spatial decision‐making task, Restaurant Row, to make serial stay‐skip decisions where the amount of effort (delay to reward) varied upon entry to each restaurant. Hippocampal cells and SWRs were recorded in rats with the mPFC transduced with inhibitory DREADDs. We found that disrupting the mPFC impaired consolidating SWRs in the hippocampus. Hippocampal SWR rates depended on the internalized value of the reward (derived from individual flavor preferences), a parameter important in decision‐making, and disrupting the mPFC changed this relationship. Additionally, we found a dissociation between SWRs that occurred while rats were on the maze dependent upon whether those SWRs occurred while the rat was anticipating food reward or during post‐reward consumption.
Optimizing CAR T cell therapy in lymphoma
Authors: Qualls David , Salles Gilles
Published: June 2021

Chimeric antigen receptor (CAR) T cell therapy has significantly improved the outlook for patients with certain types of poor‐risk lymphoma. Despite these advances, a majority of patients undergoing CAR T therapy will suffer progression or relapse of disease, and toxicity remains a concern. Additionally, the patients and disease subtypes that are most likely to benefit from CAR T have yet to be fully defined. Many ongoing trials are exploring novel CAR T approaches to address these concerns. In this review, we highlight some of the primary strategies and relevant studies aimed at improving the utility of CAR T therapy in lymphoma.
Upfront identification of high‐risk follicular lymphoma
Authors: Casulo Carla
Published: June 2021

Follicular lymphoma (FL) is a common disease with clinically indolent behavior, and a long natural history for the majority of patients. Despite excellent therapeutic strategies currently available for FL, approximately 10%–20% of patients will experience early disease progression, defined as occurring within two years of diagnosis. These patients have poor outcomes, with overall survival at 5 years ranging between 37% and 50%. Much of the biology driving early progression and inferior survival is attributed to early transformation events; however, transformation alone does not account for all the observed clinical heterogeneity and survival differences among patients. Several clinical, genetic, and molecular alterations in FL have been discovered that help define subsets of patients at risk for multiply relapses and refractory disease, and are slowly making their way into risk calculators to be used in daily practice. Additionally, the role of functional imaging with PET scan, as well as circulating and cell free tumor DNA are being evaluated as tools to define high‐risk subsets of patients with FL. This review seeks to provide an over view of current and evolving biomarkers that define high‐risk FL at diagnosis. The goal is for these tools to assist clinicians in integrating these rapidly evolving prognosis models into clinical practice, in the hopes of risk‐stratifying treatments and improving outcomes for patients.
High‐risk follicular lymphoma: Treatment options
Authors: Kahl Brad
Published: June 2021

Follicular lymphoma (FL) is the most common indolent non‐Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab. Randomized clinical trials have demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Maintenance rituximab strategies can improve progression‐free survival (PFS). Obinutuzumab was superior to rituximab for PFS in the GALLIUM study, although the benefit was small and required more drug. Chemotherapy platforms have changed in the past decade, as bendamustine combined with rituximab has become commonly utilized frontline strategy in North America and parts of Europe, although there is certainly no one standard treatment. However, several unmet needs remain, including a better ability to identify high‐risk patients at diagnosis, the development of predictive biomarkers for targeted agents, the development of novel combinations, and strategies to reduce the risk of transformation. A multitude of novel therapies are under investigation in both the frontline and relapsed/refractory settings. It will be critical to identify the most appropriate populations for new agents and to develop validated surrogate endpoints, so that novel agents can be tested (and adopted, if appropriate) efficiently.
Recognizing but not harming. Borderline B‐cell lymphoid proliferations
Authors: Quintanilla‐Martinez Leticia
Published: June 2021

In the last years several borderline B‐cell lymphoid proliferations have been recognized that lie at the interface between benign and malignant. These lesions can be divided in two groups; those considered precursor lesions of well recognized lymphoid malignancies and the group of indolent lymphomas with limited potential for progression. Precursor lesions are monoclonal and share many genetic features of their malignant counterpart. The first recognized precursor lesion was monoclonal gammopathy of undetermined significance. Thereafter, the widespread use of immunohistochemistry, fluorescence‐activated cell sorting analysis and molecular techniques in lymphoid samples led to the recognition of other precursor lesions such as monoclonal B‐cell lymphocytosis, in situ follicular neoplasia and in situ mantle cell neoplasia. The second group of disorders comprises monoclonal lymphoid proliferations with limited malignant potential without a counterpart among the currently recognized lymphoma entities; these include pediatric‐type follicular lymphoma, pediatric nodal marginal zone lymphoma, and duodenal‐type follicular lymphoma. Despite their clonal nature, a conservative treatment has been shown to be sufficient in most cases. The diagnostic criteria of precursor/indolent B‐cell proliferations, recent advances in the understanding of progression and lymphomagenesis and current recommendations for treatment will be discussed. In order to avoid unnecessary and potentially harmful therapy, these lesions need to be recognized and diagnosed correctly.
Vulnerabilities in the tumor and microenvironment in follicular lymphoma
Authors: Araujo‐Ayala Ferran , Pérez‐Galán Patricia , Campo Elias
Published: June 2021

Follicular lymphoma (FL) is a paradigm of tumors that require the interaction between tumor and microenvironment cells to foster their development from initial steps to progression. Recent large‐scale genome studies have uncovered multiple genetic alterations of FL that influence the microenvironment in two main directions, promoting tumor cell survival and proliferation and facilitating their evasion from immune antitumor signals. Understanding the crosstalk between tumor B‐cells and the microenvironment will facilitate the identification of vulnerabilities that may offer novel targets for treatment of the patients. This review highlights recent findings showing the effect of common genetic mutations modulating the cell composition of the tumor microenvironment and the novel therapeutic perspectives to target these interactions.
Impact of variation of nanoparticle shape on free convective MHD water‐based flow of Hamilton–Crosser model radiative nanofluids over a permeable surface
Authors: Ratha P. K. , Tripathy R. S. , Mishra S. R.
Published: June 2021

The present analysis explores the impact of shape of the nanoparticles on the conducting nanofluids past a porous surface. The electrically conducting fluid possesses enhanced physical properties due to the thermal buoyancy, and the radiative heat energy enhances the thermal properties of the water‐based nanofluid. The suitable choice of a nanoparticle, that is, considering the metal particle like copper (Cu) and oxide particle such as TiO2 in conjunction with the Hamilton–Crosser model thermal conductivity, augments the heat transfer properties. The appropriate transformation of similarity variable and the stream function helps to convert the leading partial differential equations to nonlinear ordinary differential equations (ODEs). Furthermore, these distorted ODEs are handled by using numerical technique such as Runge–Kutta–Fehlberg along with the shooting technique. The graphical presentation of the profiles of flow phenomena due to the interaction of relevant parameters is deployed for the physical significance, and the comparison of the present investigation shows a good agreement with the earlier results. However, the major outcomes are as follows; backflow occurs near the surface region due to the impermeable surface also increasing shape of the nanoparticle decelerates the fluid temperature and it is useful by considering the spherical shaped nanoparticles for the enhanced heat transfer.