bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of protein N-terminal peptides by charge-mediated position-selective enrichment using strong cation exchange chromatography
Authors: Chang Chih-Hsiang , Chang Hsin-Yi , Rappsilber Juri , Ishihama Yasushi
Published: June 2020

We developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N-termini, and then the N-terminal peptides are separated from the internal peptides by means of CHArge-Mediated Position-selective (CHAMP) enrichment using strong cation exchange (SCX) chromatography. This CHAMP-SCX approach was applied to 20 μg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1,550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N-termini registered in the Swiss-Prot database. Since this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N-termini, including proteoforms with neo-N-termini.
Negative interplay between biofilm formation and competence in the environmental strains ofBacillus subtilis
Authors: She Qianxuan , Hunter Evan , Qin Yuxuan , Nicolau Samantha , Zalis Eliza A. , Wang Hongkai , Chen Yun , Chai Yunrong
Published: June 2020

Environmental strains of the soil bacteriumBacillus subtilishave valuable applications in agriculture, industry, and biotechnology. They are capable of forming robust biofilms and demonstrate excellent biological control activities in plant protection. However, environmental strains are genetically less accessible, a sharp contrast to the laboratory strains well known for their natural competence and a limitation toward their application. In this study, we observed that robust biofilm formation of the environmental strains greatly reduces the rate of competent cells within the biofilm. By using the model strain 3610, we reveal a cross-pathway regulation that allows biofilm matrix producers and competence-developing cells to undergo mutually exclusive cell differentiation. We show that the competence activator ComK represses the key biofilm regulatory genesinIby directly binding to thesinIpromoter, thus blocking competent cells from simultaneously becoming matrix producers. In parallel, the biofilm activator SlrR represses competence through three distinct mechanisms, involving both genetic regulation and cell morphological changes. We discuss potential implications of limiting competence in a bacterial biofilm.

Importance

The soil bacteriumBacillus subtilisis capable of forming robust biofilms, a multicellular community important for its survival in the environment.B. subtilisalso exhibits natural competence, the ability of cells to acquire genetic materials directly from the environment. By investigating competence developmentin situduringB. subtilisbiofilm formation, we reveal that robust biofilm formation, an important feature of the environmental strains ofB. subtilis, often greatly reduces the rate of competent cells within the biofilm. We characterize a cross-pathway regulation that allows cells associated with these two developmental events to undergo mutually exclusive cell differentiation during biofilm formation. Finally, we discuss potential biological implications of limiting competence in a bacterial biofilm.
A CRISPRi-dCas9 system for archaea and its use to examine gene function during nitrogen fixation byMethanosarcina acetivorans
Authors: Dhamad Ahmed E. , Lessner Daniel J.
Published: June 2020

CRISPR-based systems are emerging as the premier method to manipulate many cellular processes. In this study, a simple and efficient CRISPR interference (CRISPRi) system for targeted gene repression in archaea was developed. TheMethanosarcina acetivoransCRISPR-Cas9 system was repurposed by replacing Cas9 with the catalytically dead Cas9 (dCas9) to generate a CRISPRi-dCas9 system for targeted gene repression. To test the utility of the system, genes involved in nitrogen (N2) fixation were targeted for dCas9-mediated repression. First, thenifoperon (nifHI1I2DKEN) that encodes molybdenum nitrogenase was targeted by separate guide RNAs (gRNA), one targeting the promoter and the othernifD. Remarkably, growth ofM. acetivoranswith N2was abolished by dCas9-mediated repression of thenifoperon with each gRNA. The abundance ofniftranscripts was >90% reduced in both strains expressing the gRNAs, and NifD was not detected in cell lysate. Next, we targeted NifB, which is required for nitrogenase cofactor biogenesis. Expression of a gRNA targeting the coding sequence of NifB decreasednifBtranscript abundance >85% and impaired but did not abolish growth ofM. acetivoranswith N2. Finally, to ascertain the ability to study gene regulation using CRISPRi-dCas9,nrpR1encoding a subunit of the repressor of thenifoperon was targeted. ThenrpR1repression strain grew normally with N2but had increasednifoperon transcript abundance consistent with a NrpR1 as repressor. These results highlight the utility of the system, whereby a single gRNA when expressed with dCas9 can block transcription of targeted genes and operons inM. acetivorans.

IMPORTANCE

Genetic tools are needed to understand and manipulate the biology of archaea, which serve critical roles in the biosphere. Methanogenic archaea (methanogens) are essential for the biological production of methane, an intermediate in the global carbon cycle, an important greenhouse gas and a biofuel. The CRISPRi-dCas9 system in the model methanogenM. acetivoransis the first Cas9-based CRISPR interference system in archaea. Results demonstrate that the system is remarkably efficient in targeted gene repression and provide new insight into nitrogen fixation by methanogens, the only archaea with nitrogenase. Overall, the CRISPRi-dCas9 system provides a simple, yet powerful, genetic tool to control the expression of target genes and operons in methanogens.
PQS-Induced Outer Membrane Vesicles Enhance Biofilm Dispersion inPseudomonas aeruginosa
Authors: Cooke Adam C. , Florez Catalina , Dunshee Elise B. , Lieber Avery D. , Terry Michelle L. , Light Caitlin J. , Schertzer Jeffrey W.
Published: June 2020

Bacterial biofilms are major contributors to chronic infections in humans. Because they are recalcitrant to conventional therapy, they present a particularly difficult treatment challenge. Identifying factors involved in biofilm development can help uncover novel targets and guide the development of anti-biofilm strategies.Pseudomonas aeruginosacauses surgical site, burn wound, and hospital acquired infections, and is also associated with aggressive biofilm formation in the lungs of cystic fibrosis patients. A potent but poorly understood contributor toP. aeruginosavirulence is the ability to produce outer membrane vesicles (OMVs). OMV trafficking has been associated with cell-to-cell communication, virulence factor delivery, and the transfer of antibiotic resistance genes. Because OMVs have almost exclusively been studied using planktonic cultures, little is known about their biogenesis and function in biofilms. Our group has shown that the Pseudomonas Quinolone Signal (PQS) induces OMV formation inP. aeruginosa, and in other species, through a biophysical mechanism that is also active in biofilms. Here, we demonstrate that PQS-induced OMV production is highly dynamic during biofilm development. Interestingly, PQS and OMV synthesis are significantly elevated during dispersion, compared to attachment and maturation stages. PQS biosynthetic and receptor mutant biofilms were significantly impaired in their ability to disperse, but this phenotype could be rescued by genetic complementation or exogenous addition of PQS. Finally, we show that purified OMVs can actively degrade extracellular protein, lipid, and DNA. We therefore propose that enhanced production of PQS-induced OMVs during biofilm dispersion facilitates cell escape by coordinating the controlled degradation of biofilm matrix components.

Importance

Treatments that manipulate biofilm dispersion hold the potential to convert chronic drug-tolerant biofilm infections from protected sessile communities into released populations that are orders-of-magnitude more susceptible to antimicrobial treatment. However, dispersed cells often exhibit increased acute virulence and dissemination phenotypes. A thorough understanding of the dispersion process is therefore critical before this promising strategy can be effectively employed. PQS has been implicated in early biofilm development, but we hypothesized that its function as an OMV inducer may contribute at multiple stages. Here, we demonstrate that PQS and OMVs are differentially produced duringPseudomonas aeruginosabiofilm development and that effective biofilm dispersion is dependent on production of PQS-induced OMVs, which likely act as delivery vehicles for matrix degrading enzymes. These findings lay the groundwork for understanding the roles of OMVs in biofilm development and suggest a model to explain the controlled matrix degradation that accompanies biofilm dispersion in many species.
What has been the impact of Covid-19 on Safety Culture? A case study from a large metropolitan teaching hospital
Authors: Denning Max , Goh Ee Teng , Scott Alasdair , Martin Guy , Markar Sheraz , Flott Kelsey , Mason Sam , Przybylowicz Jan , Almonte Melanie , Clarke Jonathan , Winter-Beatty Jasmine , Chidambaram Swathikan , Yalamanchili Seema , Tan Benjamin Yong-Qiang , Kanneganti Abhiram , Sounderajah Viknesh , Wells Mary , Purkayastha Sanjay , Kinross James
Published: June 2020

Introduction

Covid-19 has placed an unprecedented demand on healthcare systems worldwide. A positive safety culture is associated with improved patient safety and in turn patient outcomes. To date, no study has evaluated the impact of Covid-19 on safety culture.

Methods

The Safety Attitudes Questionnaire (SAQ) was used to investigate safety culture at a large UK teaching hospital during Covid-19. Findings were compared with baseline data from 2017. Incident reporting from the year preceding the pandemic was also examined.

Results

Significant increased were seen in SAQ scores of doctors and ‘other clinical staff’, there was no change in the nursing group. During Covid-19, on univariate regression analysis, female gender, age 40-49 years, non-white ethnicity, and nursing job role were all associated with lower SAQ scores. Training and support for redeployment were associated with higher SAQ scores. On multivariate analysis, non-disclosed gender (−0.13), non-disclosed ethnicity (−0.11), nursing role (−0.15), and support (0.29) persisted to significance. A significant decrease (p<0.003) was seen in error reporting after the onset of the Covid-19 pandemic.

Discussion

This is the first study to report SAQ during Covid-19 and compare with baseline. Differences in SAQ scores were observed during Covid-19 between professional groups and compared to baseline. Reductions in incident reporting were also seen. These changes may reflect perception of risk, changes in volume or nature of work. High-quality support for redeployed staff may be associated with improved safety perception during future pandemics.

WHAT IS ALREADY KNOWN ON THE SUBJECT

Safety culture is associated with patient safety and outcomes

This is the first study to investigate safety culture during the Covid-19 pandemic

This study uses the Safety Attitudes Questionnaire (SAQ) and Datix incident reporting data to investigate determinants of safety climate during the Covid-19 pandemic.

Safety climate is context specific, this study is strengthened by the availability of benchmarking data from before the onset of the Covid-19 pandemic.

Significant differences in SAQ scores between professional groups were observed during Covid-19.

Gender, ethnicity and job role were significant determinants of safety attitudes.

Support during redeployment was associated with improved safety attitudes.

The number of incidents that were reported reduced significantly during Covid-19, although the number of events leading to harm remained constant.
Thyroid function abnormalities in COVID-19 patients
Authors: Wang Weibin , Su Xingyun , Ding Yongfeng , Fan Weina , Su Junwei , Chen Zhendong , Zhao Hong , Xu Kaijin , Ni Qin , Xu Xiaowei , Qiu Yunqing , Teng Lisong
Published: June 2020

Background

The novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown.

Methods

84 hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were respectively enrolled in this study. In addition, 91 other patients with pneumonia and 807 healthy subjects were included as controls.

Findings

We found that the levels of TT3 and TSH were lower in COVID-19 patients than control groups (p<0·001). Within the group of COVID-19 patients, 61.9% patients (52/84) presented with thyroid function abnormalities. We found a larger proportion of patients in severe condition exhibited thyroid dysfunction than mild/moderate cases (74·6% vs. 23·8%, p < 0·001). Patients with thyroid dysfunction tended to have increased interval time for negative conversion of viral nucleic acid (14·1 ± 9·4 vs. 10·6 ± 8·3 days, p = 0·088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0·001) and increased CRP (p = 0·002). In 7 patients with dynamic changes of thyroid function, we observed the levels of TT3 and TSH gradually increased and reached normal range without thyroid hormone replacement at Day 30 post-admission. The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time.

Interpretations

Thyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be caused by virus attack and damage to the thyroid-pituitary axis. Therefore, more attention should be paid to thyroid function during treatment of COVID-19, and close follow-up is also needed after discharge.

Funding

This study was supported by Zhejiang Provincial Science and technology department key R & D plan emergency project (No. 2020c03123-8).
Predictive Accuracy of a Hierarchical Logistic Model of Cumulative SARS-CoV-2 Case Growth
Authors: Kriston Levente
Published: June 2020

Background

Infectious disease predictions models, including virtually all epidemiological models describing the spread of the SARS-CoV-2 pandemic up to June 2020, are rarely evaluated. The aim of the present study was to investigate the predictive accuracy of a prognostic model for forecasting the development of the cumulative number of reported SARS-CoV-2 cases in countries and administrative regions worldwide.

Methods

The cumulative number of reported SARS-CoV-2 cases was forecasted in 251 regions with a horizon of two weeks, one month, and two months using a previously described hierarchical logistic model at the end of March 2020. Forecasts were compared to actual observations by using a series of evaluation metrics.

Results

On average, predictive accuracy was very high in nearly all regions at the two weeks forecast, high in most regions at the one month forecast, and notable in the majority of the regions at the two months forecast. Higher accuracy was associated with the availability of more data for estimation and with a more pronounced cumulative case growth from the first case to the date of estimation. In some strongly affected regions, cumulative case counts were considerably underestimated.

Conclusions

With keeping its limitations in mind, the investigated model can be used for the preparation and distribution of resources during the SARS-CoV-2 pandemic. Future research should primarily address the model’s assumptions and its scope of applicability. In addition, establishing a relationship with known mechanisms and traditional epidemiological models of disease transmission would be desirable.
Modelling the Occurrence of the Novel Pandemic COVID-19 Outbreak– A Box and Jenkins Approach
Authors: Nurudeen Ajadi , Adesegun Ogunsola Isqeel , Saddam Damisa Adams
Published: June 2020

The corona virus disease 2019 (COVID-19) is a novel pandemic disease that spreads very fast and causes severe respiratory problem to its carrier and thereby results to death in some cases. In this research, we studied the trend, model Nigeria daily COVID-19 cases and forecast for the future occurrences in the country at large. We adopt the Box and Jenkins approach. The time plot showed that the cases of COVID-19 rises rapidly in recent time. KPSS test confirms the non-stationarity of the process (p < 0.05) before differencing. The test also confirmed the stationarity of the process (p > 0.05) after differencing. Various ARIMA (p,d,q) were examined with their respective AICs and Log-likelihood. ARIMA (1, 2, 1) was selected as the best model due to its least AIC (559.74) and highest log likelihood (−276.87). Both Shapiro-Wilk test and Box test performed confirm the fitness of the model (p > 0.05) for the series. Forecast for 30 days was then made for COVID-19 cases in Nigeria. Conclusively, the model obtained in this research can be used to model, monitor and forecast the daily occurrence of COVID-19 cases in Nigeria.
Recognition memory: familiarity signals increase selectively in the lateral entorhinal cortex following hippocampal lesions
Authors: Mahnke Liv , Atucha Erika , Kitsukawa Takashi , Sauvage Magdalena M.
Published: June 2020

The sense of familiarity for events is crucial for successful recognition memory. However, the neural substrate and mechanisms supporting familiarity remain unclear. Some human and animal studies suggest that the lateral entorhinal (LEC) and the perirhinal (PER) cortices might be essential for familiarity judgments while others attribute this function to the hippocampus (HIP) and it is unclear whether LEC, PER and HIP interact within this frame. Here, we especially investigate if LEC and PER’s contribution to familiarity depends on hippocampal integrity. Using a human to rat translational memory task and high resolution IEG imaging, we report that hippocampal lesions selectively enhance activity in LEC during familiarity judgments. These findings suggest that different mechanisms support familiarity in LEC and PER and, that HIP might exert a tonic inhibition on LEC during recognition memory that might be released when HIP is compromised, possibly constituting a compensatory mechanism in aging and amnesic patients.
Social signaling via bioluminescent blinks drives schooling behavior in the flashlight fishAnomalops katoptron
Authors: Jägers Peter , Wagner Louisa , Schütz Robin , Mucke Maximilian , Senen Budiono , Limmon Gino V. , Herlitze Stefan , Hellinger Jens
Published: June 2020

The bioluminescent flashlight fishAnomalops katoptronlive in schools of several hundred specimens. To understand how flashlight fish, integrate bioluminescent signaling into their schooling behavior, we analyzed movement profiles and blink frequencies. Isolated specimen ofA. katoptronshow a high motivation to align with fixed or moving artificial light organs. Depending on presented frequenciesA. katoptronresponds with a reduction in swimming speed and its own blink frequency. Higher presented blink frequencies reduce the nearest neighbor distance. In the natural environmentA. katoptronis changing its blink frequencies and nearest neighbor distance in a context specific manner. Blink frequencies are increased from day to night and during avoidance behavior, while nearest neighbor distance is decreased with increasing blink frequencies.A. katoptronchanges its blink frequencies by modifying light organ occlusion. Our results suggest that visually transmitted information via specific blink patterns determine intraspecific communication and group cohesion in schoolingA. katoptron.
Giant viruses encode novel types of actins possibly related to the origin of eukaryotic actin: the viractins
Authors: Cunha Violette Da , Gaia Morgan , Ogata Hiroyuki , Jaillon Olivier , Delmont Tom O. , Forterre Patrick
Published: June 2020

Actin is a major component of the eukaryotic cytoskeleton. Many related actin homologues can be found in eukaryotes1, some of them being present in most or all eukaryotic lineages. The gene repertoire of the Last Eukaryotic Common Ancestor (LECA) therefore would have harbored both actin and various actin-related proteins (ARPs). A current hypothesis is that the different ARPs originated by gene duplication in the proto-eukaryotic lineage from an actin gene that was inherited from Asgard archaea. Here, we report the first detection of actin-related genes in viruses (viractins), encoded by 19 genomes belonging to the Imitervirales, a viral order encompassing the giant Mimiviridae. Most viractins were closely related to the actin, contrasting with actin-related genes of Asgard archaea and Bathyarchaea (a newly discovered clade). Our phylogenetic analysis suggests viractins could have been acquired from proto-eukaryotes and possibly gave rise to the conventional eukaryotic actin after being reintroduced into the pre-LECA eukaryotic lineage.
In vivofluorescence lifetime imaging captures metabolic changes in macrophages during wound responses in zebrafish
Authors: Miskolci Veronika , Tweed Kelsey E , Lasarev Michael R , Britt Emily C , McDougal Courtney E , Walsh Alex J , Fan Jing , Sauer John-Demian , Skala Melissa C , Huttenlocher Anna
Published: June 2020

The effector functions of macrophages across the spectrum of activation statesin vitroare linked to profound metabolic rewiring. However, the metabolism of macrophages remains poorly characterizedin vivo. To assess changes in the intracellular metabolism of macrophages in their native inflammatory microenvironment, we employed two-photon fluorescence lifetime imaging microscopy (FLIM) of metabolic coenzymes NAD(P)H and FAD. We found that pro-inflammatory activation of macrophagesin vivowas associated with a decrease in the optical redox ratio [NAD(P)H/(NAD(P)H+FAD)] relative to a pro-resolving population during both infected and sterile inflammation. FLIM also resolved temporal changes in the optical redox ratio and lifetime variables of NAD(P)H in macrophages over the course of sterile inflammation. Collectively, we show that non-invasive and label-free imaging of autofluorescent metabolic coenzymes is sensitive to dynamic changes in macrophage activation in interstitial tissues. This imaging-based approach has broad applications in immunometabolism by probing in real time the temporal and spatial metabolic regulation of immune cell function in a live organism.

Significance

Metabolic regulation of macrophage effector functions has recently emerged as a key concept in immune cell biology. Studies rely onin vitroandex vivoapproaches to study macrophage metabolism, however the high plasticity of these cells suggest that removal from their native microenvironment may induce changes in their intracellular metabolism. Here, we show that fluorescence lifetime imaging microscopy of metabolic coenzymes captures dynamic changes in the metabolic activity of macrophages while maintaining them in their endogenous microenvironment. This approach also resolves variations on a single-cell level, in contrast to bulk measurements provided by traditional biochemical assays, making it a potentially valuable tool in the field of immunometabolism.
Crystal structure of {μ2-1,2-bis[(4-methylphenylsulfanyl]-3-oxoprop-1-ene-1,3-diyl-1:2κ2C3:C1}dicarbonyl-1κ2C-[μ2-methylenebis(diphenylphosphane)-1:2κ2P:P′](triphenylphosphane-2κP)ironplatinum(Fe—Pt), [(OC)2Fe(μ-dppm){μ-C(=O)C(4-MeC6H4SCH2)=CCH2SC6H4Me-4}Pt(PPh3)]
Authors: Mohamed Ahmed Said , Jourdain Isabelle , Knorr Michael , Brieger Lukas , Strohmann Carsten
Published: June 2020

The title compound, [FePt(C19H18OS2)(C18H15P)(C25H22P2)(CO)2],1, [(OC)2Fe(μ-dppm)(μ-C(=O)C(CH2SC6H4Me-4)=CCH2SC6H4Me-4)Pt(PPh3)], represents the first example of a diphosphane-bridged heterobimetallic Fe—Pt dimetallacyclopentenone complex resulting from a bimetallic activation of metal-coordinated carbonyl ligand with an internal alkyne, namely 1,4-bis(p-tolylthio)but-2-yne. The bridging μ2-C(=O)C(CH2SC6H4Me-4)=CCH2SC6H4Me-4 unit (stemming from a carbon–carbon coupling reaction between CO and the triple bond of the alkyne dithioether) forms a five-membered dimetallacyclopentenone ring, in which the C=C bond is π-coordinated to the Fe center. The latter is connected to the Pt center through a short metal–metal bond of 2.5697 (6) Å.
Crystal structure and Hirshfeld surface analysis of 4-{[(E)-4-(heptyloxy)benzylidene]amino}-N-(naphthalen-2-yl)-1,3-thiazol-2-amine
Authors: Sheakh Mohamad Ropak A. , Aziz Hashim J. , Hamad Wali M.
Published: June 2020

In the title compound, C27H28N2OS, the naphthalene unit is planar to within 0.015 (2) Å and makes a dihedral angle of 14.24 (16)° with the thiazole ring. The anisole ring is inclined to the thiazole ring by a dihedral angle of 13.18 (23)°. The torsion angle between the heptyl chain and the anisole ring is 61.1 (4)°. These dihedral and torsion angles render the molecule non-planar. In the crystal, molecules are linked by C—H...π interactions, forming zigzag chains that propagate parallel to the b axis. The roles of the various intermolecular interactions in the crystal packing were clarified by Hirshfeld surface analysis; the most important contributions are from H...H (51.5%) and C...H/H...C (31.8%) contacts.
Ethyl (3S)-3-[(3aR,5R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[4,5-d][1,3]dioxol-5-yl]-3-{(3S)-3-[(3aR,5R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[4,5-d][1,3]dioxol-5-yl]-5-oxoisoxazolidin-2-yl}propanoate chloroform monosolvate
Authors: Amaro Hernández Aldo Guillermo , Rodríguez Tzompantzi Tomasa , Dávila García Álvaro , Meza-León Rosa Luisa , Bernès Sylvain
Published: June 2020

The title compound, C22H33NO12·CHCl3, was obtained as a product of a double aza-Michael addition of hydroxylamine on a Chiron with a known absolute configuration. The enantiopure compound crystallized as a chloroform solvate, in space group P1, and diffraction data were collected at room temperature with Ag Kα radiation. The Flack parameter refined to x = −0.01 (16); however, the Flack and Watkin 2AD plot clearly shows that differences between Friedel opposites (the D component of the plot) do not carry any reliable information about resonant scattering of Cl atoms, and are rather dominated by random and systematic errors. The RD
factor calculated using 1941 acentric Friedel pairs is RD
= 0.995. On the other hand, the 2A component of the plot, related to average intensities of Friedel pairs, shows that data are of good quality (RA
= 0.069). This example illustrates that while using Ag Kα radiation (λ = 0.56083 Å), scatterers heavier than Cl should be present in a chiral crystal in order to determine confidently the absolute structure of the crystal.
Modern globalization: development of glocalization and fragmentation of the world economy
Authors: Arkhipov Alexey Yu. , Yeletsky Alexey N.
Published: June 2020

Purpose

The purpose of the article is to analyze the contradictory trends in the development of the modern world economic system. The relevance of the topic is due to the multifaceted and ambiguous nature of regionalization, glocalization and fragmentation tendencies formed as the most important trends in the crisis of globalism.

Design/methodology/approach

Based on the classical methods of historical and functional analysis, system approach and comparative studies, the authors realized the research potential of modern methodological tools, alternative forecasting methods and comparative modeling, as well as special methods of economic globalistics and global political economy. Heuristic possibilities of the methodological–theoretical concept of glocalization of international economic relations are used.

Findings

New directions and opportunities for attaining regional and global geo-economic leadership are revealed and demonstrated. It is justified that glocalization does not lead to economic isolation in previously known historical forms but to priority realization of the interests of local economic entities included in the processes of globalization and subordinated to its patterns. Glocalization causes an increase in the role of local factors in the global development of the society, in particular of the global economy.

Originality/value

It is established that the so-called equilibrium zones (enjoying the advantages of an intermediary role in the interrelationships of large areas of the world economy, which are headed by geo-economic leaders) possess the potential for novelty in the dynamics of a globalizing economy. The article predicts the formation of a multidimensional and multilevel geo-economic multipolarity due to the reshaping of the global system of leadership in the world economy and due to the contradictory competitive relationships of its main centers.
Examining user satisfaction and stickiness in social networking sites from a technology affordance lens: uncovering the moderating effect of user experience
Authors: Shao Zhen , Zhang Lin , Chen Kuanchin , Zhang Chenliang
Published: June 2020

Purpose

The aim of this study is to explore, identify and understand the impact of technology affordance in the context of social networking sites (SNSs). Moreover, this study incorporates user experience as a moderator, in order to explore behavioral differences between veterans (high-experience users) and newbies (low-experience users).

Design/methodology/approach

A research model was developed to examine the influences of three technology affordances: interactivity, information and navigation on user satisfaction and SNS stickiness. Totally 266 data were collected from a famous college in China using an online survey, and structural equation modeling technique was used to examine the proposed research model.

Findings

The empirical research findings indicated that the three technology affordance attributes exhibited different degrees of influence on user satisfaction, which in turn facilitated SNS stickiness. Particularly, high-experience users were more likely influenced by interactivity and information affordances, while low-experience users are more susceptible to navigation affordance.

Practical implications

This study can provide guidelines to the platform administrators to design SNSs from the aspects of interactivity, information and navigation attributes and pay attention to the preference differences between high-experience users and low-experience users.

Originality/value

This study uncovers the significant antecedents of SNS stickiness from a technology affordance lens and reveals the moderating effect of user experience on the relationship between three technology affordance attributes and satisfaction.
Key sources of operational inefficiency in the pharmaceutical supply chain
Authors: Papalexi Marina , Bamford David , Breen Liz
Published: June 2020

Purpose

This study aims to explore the downstream pharmaceutical supply chain (PSC) and provides insight to the delivery process of medicines and associated operational inefficiencies.

Design/methodology/approach

An exploratory, qualitative approach was adopted to examine PSC inefficiency within two European contexts, namely, the UK and Greece. Data was gathered through interviews and a thematic analysis conducted to analyse the data and identify challenges faced by both supply chains(SCs).

Findings

The medicines delivery system needs to be enhanced in terms of quality, visibility, speed and cost to perform effectively. The findings demonstrated that although the healthcare SCs in the two European contexts have different operational structures, the results are in concordance with each other. Financial, communication, waste and complexity issues were the major concerns.

Research limitations/implications

To the knowledge this is the first study to examine aspects of the medicines SC via a cross-case analysis in the UK and Greece and extends the body of knowledge. A broader sample of responses is warranted to further validate these findings.

Practical implications

The study outputs can inform pharmacies’ strategic to instigate targeted improvement interventions. The implications of which may be extrapolated further to other European healthcare organisations.

Originality/value

This research contributes to the academic literature by adding further theoretical insights to SC strategy development, especially those that have been characterised as highly complex. The study identifies four key areas of intervention needed within this SC (in both countries) to promote higher level efficiencies and effectiveness.
Integrated strategy combining endobronchial ultrasound with positron emission tomography to diagnose peripheral pulmonary lesions
Authors: Wu Xiao , An Zhou , Zhao Kui , Yang Sijia , Lin Xu , Dai Xiaona , Radisky Derek , Hu Jian
Published: June 2020

Background

Endobronchial ultrasound‐guided transbronchial lung biopsy (EBUS‐TBLB) and fluorodeoxyglucose positron emission tomography (FDG‐PET) have been widely used in the diagnosis of peripheral pulmonary lesions (PPLs). This study was conducted to determine the diagnostic value of EBUS‐TBLB combined with FDG‐PET in the assessment of PPLs.

Methods

The clinical data of 76 patients with PPLs who received both FDG‐PET and EBUS‐TBLB from January 2016 to February 2018 were retrospectively evaluated. Further subgroup analysis was performed according to lesion diameter (≤20 mm or >20 mm). Related diagnostic indices were calculated and compared between groups.

Results

When combining EBUS‐TBLB with FDG‐PET, the diagnostic accuracy rate, sensitivity, specificity, Youden's index, positive predictive value, and negative predictive value for PPLs were 86.8%, 90.2%, 73.3%, 63.5%, 93.2%, and 64.7%, respectively. In addition, the diagnostic accuracy rate of the combined approach was significantly higher than the single EBUS‐TBLB and FDG‐PET (P < 0.01 and P < 0.05, respectively), and its Youden's index was also at a higher level. When stratified by lesion diameter, the combined approach showed a significantly higher diagnostic accuracy rate (P < 0.05) and a higher Youden's index for PPLs >20 mm than PPLs ≤20 mm. In addition, we found that positive bronchus sign and probe within the probe were two important factors conducing to enhancing the diagnostic accuracy rate for EBUS‐TBLB.

Conclusions

An integrated approach combining EBUS‐TBLB with FDG‐PET is particularly useful for diagnosing PPLs, and the improved diagnostic yields were especially evident for PPLs >20 mm.
Association of two novel viruses with chlorotic fleck disease of ginger
Authors: Bhat Alangar Ishwara , Naveen Kadambath Palasseri , Pamitha Nedungottil Sankaranarayanan , Pant Rajendra Prasad
Published: June 2020

Chlorotic fleck disease of ginger, the causal virus of which was unknown so far is an important production constraint of ginger in India and other parts of the world. In the present study, two new RNA viruses were discovered in chlorotic fleck affected plant by the virome analysis using high‐throughput sequencing (HTS) of small RNA and transcriptome. The HTS results were verified through reverse transcriptase polymerase chain reaction (RT‐PCR) using total RNA from infected plants and primers designed from the contigs. Cloning and sequencing of the RT‐PCR products of one of the viruses resulted in a sequence of 4,143 bases that showed similarities to panicoviruses and machlomoviruses. The complete genome of this virus contained six open reading frames (ORFs) that potentially encode proteins of 43, 104, 8, 7, 15 and 27 kDa. Based on the genomic and phylogenetic analysis, this virus is predicted to be a new member of the family Tombusviridae for which the name ginger chlorotic fleck‐associated virus 1 is proposed. Similarly, cloning and sequencing of the RT‐PCR products of the other virus resulted in a sequence of 5,514 bases that showed similarities to ampeloviruses. Based on the genomic and phylogenetic analysis, this virus is predicted to be a new member of the genus Ampelovirus for which the name ginger chlorotic fleck‐associated virus 2 is proposed. Reliable RT‐PCR and SYBR Green‐based quantitative RT‐PCR assays were developed for the detection of both viruses in plants that would aid in the identification and propagation of virus‐free ginger plants. Additional investigations are required to elucidate the relationship between the symptoms and viral infections.
Appropriate care for neonates born to mothers with COVID‐19 disease
Authors: Tran Hoang Thi , Nguyen Phuong Thi Kim , Huynh Le Thi , Le Chau Hoang Minh , Giang Hoang Thi Nam , Nguyen Phuong Thi Thu , Murray John
Published: June 2020

The global COVID‐19 pandemic has been associated with high rates of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission, morbidity and mortality in the general population. Evidence‐based guidance on caring for babies born to mothers with COVID‐19 is needed. There is currently insufficient evidence to suggest vertical transmission between mothers and their newborn infants. However, transmission can happen after birth from mothers or other carers. Based on the currently available data, prolonged skin‐to‐skin contact and early and exclusive breastfeeding remain the best strategies to reduce the risks of morbidity and mortality for both the mother with COVID‐19 and her baby.
Customised pediatric palliative care: Integrating oncological and palliative care priorities
Authors: Podda Marta , Schiavello Elisabetta , Visconti Giovanna , Clerici Carlo Alfredo , Armiraglio Mariangela , Casiraghi Giovanna , Ambroset Sonia , Grossi Alberto , Rizzi Barbara , Lonati Giada , Massimino Maura
Published: June 2020

Aim

To describe the experience involving the early introduction of palliative care (PC) in oncological patients treated within the paediatric oncology unit of the Istituto Nazionale Tumori of Milan and compare this cohort with a cohort of patients resident in the same area treated before the introduction of early palliative care.

Methods

A virtual team was assembled in 2015. The PC providers operate outside the hospital. Conference calls were scheduled to discuss patients’ problems. This sample was compared with the clinical records of patients residing in the same area who died between 2009 and 2014.

Results

Between January 2015 and April 2019, 41 patients residing in the Milan area mainly with CNS tumours or sarcomas were referred to the team. Comparing the results with the previous cohort, there was a rise in the number of patients dying at home or in a hospice and the duration of PC increased over time. From 2015, none of the patients died in an intensive care unit.

Conclusion

Patients managed by the virtual team were able to continue their cancer treatments, take part in Phase I trialsandreceive PC. All patients with a poor prognosis should have PC at an early stage.
Curcumin in antidepressant treatments: An overview of potential mechanisms, pre‐clinical/clinical trials and ongoing challenges
Authors: Zhang Yinfeng , Li Li , Zhang Jinfeng
Published: June 2020

Depression is one of the most common but serious psychiatric disorders affecting millions of people globally, which has become increasingly prevalent during the past few decades. To alleviate this challenging health and social burden, various therapeutic strategies have been developed to achieve efficient treatments for depression. In particular, plenty of chemical ingredients of natural origin have been investigated as new direct antidepressants or served as adjuvants to improve the current treatment outcomes of existing antidepressant drugs. Among them, curcumin, a natural compound derived from the herbCurcuma longa, exhibits a wide range of pharmacological properties and has been considered a potent antidepressant drug with diverse mechanisms including monoaminergic imbalances (associated with serotonin, dopamine, noradrenaline and glutamate), effect on neurotransmitters, neuroprogression, the hypothalamic‐pituitary‐adrenal (HPA) axis disturbances, dysregulated inflammation and immune pathways, oxidative and nitrosative stress, and mitochondrial disturbances. In this review, multiple potential mechanisms of curcumin for treating depression demonstrated in either animal or human studies are summarized. To better understand the significant role of curcumin, specific emphasis will be placed on the aetiopathogenesis of depression. Finally, current pre‐clinical/clinical trials and ongoing challenges of curcumin used for antidepressant treatments will be discussed and their future outlooks will be briefly presented.
Primary mediastinal choriocarcinoma presenting as cutaneous metastasis with resistance to chemotherapy: case report and literature review
Authors: Murshed Khaled A. , Kanbour Aladdin , Akhtar Mohammed , Al Hyassat Samir
Published: June 2020

Cutaneous metastases of choriocarcinoma are rare. They may indicate poor prognosis and resistance to chemotherapy. In this report, we present a case of a 25‐year‐old man who presented with central pleuritic chest pain and right upper arm mass for about a week. The patient also had significant weight loss during the last 5 months along with an episode of generalized seizure. Chest computed tomography scan revealed an 8 cm anterior mediastinal mass. A skin punch biopsy from the right upper arm mass revealed a malignant neoplasm with morphology consistent with metastatic choriocarcinoma. Further work‐up revealed multiple lung and brain lesions. Ultrasound of the testes revealed no abnormalities. Several chemotherapy regimens were tried; however, there was no response and the disease showed progression. The patient died 6 months after initial presentation.
Recommendations for the medical work‐up of first episode psychosis, including specific relevance to Indigenous Australians: A narrative review
Authors: Dorney Kiernan , Murphy Michael
Published: June 2020

Aims

To collate existing literature for busy practicing psychiatrists about the medical work‐up for first‐episode psychosis (FEP). Therefore, (a) to review current guidelines for the medical work‐up of first episode psychosis. (b) To examine whether any specific recommendations for Indigenous Australians exist. (c) To produce an easy reference table of evidence based investigations.

Method

A multi‐part narrative review process was undertaken. Step 1 “Source identification and summary”: identified key existing national and international guidelines and expert opinions related to the medical work‐up of FEP and summarised these suggestions. Step 2 “Exploration of each investigation”: examined each of the identified investigations for its importance. Step 3 “Relevance to Indigenous Australians”: reviewed any particular relevance to the Indigenous Australian population. Step 4 “Clinician guide”: involved presenting recommended investigations in a simple table.

Results

Multiple guidelines were identified. There was clear consensus for many aspects. However, there were also differences in the approach for some investigations. Clinical reasoning for the proposed investigations was commonly absent. There were limited specific recommendations for Indigenous Australians. Evidence and importance was explored for each investigation and auseful table for the practicing psychiatrist was constructed. Investigations were stratified into those considered to be “universal,” “low yield,” or “unecessary.”

Conclusion

A narrative review of multiple guidelines relating to the medical work‐up of FEP identified many similarities and some differences to their approach. Little additional information exists for the Indigenous Australian context. A clinician friendly worksheet for everyday use may be helpful to busy clinicians.
High adherence to prophylaxis regimens in haemophilia B patients receiving rIX‐FP: Evidence from clinical trials and real‐world practice
Authors: Mancuso Maria Elisa , Oldenburg Johannes , Boggio Lisa , Kenet Gili , Chan Anthony , Altisent Carmen , Seifert Wilfried , Santagostino Elena
Published: June 2020

Introduction

Adherence to prophylaxis regimens is essential for bleed prevention in haemophilia but remains a challenge due to the need for frequent infusions.

Aim

To evaluate patient adherence to prophylaxis regimens with a long‐acting recombinant factor IX (rIX‐FP; IDELVION®) in clinical studies and real‐world practice.

Methods

In two phase 3 clinical studies, patients with haemophilia B (FIX ≤2%) recorded their dose, dosing frequency and rIX‐FP consumption in an e‐diary. Adherence to prescribed prophylaxis regimens was assessed in all patients and to prescribed dose in patients ≥12 years only. Additionally, adherence to rIX‐FP prophylaxis regimens in real‐world practice was captured.

Results

In clinical studies, 94.9% (n = 56/59) of patients ≥12 years and 100% (n = 27) of paediatric patients received ≥80% of the expected number of infusions for their assigned prophylaxis schedule. Overall, mean adherence rate was 95.5% across all prophylaxis regimens in patients ≥12 years and 97.9% with a 7‐day regimen in paediatric patients. In patients ≥12 years, 85.7% (n = 54/63) were dose adherent, defined as receiving within 10% of their prescribed dose ≥80% of the time. In real‐world practice, adherence was observed in 100% (n = 14 and n = 15, respectively) of patients in two haemophilia treatment centres and 57.1% (n = 4/7) of patients in a third centre; non‐adherence (n = 3/7) was linked to insurance‐related and parental issues.

Conclusion

In clinical studies, patients with haemophilia B had high adherence rates to rIX‐FP prophylaxis regimens with a variety of dosing intervals, enabling them to achieve very low bleeding rates. High adherence may also be achievable in real‐world practice.
Endolymphatic Hydrops Secondary to Spontaneous Intracranial Hypotension
Authors: Poillon Guillaume , Hautefort Charlotte , Levy Daniel , Eliezer Michael
Published: June 2020

Background

Spontaneous intracranial hypotension may be associated with neuro‐otological symptoms that might mimic Menière’s disease.

Case Presentation

We report the case of a 53‐year‐old male presenting bi‐frontal headache with recurrent spells of vertigo, left fluctuating hearing loss, and tinnitus. Dedicated brain and inner ear Magnetic Resonance Imaging, including a post‐contrast 4 hours delayed FLAIR sequence, revealed typical signs of spontaneous intracranial hypotension associated with endolymphatic hydrops involving the left saccule and cochlea.

Conclusions

Audio vestibular manifestations mimicking Menière's disease in spontaneous intracranial hypotension could be explained by endolymphatic hydrops, which can be detected using dedicated magnetic resonance imaging sequences.
COVID‐19 research: an opinion piece
Authors: Waters L , Rockstroh JK
Published: June 2020

The unprecedented global scale of COVID‐19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarize the evidence for antiretrovirals to treat COVID‐19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.