bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma
Authors: Schritz Anna , Aouali Nassera , Fischer Aurélie , Dessenne Coralie , Adams Roisin , Berchem Guy , Huiart Laetitia , Schmitz Susanne
Published: April 2021

Background

Despite advances in the treatment of cancers over the last years, treatment options for patients with recurrent glioblastoma (rGBM) remain limited with poor outcomes. Many regimens have been investigated in clinical trials; however, there is a lack of knowledge on comparative effectiveness. The aim of this systematic review is to provide an overview of existing treatment strategies and to estimate the relative efficacy of these regimens in terms of progression-free survival (PFS) and overall survival (OS).

Methods

We conducted a systematic review to identify randomized controlled trials (RCTs) investigating any treatment regimen in adult patients suffering from rGBM. Connected studies reporting at least one of our primary outcomes were included in a Bayesian network meta-analysis (NMA) estimating relative treatment effects.

Results

Forty RCTs fulfilled our inclusion criteria evaluating the efficacy of 38 drugs as mono- or combination therapy. Median OS ranged from 2.9 to 18.3 months; median PFS ranged from 0.7 to 6 months. We performed an NMA including 24 treatments that were connected within a large evidence network. Our NMA indicated improvement in PFS with most bevacizumab (BV)-based regimens compared to other regimens. We did not find any differences in OS between treatments.

Conclusion

This systematic review provides a comprehensive overview of existing treatment options for rGBM. The NMA provides relative effects for many of these treatment regimens, which have not been directly compared in RCTs. Overall, outcomes for patients with rGBM remain poor across all treatment options, highlighting the need for innovative treatment options.
SARS-CoV-2 Vaccination During Pregnancy: A Complex Decision
Authors: Wang Elizabeth Wenqian , Parchem Jacqueline G , Atmar Robert L , Clark Eva H
Published: April 2021

As the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines passed UK and US regulatory milestones in late 2020 and early 2021, multiple professional societies offered recommendations to assist pregnant and breastfeeding people as they choose whether to undergo vaccination. Despite such guidance, the lack of data describing vaccine safety, immunogenicity, and efficacy in pregnant and breastfeeding people has made this decision challenging for many. However, even considering the paucity of data, the known risks of coronavirus disease 2019 during pregnancy likely outweigh the not yet fully elucidated risks of SARS-CoV-2 vaccines, which have reassuring safety and efficacy profiles among nonpregnant people.
T-follicular helper cells in malaria infection and roles in antibody induction
Authors: Soon Megan S F , Nalubega Mayimuna , Boyle Michelle J
Published: April 2021

Immunity to malaria is mediated by antibodies that block parasite replication to limit parasite burden and prevent disease. Cytophilic antibodies have been consistently shown to be associated with protection, and recent work has improved our understanding of the direct and Fc-mediated mechanisms of protective antibodies. Antibodies also have important roles in vaccine-mediated immunity. Antibody induction is driven by the specialized CD4+ T cells, T-follicular helper (Tfh) cells, which function within the germinal centre to drive B-cell activation and antibody induction. In humans, circulating Tfh cells can be identified in peripheral blood and are differentiated into subsets that appear to have pathogen/vaccination-specific roles in antibody induction. Tfh cell responses are essential for protective immunity from Plasmodium infection in murine models of malaria. Our understanding of the activation of Tfh cells during human malaria infection and the importance of different Tfh cell subsets in antibody development is still emerging. This review will discuss our current knowledge of Tfh cell activation and development in malaria, and the potential avenues and pitfalls of targeting Tfh cells to improve malaria vaccines.
The spatial structure and dynamical state of the open cluster NGC 2112
Authors: Gao Xinhua , Xu ShouKun , Xue Lei
Published: April 2021

This paper investigates the spatial structure and dynamical state of the old open cluster NGC 2112 based on likely cluster members from Gaia Early Data Release 3. Using the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm, we find 1193 likely cluster members down to G ∼ 21 mag within a radius of 1.°5 from the cluster center. These likely cluster members can be divided into 865 core members and 328 border members by DBSCAN. We find that the core members are, on average, significantly brighter and more centrally concentrated than the border members. This suggests the existence of clear mass segregation within the cluster. We find that the outer regions of the cluster exhibit a slightly elongated shape, which may be caused by external tidal perturbations. We estimate a distance of D = 1108 ± 3 pc for the cluster based on bright core members. We find that NGC 2112 has a cluster radius of Rcl ∼ 40′ (∼12.9 pc) and a core radius of $R_{\rm c} \sim {4{^{\prime }_{.}}8} \pm {0{^{\prime }_{.}}2}$ (∼1.5 pc). This indicates that NGC 2112 has a central concentration parameter of C = log (Rcl/Rc) ∼ 0.92, which is significantly larger than previously thought. In addition, we estimate a total mass of Mcl = 858 ± 12 M⊙ and an initial mass of Mini = (2.2 ± 0.5) × 104 M⊙ for the cluster. This implies that NGC 2112 may have lost more than $90\%$ of its initial mass. Based on the obtained distance and kinematical data, we also calculate the Galactic orbit of the cluster.
The relationship between fasting-induced torpor, sleep, and wakefulness in laboratory mice
Authors: Huang Yi-Ge , Flaherty Sarah J , Pothecary Carina A , Foster Russell G , Peirson Stuart N , Vyazovskiy Vladyslav V
Published: April 2021

Study Objectives

Torpor is a regulated and reversible state of metabolic suppression used by many mammalian species to conserve energy. Whereas the relationship between torpor and sleep has been well-studied in seasonal hibernators, less is known about the effects of fasting-induced torpor on states of vigilance and brain activity in laboratory mice.

Methods

Continuous monitoring of electroencephalogram (EEG), electromyogram (EMG), and surface body temperature was undertaken in adult, male C57BL/6 mice over consecutive days of scheduled restricted feeding.

Results

All animals showed bouts of hypothermia that became progressively deeper and longer as fasting progressed. EEG and EMG were markedly affected by hypothermia, although the typical electrophysiological signatures of non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and wakefulness enabled us to perform vigilance-state classification in all cases. Consistent with previous studies, hypothermic bouts were initiated from a state indistinguishable from NREM sleep, with EEG power decreasing gradually in parallel with decreasing surface body temperature. During deep hypothermia, REM sleep was largely abolished, and we observed shivering-associated intense bursts of muscle activity.

Conclusions

Our study highlights important similarities between EEG signatures of fasting-induced torpor in mice, daily torpor in Djungarian hamsters and hibernation in seasonally hibernating species. Future studies are necessary to clarify the effects on fasting-induced torpor on subsequent sleep.
Curcumin nicotinate suppresses abdominal aortic aneurysm pyroptosis via lncRNA PVT1/miR-26a/KLF4 axis through regulating the PI3K/AKT signaling pathway
Authors: Xiong Jian-Ming , Liu Hui , Chen Jie , Zou Qing-Qing , Wang Yang-Yi-Jing , Bi Guo-Shan
Published: April 2021

Abdominal aortic aneurysm (AAA) is a chronic dilated disease of the aorta that is characterized by chronic inflammation. Curcumin (Cur) is previously showed to attenuate AAA by inhibiting inflammatory response in ApoE −/− mice. Since Cur has the limitations of aqueous solubility and instability. Here, we focus on the role of curcumin nicotinate (CurTn), a Cur derivative is derived from Cur and nicotinate. An in vitro model of AAA was established by treating vascular smooth muscle cells (VSMCs) with II (Ang-II). Gene and protein expressions were examined by quantitative real-time PCR (qPCR) or western blotting. Cell migration and pyroptosis were determined by transwell assay and flow cytometry. The interaction between plasmacytoma variant translocation 1 (PVT1), miR-26a and krüppel-like factor 4 (KLF4) was predicted by online prediction tool and confirmed by luciferase reporter assay. CurTn reduced Ang-II-induced AAA-associated proteins, inflammatory cytokine expressions, and attenuated pyroptosis in VSMCs. PVT1 overexpression suppressed the inhibitory effect of CurTn on AngII-induced pyroptosis and inflammatory in VSMCs by sponging miR-26a. miR-26a directly targeted KLF4 and suppressed its expression, which eventually led to the deactivation of the PI3K/AKT signaling pathway. Besides, the regulatory effect of CurTn on pyroptosis of VSMCs induced by Ang-II was reversed through the PVT1/miR-26a/KLF4 pathway. In short, CurTn suppressed VSMCs pyroptosis and inflammation though mediation PVT1/miR-26a/KLF4 axis by regulating the PI3K/AKT signaling pathway, CurTn might consider as a potential therapeutic target in the treatment of AAA.
Redondoviridae and periodontitis: a case–control study and identification of five novel redondoviruses from periodontal tissues
Authors: Zhang Yu , Wang Chunmei , Feng Xiping , Chen Xi , Zhang Wen
Published: April 2021

Redondoviridae is a family of DNA viruses recently identified in the human oro-respiratory tract. However, the characteristics of this new virus family are not yet fully understood. The aim of the present study was to investigate the relationship between redondoviruses and chronic periodontitis. In addition, the complete circular genome, phylogenetic relationship, and biological characteristics of novel redondoviruses were analyzed. The gingival tissues of healthy individuals (n = 120) and periodontitis patients (n = 120) were analyzed using nested polymerase chain reaction assays. The prevalence of redondovirus infection in the periodontitis group was 71.67%. Logistic regression analysis revealed an association between redondoviruses and chronic periodontitis after controlling the confounding factors (odds ratio = 2.53). Five novel redondoviruses, named ‘human periodontal circular-like virus (HPeCV)’, were identified in patients with periodontitis and detailed genetic analysis of the viruses was performed. The 3,035–3,056 bp genome contained a capsid protein, a replication-associated protein, an open reading frame 3 protein, and a stem-loop structure. Phylogenetic analysis demonstrated that HPeCV-1, HPeCV-10, and HPeCV-25 formed a cluster. Recombination may be common in the genomes of HPeCVs. Potential antigenic epitopes in the capsid protein, which may be involved in the host immune response, were predicted. In conclusion, periodontitis patients had a significantly higher prevalence of redondoviruses than healthy controls. Genetic characterization enhanced the current understanding of the genetic diversity and pathogenicity of redondoviruses as well as their association with periodontitis in humans. The data presented in this article will expand the current understanding of the epidemiology, genetic diversity, and pathogenicity of redondoviruses.
The Value of an Orthoplastic Approach to Management of Lower Extremity Trauma: Systematic Review and Meta-analysis
Authors: Klifto Kevin M. , Azoury Saïd C. , Othman Sammy , Klifto Christopher S. , Levin L. Scott , Kovach Stephen J.
Published: April 2021

Background:

Management of traumatic lower extremity injuries requires a skill set of orthopedic surgery and plastic surgery to optimize the return of form and function. A systematic review and meta-analysis was performed comparing demographics, injuries, and surgical outcomes of patients sustaining lower extremity traumatic injuries receiving either orthoplastic management or nonorthoplastic management.

Methods:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis, Cochrane, and GRADE certainty evidence guidelines were implemented for the structure and synthesis of the review. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and CINAHL databases were systematically and independently searched. Nine studies published from 2013 through 2019 compared 1663 orthoplastic managed patients to 692 nonorthoplastic managed patients with traumatic lower extremity injuries.

Results:

Orthoplastic management, compared to nonorthoplastic management likely decreases time to bone fixation [standard mean differences: −0.35, 95% confidence interval (CI): −0.46 to −0.25, P < 0.0001; participants = 1777; studies = 3; I2 = 0%; moderate certainty evidence], use of negative pressure wound therapy [risk ratios (RR): 0.03, 95% CI: 0.00–0.24, P = 0.0007; participants = 189; studies = 2; I2 = 0%; moderate certainty evidence] with reliance on healing by secondary intention (RR: 0.02, 95% CI: 0.00–0.10, P < 0.0001; participants = 189; studies = 2; I2 = 0%; moderate certainty evidence), and risk of wound/osteomyelitis infections (RR: 0.37, 95% CI: 0.23–0.61, P < 0.0001; participants = 224; studies = 3; I2 = 0%; moderate certainty evidence). Orthoplastic management likely results in more free flaps compared to nonorthoplastic management (RR: 3.46, 95% CI: 1.28–9.33, P = 0.01; participants = 592; studies = 5; I2 = 75%; moderate certainty evidence).

Conclusion:

Orthoplastic management of traumatic lower extremity injuries provides a synergistic model to optimize and expedite definitive skeletal fixation and free flap-based soft-tissue coverage for return of extremity form and function.
Adverse Events Associated With Therapeutic Endoscopic Retrograde Pancreatography
Authors: Han Samuel , Attwell Augustin R. , Tatman Philip , Edmundowicz Steven A. , Hammad Hazem T. , Wagh Mihir S. , Wani Sachin , Shah Raj J.
Published: April 2021

Objectives

Data regarding the safety of endoscopic retrograde pancreatography (ERP) are limited compared with biliary endoscopic retrograde cholangiopancreatography. The aim of this study was to determine adverse events (AEs) associated with therapeutic ERP.

Methods

This single-center retrospective study examined consecutive therapeutic ERPs with the primary intention of cannulating the pancreatic duct. Multivariate logistic regression was performed to identify risk factors for AEs.

Results

A total of 3023 ERPs were performed in 1288 patients (mean age, 50.3 years; 57.8% female) from January 2000 to January 2017. Overall AE rate was 18.9% with abdominal pain requiring admission (9.8%) and post-ERP pancreatitis (5.7%) being most common. On multivariate analysis, female sex (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9–2.9), acute recurrent pancreatitis (aOR, 5.0; 95% CI, 1.7–15.3), chronic pancreatitis (aOR, 1.8; 95% CI, 1.3–2.6), and pancreatic sphincter of Oddi dysfunction (aOR, 2.1; 95% CI, 1.4–3.3) were associated with an increased risk of overall AEs. Pancreatic sphincterotomy (aOR, 1.9; 95% CI, 1.5–2.4) and therapeutic stenting (aOR, 1.6; 95% CI, 1.2–2.2) also increased the risk of AEs.

Conclusions

Nearly 1 in 5 patients who undergo therapeutic ERP will experience an AE; however, the rates of major AEs, including post-ERP pancreatitis, bleeding, and perforation, are low.
Updated Meta-analysis of Minimally Invasive Versus Open Surgery for Pancreatic Neuroendocrine Neoplasms
Authors: Zhang Wei , Zhang Jianwei , Che Xu
Published: April 2021

Objectives

The aim of this study was to compare the short-term and long-term outcomes of minimally invasive surgery (MIS) with those of open pancreas surgery (OPS) for the treatment of pancreatic neuroendocrine neoplasms (pNENs).

Methods

Studies reporting the effects of MIS and OPS for pNENs, published on PubMed, Embase, and Cochrane Library before May 2020 were reviewed.

Results

Seventeen cohort studies with a total of 1853 patients were eligible for analysis, including 655 patients in the MIS group and 1198 patients in the OPS group. The estimated blood loss, postoperative hospitalization time, overall complications, severe complications, spleen preservation, mortality, and recurrence in the MIS group were lower than those in the OPS group. The R0 rate, 3-year overall survival (OS), and 5-year OS in the MIS group were higher than those in the OPS group. There were no significant differences in operative time, postoperative pancreatic fistula, clinical postoperative pancreatic fistula, postoperative bleeding, reoperation, readmission, and 1-year OS.

Conclusions

Minimally invasive surgery can reach lower recurrence rate, higher long-term survival rate, and better outcomes in terms of estimated blood loss, postoperative hospitalization time, R0 rate, mortality, overall complications, and severe complications for pNENs. More high quality studies need to be conducted for further verification.
Antibody Responses in Elderly Residential Care Persons following COVID-19 mRNA Vaccination
Authors: Nace David A. , Kip Kevin E. , Palmer Octavia M. Peck , Shurin Michael R. , Mulvey Katie , Crandall Melissa , Kane April L. , Lukanski Amy , Kip Paula L. , Wells Alan L.
Published: April 2021

Objective

COVID-19 disproportionately impacts older adults residing at long-term care facilities. Data regarding antibody response to COVID-19 vaccines in this population is limited. Our objective was to quantify the presence and magnitude of antibody response in older, vaccinated residents at assisted living, personal care, and independent living facilities.

Design

A cross-sectional quality improvement study was conducted March 15 – April 1, 2021 in the Pittsburgh region.

Setting and Population

Participants were volunteers at assisted living, personal care, and independent living facilities, who received mRNA COVID-19 vaccine. Conditions that obviate immune responses were exclusionary criteria.

Methods

Sera were collected to measure IgG anti-SARS-CoV-2 antibody level with reflex to total anti-SARS-CoV-2 immunoglobulin levels. Descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis were performed to evaluate relationships between factors potentially associated with antibody levels.

Results

All participants (N=70) had received two rounds of vaccination for COVID-19 and were found to have antibodies to SARS-CoV-2. There was wide variation in relative levels of antibodies as determined by extinction coefficients. Antibody levels trended lower in male sex, advanced age, steroid medications, and longer length of time from vaccination.

Conclusions and Implications

Higher functioning long-term care residents mounted detectable antibody responses when vaccinated with COVID-19 mRNA-based vaccines. This study provides preliminary information on level of population risk of assisted living, personal care, and independent living residents which can inform reopening strategies. Data suggests some degree of immunity is present during the immediate period following vaccination. However, protective effects of such vaccination programs remain to be determined in larger studies. Clinical protection is afforded not just by pre-formed antibody levels, but by ongoing adaptive immunity, which is known to be decreased in older individuals. Thus, the implications of these levels of antibodies in preventing COVID-19 disease must be determined by clinical follow-up.
A rare congenital anemia is caused by mutations in the centralspindlin complex
Authors: Wontakal Sandeep N. , Britto Mishan , Tannenbaum Sarah , Durham Benjamin H. , Lee Margaret T. , Mishima Masanori
Published: April 2021

Congenital dyserythropoietic anemias (CDAs) are rare disorders characterized by morphologic abnormalities of erythroid precursors leading to ineffective erythropoiesis. CDA type III (CDAIII), characterized by erythroblast multinucleation, represents the rarest form with only ∼60 patients described in the literature. Previous work, studying two independent families, identified a causative dominant missense mutation in KIF23, which encodes for the kinesin MKLP1. Here, we describe a sporadic CDAIII case associated with compound heterozygous variants in RACGAP1, a gene not previously associated with any disease. RACGAP1 encodes CYK4, a GTPase activating protein (GAP) for Rho-family GTPases, which interacts with MKLP1 to form the centralspindlin complex. Functional assays show these RACGAP1 variants cause cytokinesis defects due, at least in part, to altering the substrate specificities of the GAP activity of CYK4. These findings provide novel insights into the structural determinants of the GAP activity and demonstrates that cytokinesis failure due to centralspindlin defects leads to CDAIII. Our findings highlight the importance of viewing diseases as malfunctions of common biological pathways/complexes and suggests that next-generation sequencing analysis pipelines should integrate a systems approach in order to identify such functionally related variants.
Metabolomics strategy for diagnosing urinary tract infections
Authors: Gregson Daniel B. , Wildman Spencer D. , Chan Carly C.Y. , Bihan Dominique G. , Groves Ryan A. , Aburashed Raied , Rydzak Thomas , Pittman Keir , Van Bavel Nicolas , Lewis Ian A.
Published: April 2021

Metabolomics has emerged as a mainstream approach for investigating complex metabolic phenotypes but has yet to be integrated into routine clinical diagnostics. Metabolomics-based diagnosis of urinary tract infections (UTIs) is a logical application of this technology since microbial waste products are concentrated in the bladder and thus could be suitable markers of infection. We conducted an untargeted metabolomics screen of clinical specimens from patients with suspected UTIs and identified two metabolites, agmatine and N6-methyladenine, that are predictive of culture positive samples. We developed a 3.2-minute LC-MS assay to quantify these metabolites and showed that agmatine and N6-methyladenine correctly identify UTIs caused by 13Enterobacteralesspecies and 3 non-Enterobacteralesspecies, accounting for over 90% of infections (agmatine AUC > 0.95; N6-methyladenine AUC > 0.89). These markers were robust predictors across two blinded cohorts totaling 1,629 patient samples. These findings demonstrate the potential utility of metabolomics in clinical diagnostics for rapidly detecting UTIs.
Novel, User-friendly Experimental and Analysis Strategies for Fast Voltammetry: 1. “The Analysis Kid” for FSCV
Authors: Mena Sergio , Dietsch Solene , Berger Shane N. , Witt Colby E. , Hashemi Parastoo
Published: April 2021

Fast-scan cyclic voltammetry at carbon fiber microelectrodes measures low concentrations of analytes in biological systems. There are ongoing efforts to simplify FSCV analysis and several custom platforms are available for filtering and multi-modal analysis of FSCV signals but there is no single, easily accessible platform that has capacity for all these features. Here we presentThe Analysis Kid: a free, open-source cloud application that does not require a specialized runtime environment and is easily accessible via common browsers. We show that a user-friendly interface can analyze multi-platform file formats to provide multimodal visualization of FSCV color plots with digital background subtraction. We highlight key features that allow interactive calibration and parametric analysisviapeak finding algorithms to automatically detect the maximum amplitude, area under the curve and clearance rate of the signal. Finally,The Analysis Kidenables semi-automatic fitting of data with Michaelis Menten kinetics with single or dual reuptake models.The Analysis Kidcan be freely accessed athttps://analysis-kid.herokuapp.com/. The web application code is found, under an MIT license, athttps://github.com/sermeor/The-Analysis-Kid.
Multi-parameter photon-by-photon hidden Markov modeling
Authors: Harris Paul David , Narducci Alessandra , Gebhardt Christian , Cordes Thorben , Weiss Shimon , Lerner Eitan
Published: April 2021

Single-molecule Förster resonance energy transfer (smFRET) is a unique biophysical approach for studying conformational dynamics in biomacro-molecules. Photon-by-photon hidden Markov modelling (H2MM) is an analysis tool that can quantify FRET dynamics of single biomolecules, even if they occur on the sub-millisecond timescale. However, dye photophysical transitions intertwined with FRET dynamics may introduce artefacts. Here, we introduce multi-parameter H2MM (mpH2MM), which assists in identifying FRET dynamics based on simultaneous observation of multiple experimentally-derived parameters. We show the importance of using mpH2MM to decouple FRET dynamics caused by conformational changes from photophysical transitions in confocal-based smFRET measurements of a DNA hairpin, the maltose binding protein, MalE, and the type-III secretion system effector, YopO, fromYersiniaspecies all exhibiting conformational dynamics ranging from the sub-second to microsecond timescales. Overall, we show that using mpH2MM facilitates the identification and quantification of biomolecular sub-populations and their origin.
NaCT (SLC13A5) facilitates citrate import and metabolism under nutrient-limited conditions
Authors: Kumar Avi , Cordes Thekla , Thalacker-Mercer Anna E. , Pajor Ana M. , Murphy Anne N. , Metallo Christian M.
Published: April 2021

Citrate lies at a critical node of metabolism linking tricarboxylic acid metabolism and fatty acid synthesis via acetyl-coenzyme A. Recent studies have linked the sodium citrate transporter (NaCT), encoded bySLC13A5, to dysregulated hepatic metabolism and pediatric epilepsy. To examine how NaCT-mediated citrate metabolism contributes to the pathophysiology of these diseases we applied13C isotope tracing toSLC13A5-deficient hepatocellular carcinoma (HCC) cell lines and primary rat cortical neurons. Exogenous citrate contributed to intermediary metabolism at appreciable levels only under hypoxic conditions. In the absence of glutamine, citrate supplementation increasedde novolipogenesis and growth of HCC cells. Knockout ofSLC13A5in Huh7 cells compromised citrate uptake and catabolism. Citrate supplementation rescued Huh7 cell viability in response to glutamine deprivation and Zn2+treatment, and these effects were mitigated by NaCT deficiency. Collectively, these findings demonstrate that NaCT-mediated citrate uptake is metabolically important under nutrient limited conditions and may facilitate resistance to metal toxicity.
Exploring zebrafish larvae as a COVID-19 model: probable SARS-COV-2 replication in the swim bladder
Authors: Laghi Valerio , Rezelj Veronica , Boucontet Laurent , Frétaud Maxence , Costa Bruno da , Boudinot Pierre , Salinas Irene , Lutfalla Georges , Vignuzzi Marco , Levraud Jean-Pierre
Published: April 2021

Animal models are essential to understand COVID-19 pathophysiology and for pre-clinical assessment of drugs and other therapeutic or prophylactic interventions. We explored the small, cheap and transparent zebrafish larva as a potential host for SARS-CoV-2. Bath exposure, as well as microinjection in the coelom, pericardium, brain ventricle, bloodstream, or yolk, did not result in detectable SARS-CoV-2 replication in wild-type larvae. However, when the virus was inoculated in the swim bladder, a modest increase in viral RNA was observed after 24 hours, suggesting a successful infection in some animals. This was confirmed by immunohistochemistry, with cells positive for SARS-CoV-2 nucleoprotein observed in the swim bladder. Several variants of concern were also tested with no evidence of increased infectivity in our model. Low infectivity of SARS-CoV-2 in zebrafish larvae was not due to the host type I interferon response, as comparable viral loads were detected in type I interferon-deficient animals. Mosaic overexpression of human ACE2 was not sufficient to increase SARS-CoV-2 infectivity in zebrafish embryos or in fish cells in vitro. In conclusion, wild-type zebrafish larvae appear mostly non-permissive to SARS-CoV-2, except in the swim bladder, an aerial organ sharing similarities with the mammalian lung.
Cell type and subcellular compartment specific APEX2 proximity labeling proteomics in the mouse brain
Authors: Dumrongprechachan V. , Soto G. , MacDonald M.L. , Kozorovitskiy Y.
Published: April 2021

The vertebrate brain consists of diverse neuronal types, classified by distinct anatomy and function, along with divergent transcriptomes and proteomes. Defining the cell type-specific neuroproteome is important for understanding the development and functional organization of neural circuits. This task remains challenging in complex tissue, due to suboptimal protein isolation techniques that often result in loss of cell-type specific information and incomplete capture of subcellular compartments. Here, we develop a genetically targeted proximity labeling approach to identify cell-type specific subcellular proteome in the mouse brain. Using adeno- associated viral transduction, we express subcellular-localized APEX2 to map the proteome of the nucleus, cytosol, and cell membrane of Drd1 receptor-positive striatal neurons. We show that each APEX2 construct can differentially and rapidly biotinylate proteinsin situacross various subcellular compartments, confirmed by imaging, electron microscopy, and mass spectrometry. This method enables flexible, cell-type specific quantitative profiling of subcellular proteome in the mouse brain.
Face dissimilarity judgements are predicted by representational distance in morphable and image-computable models
Authors: Jozwik Kamila M. , O’Keeffe Jonathan , Storrs Katherine R. , Guo Wenxuan , Golan Tal , Kriegeskorte Nikolaus
Published: April 2021

Human vision is attuned to the subtle differences between individual faces. Yet we lack a quantitative way of predicting how similar two face images look, or whether they appear to show the same person. Principal-components-based 3D morphable models are widely used to generate stimuli in face perception research. These models capture the distribution of real human faces in terms of dimensions of physical shape and texture. How well does a “face space” defined to model the distribution of faces as an isotropic Gaussian explain human face perception? We designed a behavioural task to collect dissimilarity and same/different identity judgements for 232 pairs of realistic faces. The stimuli densely sampled geometric relationships in a face space derived from principal components of 3D shape and texture (Basel Face Model, BFM). We then compared a wide range of models in their ability to predict the data, including the BFM from which faces were generated, a 2D morphable model derived from face photographs, and image-computable models of visual perception. Euclidean distance in the BFM explained both similarity and identity judgements surprisingly well. In a comparison against 14 alternative models, we found that BFM distance was competitive with representational distances in state-of-the-art image-computable deep neural networks (DNNs), including a novel DNN trained on BFM identities. Models describing the distribution of facial features across individuals are not only useful tools for stimulus generation. They also capture important information about how faces are perceived, suggesting that human face representations are tuned to the statistical distribution of faces.
Effects of learning and escitalopram administration on serum BDNF levels, a randomised placebo-controlled trial
Authors: Unterholzner J , Godbersen GM , Klöbl M , Ritter V , Pacher D , Seiger R , Varghese N , Eckert A , Lanzenberger R , Vanicek T
Published: April 2021

Background

The brain-derived neurotrophic factor (BDNF) has been implicated in processes essential for neuroplasticity. Learning and serotonin reuptake inhibitors (SSRI) foster neuronal reorganization, a mechanism potentially related to BDNF. This study aims to assess the effects of associative learning and escitalopram on serum BDNF (sBDNF) levels, to gain further knowledge on their dynamic interplay.

Methods

For three weeks, 37 participants performed one of two associative learning paradigms with either emotional or semantic content daily. During a subsequent three-week period of reversal learning, subjects either received escitalopram (10mg per day) or placebo. Before and after each learning period sBDNF values were assessed. Citalopram plasma levels were measured at the last time point. Linear mixed effects models (LME) and partial Spearman’s rank and Pearson correlations were used for statistical analyses.

Results

One-way LME resulted in a significant effect of time during the first learning period over both groups (p<0.01). Two-way LME revealed a significant interaction effect of the emotional content learning group and time (p=0.02). Three-way LME (time x reversal learning group x substance) showed no significant effects (all p> 0.05). Furthermore, correlation between citalopram and sBDNF level after three weeks of escitalopram administration exhibit a negative trend (partial Pearson correlation: r=-0.30, p=0.05; partial Spearman’s rank: r=-0.22, p=0.15).

Conclusion

The results suggest that three weeks of associative emotional content learning affect sBDNF levels, while subsequently assessed citalopram plasma and sBDNF levels tend to correlate negatively.

Key Points

Emotional learning may affect serum BDNF levels in healthy human subjects

Blood levels of citalopram and serum BDNF exhibit a negative correlation
Recursive MAGUS: scalable and accurate multiple sequence alignment
Authors: Smirnov Vladimir
Published: April 2021

Multiple sequence alignment tools struggle to keep pace with rapidly growing sequence data, as few methods can handle large datasets while maintaining alignment accuracy. We recently introduced MAGUS, a new state-of-the-art method for aligning large numbers of sequences. In this paper, we present a comprehensive set of enhancements that allow MAGUS to align vastly larger datasets with greater speed. We compare MAGUS to other leading alignment methods on datasets of up to one million sequences. Our results demonstrate the advantages of MAGUS over other alignment software in both accuracy and speed. MAGUS is freely available in open-source form athttps://github.com/vlasmirnov/MAGUS.
Vibrio choleraemay be transmitted to humans from bullfrog through food or water
Authors: Yang Yibin , Zhu Xia , Chen Yuhua , Liu Yongtao , Song Yi , Ai Xiaohui
Published: April 2021

Bullfrog is one of the most important economic aquatic animals in China. It is widely cultured in southern China, and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and even anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified asVibrio choleraeusing morphological, biochemical and 16S rRNA phylogenetic analysis. In this study,V. choleraewas isolated and identified from diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. At the same time, it was also found thatV. choleraemay be transmitted to humans from bullfrogs through bullfrog food and aquaculture water, creating a serious threat for human health. Therefore, society should pay attention to the modes of transmission ofVibrio choleraefrom bullfrog and formulate reasonable safety measures to avoid disasters.
The volatile cedrene from plant beneficialTrichoderma guizhouensemodulatesArabidopsisroot development through auxin transport and signaling
Authors: Li Yucong , Shao Jiahui , Fu Yansong , Chen Yu , Wang Hongzhe , Xu Zhihui , Feng Haichao , Xun Weibing , Liu Yunpeng , Zhang Nan , Shen Qirong , Xuan Wei , Zhang Ruifu
Published: April 2021

Rhizosphere microorganisms interact with plant roots by producing chemical signals to regulate root development. However, the involved distinct bioactive compounds and the signal transduction pathways are remaining to be identified. Here, we show that sesquiterpenes (SQTs) are the main volatile compounds produced by plant beneficialTrichoderma guizhouenseNJAU 4742, inhibition of SQTs synthesis in this strain indicated their involvement in plant-fungus cross-kingdom signaling. SQTs component analysis further identified the cedrene, a high abundant SQT in strain NJAU 4742, could stimulate plant growth and root development. Genetic analysis and auxin transport inhibition showed that auxin receptor TIR1, AFB2, auxin-responsive protein IAA14, and transcription factor ARF7, ARF19 affect the response of lateral roots to cedrene. Moreover, auxin influx carrier AUX1, efflux carrier PIN2 were also indispensable for cedrene-induced lateral root formation. Confocal imaging showed that cedrene affected the expression ofpPIN2:PIN2:GFPandpPIN3:PIN3:GFP, which may be related to the effect of cedrene on root morphology. These results suggest that a novel SQT molecule from plant beneficialT. guizhouensecan regulate plant root development through auxin transport and signaling.

One-sentence Summary

Cedrene, a high- abundance sesquiterpenes produced by plant beneficialTrichoderma guizhouenseNJAU 4742, stimulatesArabidopsislateral root formation and primary root elongation by relying on auxin signaling pathway and auxin transporter PIN2 and AUX1.
Isolation and characterization of a novel bacteriophage, Kapi1, capable of O-antigen modification in commensalEscherichia coli
Authors: Pick Kat , Raivio Tracy
Published: April 2021

In this study, we describe the isolation and characterization of novel bacteriophage Kapi1 (vB_EcoP_Kapi1) isolated from a strain of commensalEscherichia coliinhabiting the gastrointestinal tract of healthy mice. We show that Kapi1 is a temperate phage integrated into tRNAargWof strain MP1 and describe its genome annotation and structure. Kapi1 shows limited homology to other characterized prophages but is most similar to the phages ofShigella flexneri, and clusters taxonomically with P22-like phages. Investigation of the lifestyle of Kapi1 shows that this phage displays unstable lysogeny and influences the growth of its host. The receptor for Kapi1 is the lipopolysaccharide O-antigen, and we further show that Kapi1 alters the structure of its hosts O-antigen in multiple ways. We hope to use MP1 and Kapi1 as a model system to explore molecular mechanisms of mammalian colonization byE. coliand ask what the role(s) of prophages in this context might be.

Importance

Although research exploring the microbiome has exploded in recent years, our understanding of the viral component of the microbiome is lagging far behind our understanding of the bacterial component. The vast majority of intestinal bacteria carry prophages integrated into their chromosomes, but most of these bacteriophages remain uncharacterized and unexplored. Here, we isolate and characterize a novel temperate bacteriophage infecting a commensal strain ofEscherichia coli.We aim to explore the interactions between bacteriophages and their hosts in the context of the gastrointestinal tract, asking what role(s) temperate bacteriophage may play in growth and survival of bacteria in the gastrointestinal tract. Understanding the fundamental biology of commensal bacteria in the gastrointestinal tract can inform the development of novel antimicrobial or probiotic strategies for intestinal infections.
The role of Education 5.0 in accelerating the implementation of SDGs and challenges encountered at the University of Zimbabwe
Authors: Togo Muchaiteyi , Gandidzanwa Crecentia Pamidzai
Published: April 2021

Purpose

Higher education can play a role in the implementation of sustainable development goals (SDGs). However, there are steps and structures which are necessary for this to be possible. This paper aims to establish how the University of Zimbabwe (UZ)’s innovation hub is implementing SDGs for water, energy and food, resources which are in critical shortage in Harare; as part of its mandate to implement the newly introduced Education 5.0.

Design/methodology/approach

This paper is based on qualitative research. Interview guides were used to gather information from Harare residents, university staff and students. Observations were undertaken and review of secondary data was done. The data was collated into a narrative and content analysis was used to analyse it.

Findings

The UZ innovation hub is aimed to deliver Education 5.0. It houses research projects on energy and food. Water-related projects are still in the pipeline. The research revealed challenges that call for mobilisation of funding to support the projects, to protect researchers’ intellectual property rights and to strengthen interdisciplinary research and information flows between the university and the community. The paper argues for higher and tertiary education institutions to work directly with policymakers and societies in implementing SDGs.

Originality/value

Education 5.0 is relatively new and not much research has been done to establish how it intends to deliver its objectives. The innovation hub model has the potential to yield positive results in SDGs implementation. This research can motivate other universities to work with policymakers and communities in implementing SDGs for urban transformative adaptation.
Cross-disciplinary issues in international marketing: a systematic literature review on international marketing and ethical issues
Authors: Chatterjee Sheshadri , Chaudhuri Sumana , Sakka Georgia , Apoorva
Published: April 2021

Purpose

The purpose of this paper is to discuss the evolution of the cross-disciplinary area of ethics and international marketing and to highlight the current and future scope of research in this area.

Design/methodology/approach

The authors conducted a systematic literature review (SLR) of research papers from reputed journals which publish articles in this cross-disciplinary subject area. This paper especially investigates the perception, issues, concepts and theories used in ethics and international marketing. Scopus and Web of Science databases were primarily used to select the articles.

Findings

The paper highlights the importance of cross-disciplinary research in the areas of ethics and international marketing. The study also shows different kinds of research work published in this area between 1994 and 2020. Also, the study shows that the maximum research has been conducted in the USA and the UK. Finally, the paper also highlights the major theories that different authors have used in this interdisciplinary area.

Research limitations/implications

The paper does not discuss other complex areas of cross-disciplinary international marketing other than ethics and international marketing. The paper omits the literature from books, stand-alone nonindexed journals, etc. Also, the paper has only used the Web of Science and Scopus databases.

Practical implications

The study argues the importance of ethics in international marketing. The study also provides inputs to the international marketers so that they can successfully address the complex challenges in the cross-disciplinary area of ethics and international marketing. The study also helps marketers to rethink their approaches on international marketing ethics.

Originality/value

This may be one of the few studies in the cross-disciplinary area of ethics and international marketing. This paper can open avenues and influence other researchers to study the cross-disciplinary areas of marketing.
Employees' task performance and propensity to take charge: the role of LMX and leader's task orientation
Authors: Ahmed Ishfaq , Afzal Rabia , Abdul Rasid Siti Zaleha
Published: April 2021

Purpose

Recent literature has focused on the outcomes associated with employee performance, but how and when it leads to work-related outcomes further is an area that has not gained due attention. Against this backdrop, this study entails investigating the effects of employee performance on their taking-charge behavior through the mediation of leader–member exchange (LMX) and the leader's task-oriented behavior's moderating role.

Design/methodology/approach

Using a questionnaire-based survey design, the study is based on a sample of 304 employees of pharmaceutical companies' sales departments. The two-stage lag approach has been used for data collection, where leader–follower dyads participated in the study.

Findings

The study's findings reveal that better-performing employees are considered in-group members by their leaders, and the presence of high LMX makes employees reciprocate by adopting charge behavior. Furthermore, a leader's task-oriented behavior fosters the performance – LMX and performance – taking charge relationship mediated through LMX, a moderated mediation mechanism exists.

Originality/value

The study offers a novel explanation by considering employee performance as a predictor instead of an outcome variable. Furthermore, recent literature has considered adverse outcomes of performance, while this study considers the positive aspects of employee performance (i.e. LMX and charge behavior). It also offers the role of both employee- and leader-specific factors in determining the LMX relationship.
Governmental customer concentration and audit pricing
Authors: Chen Hanmei , Jia Weishi , Li Shuo , Liu Zenghui
Published: April 2021

Purpose

The purpose of this paper is to examine how the concentration of a specific customer type – governmental customer, affects the pricing of audit services in the USA.

Design/methodology/approach

This paper applies a standard audit pricing model by regressing audit fees on governmental customer concentration and other common determinants of audit fees. This paper also adopts an instrumental variable approach and performs propensity-score matched sample analyzes to mitigate the potential endogeneity problem.

Findings

Using data from major customer disclosures of US publicly listed firms from 2000 to 2014, this paper finds that governmental customer concentration is positively associated with audit fees, suggesting that a higher level of governmental customer concentration increases a firm’s audit risks and audit effort. In addition, this paper performs cross-sectional analyzes and show that the association between governmental customer concentration and audit fees is more pronounced for firms with weak internal governance, weak external monitoring and high financial risks.

Originality/value

This paper furthers the understanding of the interactive relationships in supply chain systems and adds new evidence to the literature on customer concentration. Prior studies on customer concentration typically treat all customer types in a uniform manner. To the knowledge, this is the first study that separates governmental customers from other types of customers in an audit pricing setting. The findings highlight the importance of examining governmental customer concentration when assessing a firm’s audit risks and audit fees.