bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple and easily implemented risk model to predict 1-year ischemic stroke and systemic embolism in Chinese patients with atrial fibrillation
Authors: Jiang Chao , Chen Tian-Ge , Du Xin , Li Xiang , He Liu , Lai Yi-Wei , Xia Shi-Jun , Liu Rong , Hu Yi-Ying , Li Ying-Xue , Jiang Chen-Xi , Liu Nian , Tang Ri-Bo , Bai Rong , Sang Cai-Hua , Long De-Yong , Xie Guo-Tong , Dong Jian-Zeng , Ma Chang-Sheng
Published: May 2021

Background:

Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.

Methods:

From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA2DS2-VA score (excluding female sex from the CHA2DS2-VASc score).

Results:

Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%–1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65–0.73), higher than that of CHA2DS2-VA score (0.66, 95% CI: 0.62–0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA2DS2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%–15.7%).

Conclusion:

In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA2DS2-VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making.

Trial Registration:

www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).
Targeted Muscle Reinnervation in Partial Hand Amputations
Authors: Wimalawansa Sunishka M. , Lygrisse Daniel , Anderson Spencer R. , Eberlin Kyle R. , Westenberg Ritsaart , Schulz Steven , West Julie , Valerio Ian L.
Published: May 2021

Targeted muscle reinnervation (TMR) surgery has been shown to aid in prevention and treatment of neuropathic pain. Technical and anatomical descriptions of TMR surgery for upper extremity amputees (including transradial, transhumeral, and forequarter amputations) have been reported, yet such descriptions of TMR surgery for partial hand amputations are currently lacking. Herein we outline the technique of different types of partial hand amputation TMR surgeries to serve as a reference and guide. A retrospective review was performed by our multi-institutional team to identify clinical cases where partial hand TMR surgeries were performed. Patient demographics, characteristics, amputation subtype, nerve transfer, pain score, pain outcome, and functional outcome data were collected and analyzed. From January 2018 to September 2019, 13 patients underwent partial hand TMR procedures. Eight cases resulted from trauma, and 6 were secondary to oncologic procedures. The amputations consisted of 8 ray, 2 trans-metacarpal, 2 radial-sided hand, and 1 index finger amputation with recurrent painful neuromas. Twelve patients were weaned off narcotics completely and only 3 remained on a neuromodulator for ongoing pain control. Technical considerations for partial hand TMR surgery have been outlined, with early pilot data showing beneficial pain control outcomes.
Factors That Influence Infant Immunity and Vaccine Responses
Authors: Zimmermann Petra , Jones Christine E.
Published: May 2021

The neonatal period and early infancy are times of increased vulnerability to infection. The immune system of infants undergoes rapid changes and a number of factors can influence the maturation and function of the early infant immune system, amongst these factors are maternal infections and immunity. Infants who are HIV-exposed, but uninfected show important immune alterations, which are likely to be associated with the increased morbidity and mortality observed in these infants. Maternally derived antibodies are crucial in early life to protect infants from infection during the time when their own immune system is becoming more experienced and fully mature. However, maternal antibodies can also interfere with the infant’s own antibody responses to primary vaccination. Preterm infants are particularly vulnerable to infection, having not had the opportunity to benefit from the transplacental transfer of maternal antibodies in late pregnancy. In addition, further differences have been observed in the innate and adaptive immune system between preterm and term infants. Here, we focus on maternal influences on the infant immune system, using HIV and maternal vaccination as examples and finish by considering how prematurity impacts infant immune responses to vaccination.
The time is now: antimicrobial stewardship in solid organ transplantation
Authors: Hand Jonathan M.
Published: May 2021

Purpose of review

To provide a summary of complications of antimicrobials and opportunities for antimicrobial stewardship (AS) in solid organ transplant (SOT) patient care.

Recent findings

Personalized, precision antimicrobial prescribing in SOT aiming to avoid negative consequences of antimicrobials is essential to improving patient outcomes. The positive impact AS efforts in transplant care has been recognized and bespoke activities tailored to special interests of transplant patients and providers are evolving. Strategies to optimize stewardship interventions targeting antibacterial, antiviral, and antifungal drug selection and dosing in the transplant population have been recently published though clinical integration using a ‘handshake’ stewardship model is an optimal starting point in transplant care. Other recent studies involving transplant recipients have identified opportunities to shorten duration or avoid antimicrobials for certain commonly encountered clinical syndromes. This literature, informing recent consensus clinical practice guidelines, may help support institutional practice guidelines and protocols. Proposals to track and report stewardship process and outcome measures as a routine facet of programmatic transplant quality reporting have been published. However, developing novel metrics accounting for nuances of transplant patients and programs is critical. Important studies are needed to evaluate organizational transplant prescribing cultures and optimal behavioral science-based interventions relevant to antimicrobial use in this population.

Consequences of antimicrobial use, such as drug toxicities, and Clostridiodes difficile (CDI) and multidrug-resistant organisms colonization and infection disproportionately affect SOT recipients and are associated with poor allograft and patient outcomes. Stewardship programs encompassing transplant patients aim to personalize antimicrobial prescribing and optimize outcomes. Further studies are needed to better understand optimal intervention strategies in SOT.
Recurrent glomerulonephritis after kidney transplantation: a practical approach
Authors: De Souza Laura , Prunster Janelle , Chan Doris , Chakera Aron , Lim Wai H.
Published: May 2021

Purpose of review

This review will provide a practical approach in the assessment of kidney failure patients with primary glomerulonephritides (GN) being considered for kidney transplantation, focusing on high-risk subtypes of immunoglobulin A nephropathy, focal segmental glomerulosclerosis, idiopathic membranous glomerulonephritis and membranoproliferative glomerulonephritis.

Recent findings

Recurrent glomerulonephritis remains one of the most common causes of allograft loss in kidney transplant recipients. Although the epidemiology and clinical outcomes of glomerulonephritis recurrence occurring after kidney transplantation are relatively well-described, the natural course and optimal treatment strategies of recurrent disease in kidney allografts remain poorly defined. With a greater understanding of the pathophysiology and treatment responses of patients with glomerulonephritis affecting the native kidneys, these discoveries have laid the framework for the potential to improve the management of patients with high-risk glomerulonephritis subtypes being considered for kidney transplantation.

Advances in the understanding of the underlying immunopathogenesis of primary GN has the potential to offer novel therapeutic options for kidney patients who develop recurrent disease after kidney transplantation. To test the efficacy of novel treatment options in adequately powered clinical trials requires a more detailed understanding of the clinical and histological characteristics of kidney transplant recipients with recurrent glomerulonephritis.
Regulation of host and viral promoters during human cytomegalovirus latency via US28 and CTCF
Authors: Elder Elizabeth G. , Krishna Benjamin A. , Poole Emma , Perera Marianne , Sinclair John
Published: May 2021

Viral latency is an active process during which the host cell environment is optimized for latent carriage and reactivation. This requires control of both viral and host gene promoters and enhancers often at the level of chromatin, and several viruses co-opt the chromatin organiser CTCF to control gene expression during latency. While CTCF has a role in the latencies of alpha- and gamma-herpesviruses, it was not known whether CTCF played a role in the latency of the beta-herpesvirus human cytomegalovirus (HCMV). Here, we show that HCMV latency is associated with increased CTCF expression and CTCF binding to the viral major lytic promoter, the major immediate early promoter (MIEP). This increase in CTCF binding is dependent on the virally encoded G protein coupled receptor, US28, and contributes to suppression of MIEP-driven transcription, a hallmark of latency. Furthermore, we show that latency-associated upregulation of CTCF represses expression of the neutrophil chemoattractants S100A8 and S100A9 which we have previously shown are downregulated during HCMV latency. As with downregulation of the MIEP, CTCF binding to the enhancer region of S100A8/A9 drives their suppression, again in a US28-dependent manner. Taken together, we identify CTCF upregulation as an important mechanism for optimizing latent carriage of HCMV at both the levels of viral and cellular gene expression.
Unified platform for genetic and serological detection of COVID-19 with single-molecule technology
Authors: Furth Noa , Shilo Shay , Cohen Niv , Erez Nir , Fedyuk Vadim , Schrager Alexander M. , Weinberger Adina , Dror Amiel A. , Zigron Asaf , Shehadeh Mona , Sela Eyal , Srouji Samer , Amit Sharon , Levy Itzchak , Segal Eran , Dahan Rony , Jones Dan , Douek Daniel C. , Shema Efrat
Published: May 2021

The COVID-19 pandemic raises the need for diverse diagnostic approaches to rapidly detect different stages of viral infection. The flexible and quantitative nature of single-molecule imaging technology renders it optimal for development of new diagnostic tools. Here we present a proof-of-concept for a single-molecule based, enzyme-free assay for detection of SARS-CoV-2. The unified platform we developed allows direct detection of the viral genetic material from patients’ samples, as well as their immune response consisting of IgG and IgM antibodies. Thus, it establishes a platform for diagnostics of COVID-19, which could also be adjusted to diagnose additional pathogens.
Comparative transcriptome analysis of noble crayfish and marbled crayfish immune response to Aphanomyces astaci challenges
Authors: Boštjančić Ljudevit Luka , Francesconi Caterina , Rutz Christelle , Hoffbeck Lucien , Poidevin Laetitia , Kress Arnaud , Jussila Japo , Makkonen Jenny , Feldmeyer Barbara , Bálint Miklós , Lecompte Odile , Theissinger Kathrin
Published: May 2021

Introduction of invasive North American crayfish species and their pathogen Aphanomyces astaci has significantly contributed to the decline of European freshwater crayfish populations. In this study, noble crayfish, a susceptible native European species, and marbled crayfish, an invasive disease-resistant species, were challenged with haplogroup A (low virulence) and haplogroup B (high virulence) strain of A. astaci. Hepatopancreatic tissue was isolated 3 and 21 days post-challenge. Our results revealed strong up-regulation in expression levels of the prophenoloxidase cascade immune-related genes in the haplogroup B challenged noble crayfish 3 days post-challenge. In the marbled crayfish, we observed an up-regulation of immune system relevant genes (DSCAM, AP, ALFs, CTLs and hemocyanin) 3 days post-challenge. This response highlights the marbled crayfish capability of building the immune tolerance. Furthermore, we successfully characterised several novel immune related gene groups in both crayfish species, contributing to our current understanding of crayfish immune related genes landscape.

Graphical abstract

a) Study species noble crayfish (Astacus astacus) in purple and marbled crayfish (Procambarus virginalis) in green challenged with the pathogen Aphanomyces astaci haplogroup A (Hap A) strain of low virulence and haplogroup B (Hap B) strain of high virulence. b) Sampling scheme of the infection experiment: 5 individuals were taken from the experiment three- and 21-days post-challenge. From each individual, a hepatopancreas sample was taken, followed by RNA isolation and sequencing. c)De novo transcriptome assembly and annotation were conducted for each species. d) Differential gene expression analysis revealed the distinct immune response in the noble crayfish 3 days post-challenge with the Hap B strain of A. astaci and marbled crayfish 3 days post-challenge with the Hap A strain of A. astaci. Immune related DEGs were not present in either species 21 days post-challenge with A. astaci.e) Noble crayfish challenged with the Hap B strain of A. astaci were acutely infected and ultimately moribund, while the A. astaci Hap A challenged marbled crayfish showed high resistance to the pathogen, resulting infected without any mortality.
Dysregulated heparan sulfate proteoglycan metabolism promotes Ewing sarcoma tumor growth
Authors: Vasileva Elena , Warren Mikako , Triche Timothy J. , Amatruda James F.
Published: May 2021

The Ewing sarcoma family of tumors is a group of malignant small round blue cell tumors (SRBCTs) that affects children, adolescents and young adults. The tumors are characterized by reciprocal chromosomal translocations that generate chimeric fusion oncogenes, the most common of which is EWSR1-FLI1. Survival is extremely poor for patients with metastatic or relapsed disease, and no molecularly-targeted therapy for this disease currently exists. The absence of a reliable genetic animal model of Ewing sarcoma has impaired investigation of tumor cell/microenvironmental interactions in vivo. We have developed a new genetic model of Ewing sarcoma based on Cre-inducible expression of human EWSR1-FLI1 in wild type zebrafish, which causes rapid onset of SRBCTs at high penetrance. The tumors express canonical EWSR1-FLI1 target genes and stain for known Ewing sarcoma markers including CD99. Growth of tumors is associated with activation of the MAPK/ERK pathway, which we link to dysregulated extracellular matrix metabolism in general and heparan sulfate catabolism in particular. Targeting heparan sulfate proteoglycans with the specific heparan sulfate antagonist Surfen reduces ERK1/2 signaling and decreases tumorigenicity of Ewing sarcoma cells in vitro and in vivo. These results highlight the important role of the extracellular matrix in Ewing sarcoma tumor growth and the potential of agents targeting proteoglycan metabolism as novel therapies for this disease.
Linking the brain with behaviour: the neural dynamics of success and failure in goal-directed behaviour
Authors: Robinson Amanda K. , Rich Anina N. , Woolgar Alexandra
Published: May 2021

The human brain is extremely flexible and capable of rapidly selecting relevant information in accordance with task goals. Regions of frontoparietal cortex flexibly represent relevant task information such as task rules and stimulus features when participants perform tasks successfully, but less is known about how information processing breaks down when participants make mistakes. This is important for understanding whether and when information coding recorded with neuroimaging is directly meaningful for behaviour. Here, we used magnetoencephalography (MEG) to assess the temporal dynamics of information processing, and linked neural responses with goal-directed behaviour by analysing how they changed on behavioural error. Participants performed a difficult stimulus-response task using two stimulus-response mapping rules. We used time-resolved multivariate pattern analysis to characterise the progression of information coding from perceptual information about the stimulus, cue and rule coding, and finally, motor response. Response-aligned analyses revealed a ramping up of perceptual information prior to a correct response, suggestive of internal evidence accumulation. Strikingly, when participants made a stimulus-related error, and not when they made other types of errors, patterns of activity initially reflected the stimulus presented, but later reversed, and accumulated towards a representation of theincorrectstimulus. This suggests that the patterns recorded at later timepoints reflect an internally generated stimulus representation that was used to make the (incorrect) decision.

These results illustrate the orderly and overlapping temporal dynamics of information coding in perceptual decision-making and show a clear link between neural patterns in the late stages of processing and behaviour.
Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies
Authors: Elhakeem Ahmed , Hughes Rachael A. , Tilling Kate M. , Cousminer Diana L. , Jackowski Stefan A. , Cole Tim J. , Kwong Alex S.F. , Li Zheyuan , Grant Struan F.A. , Baxter-Jones Adam D.G. , Zemel Babette S. , Lawlor Deborah A.
Published: May 2021

Longitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. This paper provides a guide to describing nonlinear growth trajectories for repeatedly measured continuous outcomes using linear mixed-effects (LME) models with linear splines and natural cubic splines, nonlinear mixed effects Super Imposition by Translation and Rotation (SITAR) models, and latent trajectory models. The underlying model for each of the four approaches, the similarities and differences between models, and their advantages and disadvantages are described. Their applications and correct interpretation are illustrated by analysing repeated bone mass measures across three cohort studies with 8,500 individuals and 37,000 measurements covering ages 5-40 years. Linear and natural cubic spline LME models and SITAR provided similar descriptions of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Latent trajectory models identified up to four subgroups of individuals with distinct trajectories during adolescence and similar trajectories in childhood and adulthood. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts. In summary, we present a resource for characterising nonlinear longitudinal growth trajectories, that could be adapted for other complex traits. Scripts and synthetic datasets are provided so readers can replicate trajectory modelling and visualisation using the open-source R software.
Identification of bipotent progenitors that give rise to myogenic and connective tissues in mouse
Authors: Grimaldi Alexandre , Comai Glenda , Mella Sébastien , Tajbakhsh Shahragim
Published: May 2021

How distinct cell fates are manifested by direct lineage ancestry from bipotent progenitors, or by specification of individual cell types within a field of cells is a key question for understanding the emergence of tissues. The interplay between skeletal muscle progenitors and associated connective tissues cells provides a model for examining how muscle functional units are established. Most craniofacial structures originate from the vertebrate-specific neural crest cells except in the dorsal portion of the head, where they arise from cranial mesoderm. Here, using multiple lineage-traced single cell RNAseq, advanced computational methods and in situ analyses, we identify Myf5+bipotent progenitors that give rise to both muscle and juxtaposed connective tissue. Following this bifurcation, muscle and connective tissue cells retain complementary signalling features and maintain spatial proximity. Interruption of upstream myogenic identity shifts muscle progenitors to a connective tissue fate. Interestingly, Myf5-derived connective tissue cells, which adopt a novel regulatory signature, were not observed in ventral craniofacial structures that are colonised by neural crest cells. Therefore, we propose that an ancestral program gives rise to bifated muscle and connective tissue cells in skeletal muscles that are deprived of neural crest.
A new twist in ABC transporter mediated multidrug resistance – Pdr5 is a drug/proton co-transporter
Authors: Wagner Manuel , Blum Daniel , Raschka Stefanie L. , Nentwig Lea-Marie , Gertzen Christoph G. W. , Chen Minghao , Gatsogiannis Christos , Harris Andrzej , Smits Sander H. J. , Wagner Richard , Schmitt Lutz
Published: May 2021

The two major efflux pump systems are involved in multidrug resistance (MDR): (i) ATP binding cassette (ABC) transporters and (ii) secondary transporters. While the former use binding and hydrolysis of ATP to facilitate export of cytotoxic compounds, the latter utilize electrochemical gradients to expel their substrates. Pdr5 from Saccharomyces cerevisiae is a prominent member of eukaryotic ABC transporters that are involved in MDR and used as a frequently studied model system. Although investigated for decades, the underlying molecular mechanisms of transport and specificity remain elusive. Here, we provide electrophysiological data on reconstituted Pdr5 demonstrating that this MDR efflux pump does not only actively translocate its substrates across the lipid bilayer, but generates a proton motif force in the presence of Mg2+-ATP and substrates by acting as a proton/drug co-transporter. Importantly, a strictly substrate dependent co-transport of protons was also observed in in vitro transport studies using Pdr5-enriched plasma membranes. Similar observations have not yet been reported for any other MDR efflux pump. We conclude from these results that the mechanism of MDR conferred by Pdr5 and likely other transporters is more complex than the sole extrusion of cytotoxic compounds and involves secondary coupled processes suitable to increase the effectiveness.
Construction of redesigned pMAL expression vector for easy and fast purification of active native antimicrobial peptides
Authors: Gardijan Lazar , Miljkovic Marija , Obradovic Mina , Borovic Branka , Vukotic Goran , Jovanovic Goran , Kojic Milan
Published: May 2021

Many protein expression and purification systems are commercially available to provide a sufficient amount of pure, soluble and active native protein, such as the pMAL system based onE. colimaltose binding protein tag (MBP). Adding specific amino acid tags to the N- or C-terminus of the protein increases solubility and facilitates affinity purification of proteins. However, many of expressed tagged proteins consequently lose functionality, particularly small peptides such as antimicrobial peptides (AMPs). Objective of this study was to redesign the pMAL expression vector in order to increase the efficacy of MBP tag separation from native peptides. Redesign of the pMAL expression vector included introduction of the His6tag and the enterokinase cleavage site downstream from the original MBP tag and Xa cleavage site enabling purification of native and active peptide (P) following two-step affinity chromatography. In the first step the entire MBP-His6-P fusion protein is purified through binding to Ni-NTA agarose. In the second step, the purification was performed by adding mixture of amylose and Ni-NTA agarose resins following cleavage of the fusion protein with active His6tagged enterokinase. This removes MBP-His6and His6-enterokinase leaving pure native protein in solution. The redesigned pMAL vectors were optimized for cytoplasmic (pMALc5HisEk) and periplasmic (pMALp5HisEk) peptides expression. Two-step purification protocol was successfully applied in purification of active native AMPs, lactococcin A and human β-defensin. Taken together, we established the optimal conditions and pipeline for overexpression and purification of large amount of native peptides, that can be implemented in any laboratory.
ERK1/2 is an ancestral organising signal in spiral cleavage
Authors: Seudre Océane , Carrillo-Baltodano Allan M. , Liang Yan , Martín-Durán José M.
Published: May 2021

Animal development is classified as conditional or autonomous based on whether cell fates are specified through inductive signals or maternal determinants, respectively. Yet how these two major developmental modes evolved remains unclear. During spiral cleavage—a stereotypic embryogenesis ancestral to 15 invertebrate groups, including molluscs and annelids—most lineages specify cell fates conditionally, while some define the primary axial fates autonomously. To identify the mechanisms driving this change, we studiedOwenia fusiformis, an early-branching, conditional annelid. InOwenia, ERK1/2-mediated FGF receptor signalling specifies the endomesodermal progenitor. This cell likely acts as an organiser, inducing mesodermal and posterodorsal fates in neighbouring cells and repressing anteriorising signals. The organising role of ERK1/2 inOweniais shared with molluscs, but not with autonomous annelids. Together, these findings suggest that conditional specification of an ERK1/2+embryonic organiser is ancestral in spiral cleavage and was repeatedly lost in annelid lineages with autonomous development.
Effective prophylaxis of COVID-19 in rhesus macaques using a combination of two parentally-administered SARS-CoV-2 neutralizing antibodies
Authors: Beddingfield Brandon J. , Maness Nicholas J. , Fears Alyssa C. , Rappaport Jay , Aye Pyone Pyone , Russell-Lodrigue Kasi , Doyle-Meyers Lara A. , Blair Robert V. , Carias Ann M. , Madden Patrick J. , Redondo Ramon Lorenzo , Gao HongMei , Montefiori David , Hope Thomas J. , Roy Chad J.
Published: May 2021

SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.
A new method to study genome mutations using the information entropy
Authors: Vopson Melvin M. , Robson Samuel C.
Published: May 2021

We report a non-clinical, mathematical method of studying genetic sequences based on the information theory. Our method involves calculating the information entropy spectrum of genomes by splitting them into “windows” containing a fixed number of nucleotides. The information entropy value of each window is computed using the m-block information entropy formula. We show that the information entropy spectrum of genomes contains sufficient information to allow detection of genetic mutations, as well as possibly predicting future ones. Our study indicates that the best m-block size is 2 and the optimal window size should contain more than 9, and less than 33 nucleotides. In order to implement the proposed technique, we created specialized software, which is freely available. Here we report the successful test of this method on the reference RNA sequence of the SARS-CoV-2 virus collected in Wuhan, Dec. 2019 (MN908947) and one of its randomly selected variants from Taiwan, Feb. 2020 (MT370518), displaying 7 mutations.
TCAB1 prevents nucleolar accumulation of the telomerase RNA to promote telomerase assembly
Authors: Klump Basma M. , Perez Gloria I. , Patrick Eric M. , Adams-Boone Kate , Cohen Scott B. , Han Li , Yu Kefei , Schmidt Jens C.
Published: May 2021

Localization of a wide variety of RNAs to non-membrane bound cellular compartments such as nucleoli, Cajal bodies, and stress-granules is critical for their function and stability. The molecular mechanisms that underly the recruitment and exclusion of specific RNAs from these phase-separated organelles is incompletely understood. Telomerase is a ribonucleoprotein (RNP) that is composed of the reverse transcriptase protein TERT, the telomerase RNA (TR), and several auxiliary proteins that associate with TR, including TCAB1. Here we show that in the absence of TCAB1, TR is tightly bound to the nucleolus, while TERT localizes to the nucleoplasm and is largely excluded from the nucleolus, significantly reducing telomerase assembly. Thus, nuclear compartmentalization by the non-membrane bound nucleolus counteracts telomerase assembly and TCAB1 is required to exclude the telomerase RNA from the nucleolus. Our work provides insight into the mechanism and functional consequences of RNA recruitment to organelles formed by phase separation proposes a new model explaining the critical role of TCAB1 in telomerase function.
Polyelectrolyte Coating of Ferumoxytol Differentially Impacts on Labeling of Inflammatory and Steady-State Dendritic Cell Subtypes
Authors: Celikkin Nehar , Wong John E. , Zenke Martin , Hieronymus Thomas
Published: May 2021

Engineered magnetic nanoparticles (MNPs) are emerging as advanced tools for medical applications. The coating of MNPs using polyelectrolytes (PEs) is a versatile means to tailor MNP properties and is used to optimize MNP functionality. Dendritic cells (DCs) are critical regulators of adaptive immune responses. Functional distinct DC subsets exist either under steady-state or inflammatory conditions, which are explored for the specific treatment of various diseases, such as cancer, autoimmunity or transplant rejection. Here, the impact of PE coating of ferumoxytol for uptake into both inflammatory and steady-state DCs and cellular responses to the MNP labeling is addressed. Labeling efficiency by uncoated and PE-coated ferumoxytol is highly variable in different DC subsets, and PE coating significantly improves the labeling of steady-state DCs. Uncoated ferumoxytol results in increased cytotoxicity of steady-state DCs after labeling that is abolished by the PE coating, while no increased cell death is observed in inflammatory DCs. Furthermore, uncoated and PE-coated ferumoxytol appears immunologically inert in inflammatory DCs but induces activation of steady-state DCs. These results show that PE coating of MNPs can be applied to endow particles with desired properties for enhanced uptake and cell type-specific responses in distinct target DC populations.
Fur4 mediated uracil-scavenging to screen for surface protein regulators
Authors: Paine Katherine M. , Ecclestone Gabrielle B. , MacDonald Chris
Published: May 2021

Cell surface membrane proteins perform diverse and critical functions and are spatially and temporally regulated by membrane trafficking pathways. Although perturbations in these pathways underlie many pathologies, our understanding of these pathways at a mechanistic level remains incomplete. Using yeast as a model, we have developed an assay that reports on the surface activity of the Fur4 uracil permease in uracil auxotroph strains grown in the presence of limited uracil. This assay was used to screen a haploid deletion library that identified mutants with both diminished and enhanced comparative growth in restricted uracil media. Factors identified, including various multi-subunit complexes, were enriched for membrane trafficking and transcriptional functions, in addition to various uncharacterised genes. Bioinformatic analysis of expression profiles from many strains lacking identified transcription factors required for efficient uracil-scavenging revealed they control expression of other uracil-scavenging factors, in addition to membrane trafficking genes essential for viability, and therefore not represented in the screen. Finally, we performed a secondary mating factor secretion screen to functionally categorise factors implicated in uracil-scavenging, most of which are conserved throughout evolution.
Conserved noncoding sequences provide insights into regulatory sequence and loss of gene expression in maize
Authors: Song Baoxing , Buckler Edward S. , Wang Hai , Wu Yaoyao , Rees Evan , Kellogg Elizabeth A. , Gates Daniel J. , Khaipho-Burch Merritt , Bradbury Peter J. , Ross-Ibarra Jeffrey , Hufford Matthew B. , Romay M. Cinta
Published: May 2021

Thousands of species will be sequenced in the next few years; however, understanding how their genomes work, without an unlimited budget, requires both molecular and novel evolutionary approaches. We developed a sensitive sequence alignment pipeline to identify conserved noncoding sequences (CNSs) in the Andropogoneae tribe (multiple crop species descended from a common ancestor ∼18 million years ago). The Andropogoneae share similar physiology while being tremendously genomically diverse, harboring a broad range of ploidy levels, structural variation, and transposons. These contribute to the potential of Andropogoneae as a powerful system for studying CNSs and are factors we leverage to understand the function of maize CNSs. We found that 86% of CNSs were comprised of annotated features, including introns, UTRs, putative cis-regulatory elements, chromatin loop anchors, noncoding RNA (ncRNA) genes, and several transposable element superfamilies. CNSs were enriched in active regions of DNA replication in the early S phase of the mitotic cell cycle and showed different DNA methylation ratios compared to the genome-wide background. More than half of putative cis-regulatory sequences (identified via other methods) overlapped with CNSs detected in this study. Variants in CNSs were associated with gene expression levels, and CNS absence contributed to loss of gene expression. Furthermore, the evolution of CNSs was associated with the functional diversification of duplicated genes in the context of maize subgenomes. Our results provide a quantitative understanding of the molecular processes governing the evolution of CNSs in maize.
The longitudinal association between soybean and non-soybean legumes intakes and risk of cardiovascular disease: Isfahan cohort study
Authors: Nouri Fatemeh , Haghighatdoost Fahimeh , Mohammadifard Noushin , Mansourian Marjan , Sadeghi Masoumeh , Roohafza Hamidreza , Khani Azam , Sarrafzadegan Nizal
Published: May 2021

Purpose

The associations between legume consumption and cardiovascular events (CVEs) have extensively been studied. However, there are few studies that considered longitudinal association between legume consumption (with repeated measurements across time) and CVEs in low-income countries where legume consumption is lower than the Western countries. The authors aimed to investigate the long-term longitudinal relationship between soybean, non-soybean and overall legume consumption and CVEs using repeated measures of legumes and time-varying confounders in a cohort study of the general population.

Design/methodology/approach

The current study was performed within the framework of the Isfahan cohort study among 5,432 healthy participants. The participants were followed-up for fatal and non-fatal myocardial infarction, unstable angina, fatal and non-fatal stroke and sudden cardiac death for 13 years. Dietary intake was evaluated using a validated food frequency questionnaire in 2001, 2007 and 2013. The hazard ratios (HRs) and 95% confidence intervals (CI) for CVEs between categories of soybean, non-soybean and overall legumes intake were examined using marginal Cox's regression analysis.

Findings

Long-term consumptions of overall legumes more than three times per week and non-soybean three times or more per week compared with those who had less than once a week were associated with 19.5% (HR = 0.805, 95% CI: 0.650,0.998; p < 0.048) and a 18.5% (HR = 0.815, 95% CI: 0.673, 0.988; p < 0.037) lower risk of CVEs in the general population, respectively. However, our findings revealed no significant reduction in CVEs following a higher intake of soybeans.

Originality/value

In the long run, even modest consumption of legumes, but not soybeans alone, can be effective to reduce CVEs risk in a low-income population. Further studies are warranted to confirm our results in other populations, examine the associations by the type of cardiovascular events and determine any possible threshold effects in this regard.
The role of sugar products and non-alcoholic beverages in the food budget: change across birth cohorts and between socio-economic groups
Authors: Kähäri Antti
Published: May 2021

Purpose

This study investigates how the consumption of sugar products and non-alcoholic beverages has changed across birth cohorts. In addition, this study examines how the socio-economic gaps in the consumption of said products have evolved across birth cohorts.

Design/methodology/approach

The research data are drawn from the Finnish household expenditure surveys covering the period 1985–2016 (n = 44,286). An age-period-cohort methodology is utilised through the age-period-cohort-trended lag model. The model assumes that the linear long-term component of change is caused by generations replacing one-another, and that the age effect is similar across cohorts.

Findings

Sugar products and non-alcoholic beverages occupied a larger portion of more recent birth cohorts' food baskets. Cohort differences were larger in beverage consumption. Lower income was associated with a higher food expenditure share of sugar products in several cohorts. A higher education level was linked to a higher food expenditure share of sugar products in more cohorts than a lower education level. In cohorts born before the 1950s, non-alcoholic beverages occupied a larger portion of the food baskets of the high socio-economic status groups. This gap reversed over time, leading to larger food expenditure shares of non-alcoholic beverages in low socio-economic status groups.

Originality/value

This study assessed how the consumption of sugar products and non-alcoholic beverages has changed across birth cohorts. In addition, this study assessed how socio-economic differences in the consumption of said products have changed. The results highlight that sugar products and non-alcoholic beverages occupy larger portions of more recent birth cohorts’ food baskets. The results also highlight a reversal of socioeconomic differences in non-alcoholic beverage consumption.
Corruption and banking soundness: does natural resource dependency matter?
Authors: Kordbacheh Hamid , Sadati Seyedeh Zahra
Published: May 2021

Purpose

The natural resources curse theory argues the higher dependency on natural resources leads to many socio-economic problems. The purpose of this study is to examine the relationship between corruption and banking soundness and also to compare the extent of this effect between the two groups of rich and poor in natural resources countries.

Design/methodology/approach

To this aim, the authors apply a panel data set comprised of 98 countries from 2012 to 2015.

Findings

The results show that nations with a higher level of corruption have poorer banking soundness. The authors also find that by considering the resource curse theory and the effect of natural resource rents in the model, the adverse impact of corruption on banking soundness is more substantial in countries with a higher natural dependency level (rich in natural resources).

Originality/value

Though studies have been conducted on corruption and banking soundness, this paper, by using resources curse theory, articulates that corruption is one of the most critical factors affecting banking soundness and has a destructive effect on the health of the banking system and the economy of almost all countries, especially in natural resource-based economies. This study will appeal to banks authorities, governments, policymakers, oversight financial institutions and those who have a vested interest in regulating financial crimes globally. They can prevent financial and banking crises by cooperating in the fight against corruption worldwide.
Corporate governance and voluntary disclosure: evidence from India
Authors: Saha Rupjyoti , Kabra Kailash Chandra
Published: May 2021

Purpose

This study aims to examine the influence of some prominent corporate governance (CG) mechanisms such as board size (BS), board independence (BI), role duality (RD), board’s gender diversity (GD), ownership concentration (OC), audit committee independence (ACI), nomination and remuneration committee (NRC) and risk management committee (RMC) on voluntary disclosure (VD), as well as different types of VD after controlling the effect of some firm-specific factors for Indian firms.

Design/methodology/approach

The study selects market capitalization-based top 100 non-financial and non-utility firms listed on the Bombay Stock Exchange as on 31st March 2014. Data are drawn from the Capitaline Plus database over the period of 2014–2018. Appropriate panel data regression model is applied to examine the influence of CG on VD.

Findings

The study reveals a significant negative influence of BI on VD while GD and RMC exhibit a significant positive influence on the same. The remaining CG mechanisms such as BS, RD, OC, ACI and NRC appear to have no significant influence on VD. Analysis into the relationship between CG mechanisms and different types of VD reveals that BI, in particular, has a strong negative influence on corporate strategic disclosure (CSD) and forward looking disclosure (FWLD) while GD and RMC both exhibit a significant positive influence on CSD, FWLD, CG disclosure and financial and capital market disclosure. Notably, none of the CG mechanisms under consideration influence human and intellectual capital disclosure.

Research limitations/implications

The study considers annual reports as the only medium of making VD and ignores all other sources such as websites and press releases. Besides, it mainly emphasizes on corporate board structure, board committees and OC while other ownership structure-related variables family ownership, managerial ownership are not covered, which can be analysed in future studies.

Practical implications

The study offers some important theoretical, as well as practical connotations for regulators and practitioners operating in India, as well as other emerging economies having similar institutional settings.

Originality/value

The study is the first of its kind in India that examines the influence of various CG mechanisms on different types of VD and thereby contributes novel findings in the context of an emerging economy.
Digital organisational readiness: experiences from manufacturing companies
Authors: Machado Carla Gonçalves , Winroth Mats , Almström Peter , Ericson Öberg Anna , Kurdve Martin , AlMashalah Sultan
Published: May 2021

Purpose

This research aims to identify and organise the conditions of organisational readiness for digital transformation.

Design/methodology/approach

This qualitative study comprises three case studies within manufacturing companies from different sizes and industries located in Sweden. Plant visits and in-depth interviews bring to light companies' experiences with initial steps towards digital transformation. A set of conditions for digital organisational readiness was translated into a questionnaire and tested with one of the studied companies.

Findings

This paper organises and tests digital organisational readiness conditions to support companies' initial steps on digital transformation. The results are put in perspective of established change management theory and previous studies about digital transformation. The findings will conclude in a questionnaire to support dialogue and digital organisational readiness assessments.

Research limitations/implications

Additional conditions for the initial phase of digital transformation could possibly be found if more cases had been included in the study.

Practical implications

The article identifies a set of conditions translated into a questionnaire that should be used as a dialogue tool to create strategic alignment and support companies in their initial discussions. If this process can be faster and more efficient, the company can achieve a competitive advantage against competitors.

Originality/value

This research's relevance relies on the fact that companies are advancing in adopting digital technologies without being ready from an organisational perspective. This gap creates barriers for companies' digital maturing processes, stopping them from having full access to digital technologies' benefits.