bluuebunny/crossref_metadata_2025 huggingface dataset:
The incidence and in-hospital mortality of COVID-19 patients post-vaccination in eastern India
Authors: Guha Abhraneel , Chakrabarti Aritra , Bhowmick Subhrojyoti , Das Saibal , Khandelwal Rahul , Kumar Aditya , Sarkar Ajoy Krishna , Das Anupam , Ray Krishnangshu , KarPurkayastha Sujit
Published: July 2021

Objectives

The comparable effectiveness of Covishield and Covaxin vaccines has not been studied. We compared the effectiveness of Covishield and Covaxin vaccines against moderate to severe COVID-19.

Methods

In this retrospective observational study, we collected data of patients who were admitted with moderate to severe COVID-19. The vaccination status and comorbidities of the patients were documented. The incidence and in-hospital mortality of COVID-19 patients was assessed. Univariate analysis was performed to determine the risk factors of in-hospital mortality.

Results

Of 294 patients, 5.1% (n=15) received Covaxin and 26.5% (n=78) received Covishield; 68.4% (n=201) patients were unvaccinated. Of patients who were vaccinated and contracted COVID-19, 24.8% (n=73) had taken the first dose and 6.8% (n=20) had taken the second dose of either vaccine. The in-hospital mortality rate was 13.6% (n=40). 24/40 (60%) people who had hospital mortality were unvaccinated.3/40(7.5%) had succumbed to death after receiving double dose of Covishield, 11/40 (27.5%) had succumbed to death after receiving single dose of Covishield, 2/40(5%) had succumbed to death after receiving single dose of Covaxin, none had reported infection after receiving second dose of Covaxin. No significant association was found with the type of vaccine and the in-hospital mortality (p=0.23). Significant associations with in-hospital mortality were found with the interval before COVID-19 disease and vaccination (OR, 3.02; p=0.01); and the presence of diabetes mellitus (OR, 2.13; p=0.02), cardiovascular diseases (OR, 2.11; p<0.001), and malignancy (OR: 2.33; p=0.0325).

Conclusion

There was no significant difference in the effectiveness of Covaxin and Covishield in terms of the incidence of COVID-19 and in-hospital mortality. Diabetes mellitus, cardiovascular diseases, and malignancies had a significant association with in-hospital mortality in patients with moderate to severe COVID-19.
"Learn from the lessons and don't forget them": Identifying transferable lessons for COVID-19 from meningitis A, yellow fever, and Ebola virus disease vaccination campaigns
Authors: Collins Julie , Westerveld Rosie , Nelson Kate A , Rohan Hana , Bower Hilary , Lazenby Siobhan , Ikilezi Gloria , Bartlein Rebecca , Bausch Daniel G , Kennedy David S
Published: July 2021

Introduction: COVID-19 vaccines are now being distributed to low- and middle-income countries (LMICs), with global urgency surrounding national vaccination plans. LMICs have significant experience implementing vaccination campaigns to respond to epidemic threats but are often hindered by chronic health system challenges. We sought to identify transferable lessons for COVID-19 vaccination from the rollout of three vaccines that targeted adult groups in Africa and South America: MenAfriVac (meningitis A); 17D (yellow fever); and rVSV-ZEBOV (Ebola virus disease).

Methods: We conducted a rapid literature review and 24 semi-structured interviews with technical experts who had direct implementation experience with the selected vaccines in Africa and South America. We identified barriers, enablers, and key lessons from the literature and from participants' experiences. Interview data were analysed thematically according to seven implementation domains.

Results: Participants highlighted multiple components of vaccination campaigns that are instrumental for achieving high coverage. Community engagement is an essential and effective tool, requiring dedicated time, funding and workforce. Involving local health workers is a key enabler, as is collaborating with community leaders to map social groups and tailor vaccination strategies to their needs. Vaccination team recruitment and training strategies need to be enhanced to support vaccination campaigns. Although recognised as challenging, integrating vaccination campaigns with other routine health services can be highly beneficial if well planned and coordinated across health programmes and with communities.

Conclusion: As supplies of COVID-19 vaccines become available to LMICs, countries need to prepare to efficiently roll out the vaccine, encourage uptake among eligible groups, and respond to potential community concerns. Lessons from the implementation of these three vaccines that targeted adults in LMICs can be used to inform best practice for COVID-19 and other epidemic vaccination campaigns.
Analysis, quantification, and visualization of RT-LAMP technique for detection of COVID-19
Authors: Ghazimoradi Mohammad H , Daryani Maryam , Garshasbi Masoud , Zolghadr Ehsan , Khalafizadeh Ali , Babashah Sadegh
Published: July 2021

Background

SARS-Cov-2 is a new virus that caused an epidemic disease, COVID-19. According to the world health organization, detecting the patients/carriers is by the far the most important action to prevent the pandemic. Recently, the loop-mediated isothermal amplification (LAMP) technique has become more popular due to the easy handling of a one-step kit used for the detection of many diseases than RT-PCR-based techniques.

methods

Herein, we used the RT-LAMP technique so as to detect COVID-19. To this end, 40 paired-samples of patients and healthy people had been collected and tested by RT-PCR for N and E genes of SARS-CoV-2. The RT-LAMP test has been performed on samples for the RdRp gene. The sensitivity and specificity of tests have been determined.

Results

The testing results are consistent with the conventional RT-qPCR. Additionally, we also showed that a one-step process without RNA extraction is feasible to achieve RNA amplification directly from a sample.

Conclusion

We confirmed that RT-LAMP is a rapid, simple, and sensitive method that can be used as a large-screening method, particularly in regional hospitals with limited access to high-technologies.
A database of pediatric drug effects to evaluate ontogenic mechanisms from child growth and development
Authors: Giangreco Nicholas P. , Tatonetti Nicholas P.
Published: July 2021

Adverse drugs effects (ADEs) in children are common and may result in disability and death. However, current pediatric drug safety methods have not gone beyond event surveillance to identify and evaluate potential biological mechanisms. Children undergo an evolutionarily conserved and physiologically dynamic process of growth and maturation that can alter pharmacokinetics and pharmacodynamics. Our hypothesis is that temporal patterns of drug event reporting are reflective of dynamic mechanisms from child growth and development. We generated a database of 460,837 pediatric ADEs using generalized additive models (GAMs) that we have previously shown identify dynamic risk estimates of adverse drug events1. We identified 19,438 significant drug-event risks where drug risks corresponded with physiological development throughout childhood. Our results identified known pediatric drug effects and risk dynamics across child development that were not known previously. For example, we identified significant risk dynamics of montelukast-induced psychiatric disorders, including enriched risk (Odds Ratio 8.77 [2.51, 46.94]) within the second year of life. We developed a data-driven time- series clustering approach resulting in up to 95.2% precision and 97.8% sensitivity for categorizing risk dynamics across development stages for all ADEs including known but previously development-agnostic pediatric drug effects. We found that our real-world evidence may contain biologically-relevant underpinnings as well, where risk dynamics of CYP enzyme substrates were dependent on the enzyme’s expression across childhood. We curated this database for the research community to enable, for the first time, evaluation of real-world hypotheses of adverse drug effects across child growth and development.
Merfin: improved variant filtering and polishing via k-mer validation
Authors: Formenti Giulio , Rhie Arang , Walenz Brian P. , Thibaud-Nissen Françoise , Shafin Kishwar , Koren Sergey , Myers Eugene W. , Jarvis Erich D. , Phillippy Adam M.
Published: July 2021

Read mapping and variant calling approaches have been widely used for accurate genotyping and improving consensus quality assembled from noisy long reads. Variant calling accuracy relies heavily on the read quality, the precision of the read mapping algorithm and variant caller, and the criteria adopted to filter the calls. However, it is impossible to define a single set of optimal parameters, as they vary depending on the quality of the read set, the variant caller of choice, and the quality of the unpolished assembly. To overcome this issue, we have devised a new tool called Merfin (k-mer based finishing tool), a k-mer based variant filtering algorithm for improved genotyping and polishing. Merfin evaluates the accuracy of a call based on expected k-mer multiplicity in the reads, independently of the quality of the read alignment and variant caller’s internal score. Moreover, we introduce novel assembly quality and completeness metrics that account for the expected genomic copy numbers. Merfin significantly increased the precision of a variant call and reduced frameshift errors when applied to PacBio HiFi, PacBio CLR, or Nanopore long read based assemblies. We demonstrate the utility while polishing the first complete human genome, a fully phased human genome, and non-human high-quality genomes.
A nationwide genomic study of clinical Klebsiella pneumoniae in Norway 2001-2015: Introduction and spread of ESBL facilitated by CG15 and CG307
Authors: Fostervold Aasmund , Hetland Marit A.K. , Bakksjø Ragna , Bernhoff Eva , Holt Kathryn E , Samuelsen Ørjan , Simonsen Gunnar Skov , Sundsfjord Arnfinn , Wyres Kelly L , Løhr Iren H. ,   The Norwegian Study Group on Klebsiella pneumoniae
Published: July 2021

Synopsis

Objective

We have used the nationwide Norwegian surveillance program on resistant microbes in humans (NORM) to address longitudinal changes in the population structure K. pneumoniae isolates during 2001-15, encompassing the emergence and spread of ESBL-producing Enterobacterales (ESBL-E) in Norway.

Material and methods

Among blood (n= 6124) and urinary tract (n=5496) surveillance isolates from 2001-15, we used Illumina technology to whole genome sequence 201 ESBL-producing isolates from blood (n=130) and urine (n=71), and 667 non-ESBL isolates from blood. Complete genomes for four isolates were resolved with Oxford Nanopore sequencing.

Results

In a highly diverse collection, Klebsiella variicola ssp. variicola caused a quarter of Klebsiella pneumoniae species complex bacteraemias. ESBL-production was limited to K. pneumoniae sensu stricto (98.5 %). A diverse ESBL population of 57 clonal groups (CGs) were dominated by multidrug resistant CG307 (17%), CG15 (12%), CG70 (6%), CG258 (5%) and CG45 (5%) carrying blaCTX-M-15. Yersiniabactin was significantly more common in ESBL-positive (37.8%) compared to non-ESBL K. pneumoniae sensu stricto isolates (12.7%), indicating convergence of virulence and resistance determinants

Moreover, we found a significant lower prevalence of yersinabactin (3.0 %, 37.8 % and 17.3 %), IncFIB (58.7 %, 87.9 % and 79.4 %) and IncFII plasmid replicons (40.5 %, 82.8 % and 54.2%) in K. variicola ssp. variicola compared to ESBL- and non-ESBL K. pneumoniae sensu stricto, respectively.

Conclusion

The increase in Norwegian KpSC ESBLs during 2010-15 was driven by blaCTX-M-15 carrying CG307 and CG15. K. variicola ssp. variicola was a frequent cause of invasive KpSC infection, but rarely carried ESBL.
Specificity of Loxosceles α clade phospholipase D enzymes for choline-containing lipids: role of a conserved aromatic cage
Authors: Moutoussamy Emmanuel E. , Waheed Qaiser , Binford Greta J. , Khan Hanif M. , Moran Shane M. , Eitel Anna R. , Cordes Matthew H.J. , Reuter Nathalie
Published: July 2021

Spider venom GDPD-like phospholipases D (SicTox) have been identified to be one of the major toxins in recluse spider venom. They are divided into two major clades: the α clade and the β clade. Most α clade toxins present high activity against lipids with choline head groups such as sphingomyelin, while activities in β clade toxins vary and include preference for substrates containing ethanolamine headgroups (Sicarius terrosus, St_βIB1). A structural comparison of available PLDs structures reveals a conserved aromatic cage in the α clade. To test the potential influence of the aromatic cage on membrane-lipid specificity we performed molecular-dynamics (MD) simulations of the binding of several PLDs onto lipid bilayers containing choline headgroups; two SicTox from the α clade, Loxosceles intermedia αIA1 (Li_αIA) and Loxosceles laeta αIII1 (Ll_αIII1), and one from the β clade, St_βIB1. The simulation results reveal that the aromatic cage captures a choline-headgroup and suggest that the cage plays a major role in lipid specificity. We also simulated an engineered St_βIB1, where we introduced the aromatic cage, and this led to binding with choline-containing lipids. Moreover, a multiple sequence alignment revealed the conservation of the aromatic cage among the α clade PLDs. Here, we confirmed the membrane binding site of α and β clade PLDs on choline and ethanolamine-containing bilayers, respectively. Furthermore, our results suggest a major role in choline lipid recognition of the aromatic cage of the α clade PLDs. The MD simulation results are supported by in vitro liposome binding assay experiments.
The low and high postpubertal ethanol use: long-term effects on drinkers’ reproductive parameters and ethanol-naive offspring development
Authors: Fioravante Vanessa Caroline , Godoi Alana Rezende , de Barros Camargo Victória Mokarzel , Felipe Pinheiro Patricia Fernanda , Martinez Marcelo , Padovani Carlos Roberto , Martinez Francisco Eduardo
Published: July 2021

The relationship between adolescent ethanol uses and its impacts throughout life is not conclusive. Thus, we evaluated if the low and high consumption of ethanol during the postpuberty period interferes with reproduction in adulthood, the ethanol-naive offspring development and if there are dose-related effects. Females and males’ rats were divided into three groups: low drinker (L), with UChA rats fed with ethanol ad libitum drinking < 1.9 g / kg / day, high drinker (H), with UChB rats fed with ethanol ad libitum drinking from 2 to 5 g / kg / day, and control (C), with rats without access to ethanol. The L and H groups were exposed to ethanol 10% (v/ v) from 65 to 80 days, with withdrawal after this period. The study was conducted in two phases. The retrospective analysis (1st phase) verified the consumption of ethanol between sexes, the litter size, and the sex ratio of offspring. The gestational and reproductive parameters of parents and the development of pups were analyzed in the 2nd phase. We observed a higher consumption of ethanol in females and a reduced litter size in both drinkers’ groups. Body weight gain and gestational feed consumption were lower in L and H. The offspring’s body weight was also lower associated with alteration in landmarks of physical development. The high postpubertal ethanol use accents the impacts on consumers and offspring. The paternal and maternal reproductive organs weight was altered in group H, with an increase in morphologically abnormal sperm. We conclude that low and high post-pubertal alcohol consumption impairs reproductive parameters, even after withdrawal with long-term effects. Ethanol-naive offspring are also harmed, with effects associated with the dose of ethanol.
Finding Overlapping Rmaps via Gaussian Mixture Model Clustering
Authors: Mukherjee Kingshuk , Rossi Massimiliano , Dole-Muinos Daniel , Ajayi Ayomide , Prosperi Mattia , Boucher Christina
Published: July 2021

Optical mapping is a method for creating high resolution restriction maps of an entire genome. Optical mapping has been largely automated, and first produces single molecule restriction maps, called Rmaps, which are assembled to generate genome wide optical maps. Since the location and orientation of each Rmap is unknown, the first problem in the analysis of this data is finding related Rmaps, i.e., pairs of Rmaps that share the same orientation and have significant overlap in their genomic location. Although heuristics for identifying related Rmaps exist, they all require quantization of the data which leads to a loss in the precision. In this paper, we propose a Gaussian mixture modelling clustering based method, which we refer to as OMclust, that finds overlapping Rmaps without quantization. Using both simulated and real datasets, we show that OMclustsubstantially improves the precision (from 48.3% to 73.3%) over the state-of-the art methods while also reducing CPU time and memory consumption. Further, we integrated OMclustinto the error correction methods (Elmeri andcOMet) to demonstrate the increase in the performance of these methods. When OMclustwas combined withcOMetto error correct Rmap data generated from human DNA, it was able to error correct close to 3x more Rmaps, and reduced the CPU time by more than 35x. Our software is written in C++ and is publicly available under GNU General Public License athttps://github.com/kingufl/OMclust
Mutation-induced Changes in the Receptor-binding Interface of the SARS-CoV-2 Delta Variant B.1.617.2 and Implications for Immune Evasion
Authors: Baral Prabin , Bhattarai Nisha , Hossen Md Lokman , Stebliankin Vitalii , Gerstman Bernard S. , Narasimhan Giri , Chapagain Prem P.
Published: July 2021

While the vaccination efforts against SARS-CoV-2 infections are ongoing worldwide, new genetic variants of the virus are emerging and spreading. Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge the immune system as it is found that neutralizing antibodies from prior infections or vaccines are less receptive to binding with the Delta spike protein. Here, we investigated the structural changes caused by the mutations in the Delta variant’s receptor-binding interface and explored the effects on binding with the ACE2 receptor as well as with neutralizing antibodies. We find that the receptor-binding β-loop-β motif adopts an altered but stable conformation causing separation in some of the antibody binding epitopes. Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.
APOE2, E3 and E4 differentially modulate cellular homeostasis, cholesterol metabolism and inflammatory response in isogenic iPSC-derived astrocytes
Authors: de Leeuw Sherida M. , Kirschner Aron W. T. , Lindner Karina , Rust Ruslan , Wolski Witold E. , Gavin Anne-Claude , Nitsch Roger M. , Tackenberg Christian
Published: July 2021

Apolipoprotein E (APOE) is the principal lipid carrier in the CNS and mainly expressed by astrocytes. The three different APOE alleles (E2, E3, and E4) impose differential risk to Alzheimer’s disease (AD); E2 is protective, E3 is defined as average risk, while E4 is the major genetic risk factor for sporadic AD. Despite recent advances, the fundamental role of different APOE alleles in brain homeostasis is still poorly understood. To uncover the functional role of APOE in human astrocytes, we differentiated human APOE-isogenic iPSCs (E4, E3, E2 and APOE-knockout (KO)) to functional astrocytes (hereafter “iAstrocytes”), with a resting, non-proliferating phenotype. Functional assays indicated that polymorphisms in APOE (APOE4>E3>E2=KO) reduced iAstrocyte metabolic and clearance functions including glutamate uptake and receptor-mediated uptake of β-amyloid aggregates. We performed unlabelled mass spectrometry-based proteomic analysis of iAstrocytes at baseline and after activation with interleukin-1β (IL-1β) showing a reduction of cholesterol and lipid metabolic and biosynthetic pathways, and an increase of immunoregulatory pathways at baseline (E4>E3>E2). Cholesterol efflux and biosynthesis were reduced in E4 iAstrocytes, and subcellular localization of cholesterol in lysosomes was increased. In APOE-KO iAstrocytes, APOE-independent mechanisms showed to be proficient in mediating cholesterol biosynthesis and efflux. Proteomic analysis of IL-1β-treated iAstrocytes showed an increase of cholesterol/lipid metabolism and biosynthesis as well as inflammatory pathways. Furthermore, cholesterol efflux, which was reduced in APOE4 iAstrocytes at baseline, was alleviated in activated E4 iAstrocytes. Inflammatory cytokine release was exacerbated upon IL-1β treatment in E4 iAstrocytes (E4>E3>E2>KO), in line with the proteomic data. Taken together, we show that APOE plays a major role in several physiological and metabolic processes in human astrocytes with APOE4 pushing iAstrocytes to a disease-relevant phenotype, causing dysregulated cholesterol/lipid homeostasis, increased inflammatory signalling and reduced β-amyloid uptake while APOE2 iAstrocytes show opposing effects.

Our study provides a new reference for AD-relevant proteomic and metabolic changes, mediated by the three main APOE isoforms in human astrocytes.
Genome-Wide Detection of Imprinted Differentially Methylated Regions Using Nanopore Sequencing
Authors: Akbari Vahid , Garant Jean-Michel , O’Neill Kieran , Pandoh Pawan , Moore Richard , Marra Marco A. , Hirst Martin , Jones Steven J.M.
Published: July 2021

Imprinting is a critical part of normal embryonic development in mammals, controlled by defined parent-of-origin (PofO) differentially methylated regions (DMRs) known as imprinting control regions. As we and others have shown, direct nanopore sequencing of DNA provides a mean to detect allelic methylation and to overcome the drawbacks of methylation array and short-read technologies. Here we leverage publicly-available nanopore sequence data for 12 standard B-lymphocyte cell lines to present the first genome-wide mapping of imprinted intervals in humans using this technology. We were able to phase 95% of the human methylome and detect 94% of the well-characterized imprinted DMRs. In addition, we found 28 novel imprinted DMRs (12 germline and 16 somatic), which we confirmed using whole-genome bisulfite sequencing (WGBS) data. Analysis of WGBS data in mus musculus, rhesus macaque, and chimpanzee suggested that 12 of these are conserved. We also detected subtle parental methylation bias spanning several kilobases at seven known imprinted clusters. These results expand the current state of knowledge of imprinting, with potential applications in the clinic. We have also demonstrated that nanopore long reads, can reveal imprinting using only parent-offspring trios, as opposed to the large multi - generational pedigrees that have previously been required.
Machine-learning-based predictions of caloric restriction associations across ageing-related genes
Authors: Vega-Magdaleno Gustavo Daniel , Bespalov Vladislav , Zheng Yalin , Freitas Alex A. , de Magalhaes Joao Pedro
Published: July 2021

Caloric restriction (CR) is the most studied pro-longevity intervention; however, a complete understanding of its underlying mechanisms remains elusive, and new research directions may emerge from the identification of novel CR-related genes and CR-related genetic features. This work used a Machine Learning (ML) approach to classify ageing-related genes as CR-related or NotCR-related using 9 different types of predictive features: PathDIP pathways, two types of features based on KEGG pathways, two types of Protein-Protein Interactions (PPI) features, Gene Ontology (GO) terms, Genotype-Tissue Expression (GTEx) expression features, Gene-Friends co-expression features and protein sequence descriptors. Our findings suggested that features biased towards curated knowledge (i.e. GO terms and biological pathways), had the greatest predictive power, while unbiased features (mainly gene expression and co-expression data) have the least predictive power. Moreover, a combination of all the feature types diminished the predictive power compared to predictions based on curated knowledge. Feature importance analysis on the two most predictive classifiers mostly corroborated existing knowledge and supported recent findings linking CR to the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) signalling pathway and G protein-coupled receptors (GPCR). We then used the two strongest combinations of feature type and ML algorithm to predict CR-relatedness among ageing-related genes currently lacking CR-related annotations in the data, resulting in a set of promising candidate CR-related genes (GOT2, GOT1, TSC1, CTH, GCLM, IRS2 and SESN2) whose predicted CR-relatedness remain to be validated in future wet-lab experiments.
Probing the toxic interactions between the reactive dye Drimaren Red and Human Serum Albumin
Authors: Menezes Thaís Meira , de Assis Caio Rodrigo Dias , da Silva Neto Antônio Marinho , Gubert Priscila , Ghislandi Marcos Gomes , Neves Jorge Luiz
Published: July 2021

Azo dyes like Drimaren Red CL-5B (DR, CI Reactive Red 241) represent a class of compounds extensively used in the textile industry and are extremely dangerous to the environment and human health. Therefore, understanding the binding characteristics between such substances and biological macromolecules is essential from a toxic-kinetic perspective. The molecular interaction between DR and Human Serum Albumin (HSA) was investigated through spectroscopic techniques and molecular docking approaches. The results indicate that DR quenches HSA fluorescence following a static mechanism (corroborated by UV-Vis studies) with a moderate interaction (Ka~105 M−1), guided by electrostatic interactions (ΔS°> 0 and ΔH°< 0). DR is 5.52 nm distant from fluorophore residue Trp-214 (according to FRET investigations), and the interaction is mainly related to Tyr residues (as revealed by synchronous fluorescence). The Ellman assay identified a decrease in the content of HSA free thiol. The results of the RLS demonstrate that there are HSA alterations, suggesting damage to the confirmation of the protein. Molecular docking suggests the binding site of DR was located in subdomain IIB HSA, corroborating the experimental properties. Finally, the results suggest a high potential for DR toxicity triggered by contact with key proteins, which affects the biomolecule functionalities.
Amplification-free detection of viral RNA by super resolution imaging-based CRISPR/Cas13a System
Authors: He Qian , Chen Qun , Li Fang , Yuan Xi , Wang Chuhui , Liu Changyue , Xu Lidan , Zhong Xiaoyun , Wei Jiazhang , Pandey Vijay , Yu Dongmei , Dong Yuhan , Zhang Yongbing , Deng Lin , Du Ke , Qin Peiwu
Published: July 2021

RNA detection is crucial for biological research and clinical diagnosis. The current methods include both direct and amplification-based RNA detection. These methods require complicated procedures, suffering from low sensitivity, slow turnaround, and amplification bias. The CRISPR/Cas13a system is a direct RNA detection method via target RNA induced collateral cleavage activity. However, to detect low concentration RNA with CRISPR/Cas13a, target amplification is always required. Herein, we optimize the components of the CRISPR/Cas13a assay to enhance the sensitivity of viral RNA detection which improve the detection limit from 1 pM up to 100 fM. In addition, the integration of CRISPR/Cas13a biosensing and single molecule super resolution imaging is a novel strategy for direct and amplification-free RNA detection. After surface modification, fluorescent RNA reporters are immobilized on the glass coverslip surface and fluorescent signals are captured by total internal reflection fluorescence microscopy (TIRFM), shifting the measurement from spectroscopy to imaging. We quantify the fluorescence signal intensity before and after collateral cleavage of the CRISPR system when viral RNA is present and achieve a detection limit of 10 fM. Therefore, we provide a novel TIRFM-based system to visualize the CRISPR trans-cleavage for direct and robust RNA detection.
Open access in silico tools to predict the ADMET profiling and PASS (Prediction of Activity Spectra for Substances of Bioactive compounds of Garlic (Allium sativum L.)
Authors: Ferrari Ivan Vito
Published: July 2021

Background

Garlic (Allium sativum L.) is a common spice with many health benefits, mainly due to its diverse bioactive compounds, (see below) such as organic sulphides, saponins, phenolic compounds, and polysaccharides. Several studies have demonstrated its functions such as anti-inflammatory, antibacterial, and antiviral, antioxidant, cardiovascular protective and anticancer property. In this work we have investigated the main bioactive components of garlic through a bioinformatics approach. Indeed, we are in an era of bioinformatics where we can predict data in the fields of medicine. Approaches with open access in silico tools have revolutionized disease management due to early prediction of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of the chemically designed and eco-friendly next-generation drugs.

Methods

This paper encompasses the fundamental functions of open access in silico prediction tools, as PASS database (Prediction of Activity Spectra for Substances) that it estimates the probable biological activity profiles for compounds. This paper also aims to help support new researchers in the field of drug design and to investigate best bioactive compounds in garlic.

Results

screening through each of pharmacokinetic criteria resulted in identification of Garlic compounds that adhere to all the ADMET properties.

Conclusions

It was established an open-access database (PASS database, available bioinformatics tool SwissADME, PreADMET pkCSM database) servers were employed to determine the ADMET (metabolism, distribution, excretion, absorption, and toxicity) attributes of garlic molecules and to enable identification of promising molecules that follow ADMET properties.

Graphical abstract
Deep neural language modeling enables functional protein generation across families
Authors: Madani Ali , Krause Ben , Greene Eric R. , Subramanian Subu , Mohr Benjamin P. , Holton James M. , Olmos Jose Luis , Xiong Caiming , Sun Zachary Z. , Socher Richard , Fraser James S. , Naik Nikhil
Published: July 2021

Bypassing nature’s evolutionary trajectory,de novoprotein generation—defined as creating artificial protein sequences from scratch—could enable breakthrough solutions for biomedical and environmental challenges. Viewing amino acid sequences as a language, we demonstrate that a deep learning-based language model can generate functional artificial protein sequences across families, akin to generating grammatically and semantically correct natural language sentences on diverse topics. Our protein language model is trained by simply learning to predict the next amino acid for over 280 million protein sequences from thousands of protein families, without biophysical or coevolutionary modeling. We experimentally evaluate model-generated artificial proteins on five distinct antibacterial lysozyme families. Artificial proteins show similar activities and catalytic efficiencies as representative natural lysozymes, including hen egg white lysozyme, while reaching as low as 44% identity to any known naturally-evolved protein. The X-ray crystal structure of an enzymatically active artificial protein recapitulates the conserved fold and positioning of active site residues found in natural proteins. We demonstrate our language model’s ability to be adapted to different protein families by accurately predicting the functionality of artificial chorismate mutase and malate dehydrogenase proteins. These results indicate that neural language models successfully performde novoprotein generation across protein families and may prove to be a tool to shortcut evolution.
TAF4b transcription networks regulating early oocyte differentiation
Authors: Gura Megan A. , Relovska Sona , Abt Kimberly M. , Seymour Kimberly A. , Wu Tong , Kaya Haskan , Turner James M. A. , Fazzio Thomas G. , Freiman Richard N.
Published: July 2021

Establishment of a healthy ovarian reserve is contingent upon numerous regulatory pathways during embryogenesis. Previously, mice lacking TBP-associated factor 4b (Taf4b) were shown to exhibit a diminished ovarian reserve. However, potential oocyte-intrinsic functions of TAF4b have not been examined. Here we use a combination of gene expression profiling and chromatin mapping to characterize the TAF4b gene regulatory network in mouse oocytes. We find thatTaf4b-deficient oocytes display inappropriate expression of meiotic, chromatin, and X-linked genes, and unexpectedly we found a connection with Turner Syndrome pathways. Using Cleavage Under Targets and Release Using Nuclease (CUT&RUN), we observed TAF4b enrichment at genes involved in meiosis and DNA repair, some of which are differentially expressed inTaf4b-deficient oocytes. Interestingly, TAF4b target genes were enriched for Sp/KLF family motifs rather than TATA-box, suggesting an alternate mode of promoter interaction. Together, our data connects several gene regulatory nodes that contribute to the ovarian reserve.
Natural immunity against COVID-19 significantly reduces the risk of reinfection: findings from a cohort of sero-survey participants
Authors: Mishra Bijaya Kumar , Bhattacharya Debdutta , Kshatri Jaya Singh , Pati Sanghamitra
Published: July 2021

Conflicting reports on the persistence of antibody levels in individuals recovered from COVID-19 infection, suggest that the immunity against COVID-19 may not be lasting for long. In India, by 30th June, 2021, not less than 30 million people were infected with COVID-19 and 0.39 million people were reported to have lost their life to the disease in India. I the current study we followed up with a subsample of our previous sero-survey participants to assess whether natural immunity against SARS-CoV-2 was associated with a reduced risk of re-infection. We conducted telephonic interview of a total of 3038 participants, out of which 2238 participants responded and 5 participants were found to be not alive, as conveyed by their close relatives. There was a non-response rate of 26.1%. Out of the 2238 participants, 1170 were sero-positive and 1068 were sero-negative for antibody against COVID-19. Our survey found that only 3 individuals in the sero-positive group got infected with COVID-19 whereas 127 individuals reported contracting the infection the sero-negative group. Interestingly, from the 127 sero-negative individuals who later contracted COVID-19 infection, 30 needed hospitalization, out of which 12 were on oxygen therapy, four in ICU and one was on ventilator. At the other hand, from the 3 sero-positives re-infected with COVID-19, one had hospitalization, but didnnot require oxygen support or critical care. These findings reinforce the strong plausibility that development of antibody following natural infection not only protects against re-infection by the virus to a great extent, but also safeguards against progression to severe COVID-19 disease.
Developing orbital-free quantum crystallography: the local potentials and associated partial charge densities
Authors: Tsirelson Vladimir , Stash Adam
Published: July 2021

This work extends the orbital-free density functional theory to the field of quantum crystallography. The total electronic energy is decomposed into electrostatic, exchange, Weizsacker and Pauli components on the basis of physically grounded arguments. Then, the one-electron Euler equation is re-written through corresponding potentials, which have clear physical and chemical meaning. Partial electron densities related with these potentials by the Poisson equation are also defined. All these functions were analyzed from viewpoint of their physical content and limits of applicability. Then, they were expressed in terms of experimental electron density and its derivatives using the orbital-free density functional theory approximations, and applied to the study of chemical bonding in a heteromolecular crystal of ammonium hydrooxalate oxalic acid dihydrate. It is demonstrated that this approach allows the electron density to be decomposed into physically meaningful components associated with electrostatics, exchange, and spin-independent wave properties of electrons or with their combinations in a crystal. Therefore, the bonding information about a crystal that was previously unavailable for X-ray diffraction analysis can be now obtained.
New Zealand study of not-for-profit (NFP) shows high degree of employee involvement doesn't produce results without strong HRM policies
Authors: Smith David
Published: July 2021

Purpose

There is a growing interest in employee involvement as a means to enhance commitment and wellbeing. Typically, there is a degree of power sharing in decisions at all levels. In large organizations, the strategy has been shown to deliver benefits. The authors wanted to study the themes in a small NFP.

Design/methodology/approach

The authors chose an extreme case of a small NFP organized on democratic lines but with only informal HRM policies. They felt an extreme case would be instructive. The organization, which they gave the pseudonym OA, is a small non-profit agency that offers education around sexual violence and advice and support to survivors. As a collective, it involves everyone in decision-making. The lead author carried out the detailed study over six months based in the office. It involved formal interviews with six existing employees and six ex-employees, or volunteers, as well as a clinical supervisor.

Findings

The study showed that without systematic and strategic HRM policies, strong forms of employee participation won’t deliver higher levels of equity. Although the NFP in the study operated as a collective, it lacked even basic HR policies. The consequences included poor management, high turnover, burnout and inadequate training.

Originality/value

The authors said the results showed that small size and organizational commitment did not always support effective employee participation. Weak HR policies made the problems of poor communication and decision-making worse and caused a lot of stress. As a result, the high turnover impacted performance. The findings add a note of caution to existing findings about employee participation. In fact, perversely, it can even lead to worse outcomes. Arguably, they say, HRM is even more essential in a small NFP environment because of the structural constraints and lack of funding.
Analytical hierarchy processes and Pareto analysis for mitigating cybercrime in the financial sector
Authors: Akinbowale Oluwatoyin Esther , Klingelhöfer Heinz Eckart , Zerihun Mulatu Fekadu
Published: July 2021

Purpose

The purpose of this study is to use a decision support model based on the Analytical Hierarchy Process (AHP) and Pareto analysis (PA) for ranking the impact of different kinds of cybercrime in organisations in the financial sector to support decisions on cybercrime mitigation.

Design/methodology/approach

From a structured questionnaire to the staff of 17 licensed banks in South Africa in charge of management, administration and operations, the perceived effect of cybercrime on the organisation’s goals, namely, organisation’s profitability, goodwill, customers’ satisfaction and risk management was derived. The pairwise comparison of the organisation’s goals and identified forms of cybercrime was done using the AHP.

Findings

The results obtained indicate that there was a consensus (100% of the answers) that the effect of cybercrime has negatively impacted the organisation’s objectives profitability and goodwill. Also, still 95.23% of the respondents agreed that the effect of cybercrime has negatively impacted the level of customers’ satisfaction, while only 7.15% saw an impact on the organisation’s risk management processes. Using these results in the AHP, analysis delivers a hierarchical order about the relevance of prevalent forms of cybercrime for the organisation´s cybercrime mitigation. The PA further shows the magnitude of the forms of cybercrime relative to each other.

Practical implications

Hence, this study provides a decision support framework for organisational management in the quest to explore the impact of cyber fraud. It can serve as a practical guided approach for the application of AHP analysis for the existing and emerging forms of cybercrime.

Originality/value

The novelty of this study lies in the fact that the combination of the AHP and PA to support solving a multi-criteria decision problem relating to the prevalence of cybercrime has not been sufficiently highlighted by the existing literature.
Completeness of the qualitative characteristics using Foucauldian critical discourse analysis and content analysis paradigms: towards a revised conceptual framework
Authors: Evans Gareth , Lusher Joanne , Day Stephen
Published: July 2021

Purpose

The qualitative characteristics of decision-useful financial information (as set out in the revised March 2018 Conceptual Framework for financial reporting of the International Accounting Standards Board [IASB]) are fundamental for standard setting relied on by companies when making accounting policy changes and choices. However, there has not been an overarching universally agreed conceptual context of the qualitative characteristics. This paper aims to study the completeness of the qualitative characteristics towards suggesting a revision of the Conceptual Framework.

Design/methodology/approach

The present study evaluated the completeness of these qualitative characteristics using Foucauldian critical discourse analysis and content analysis paradigms to elucidate the inclusion conundrum. Foucauldian analysis allowed focus on power relationships, governmentality and subjectification in accounting society, as expressed through language and practices of the IASB who ultimately decide on the qualitative characteristics. Content analysis was used to analyse data collected via interviews with preparers and users of banks’ accounts, changes in banks’ accounting policies after the conceptual framework was published and comment letters from banks who wrote to the IASB.

Findings

Novel findings from this study revealed the potential significant omissions of the constraints of “materiality”, “transparency” and “regulatory/supervisory framework”. Also, surrounding the qualitative characteristics having been shown to be valid and includable, the adjective “decision-useful” reinstated in the chapter title and the IASB project team technical writers needing to show completeness of attention to all comments.

Originality/value

From these findings, a freshly formulated chapter in the conceptual framework on the qualitative characteristics can now be submitted for consideration by the IASB, with potential for international post-implementation review.
Pracademia: an answer but not the answer to an enduring question
Authors: Eacott Scott
Published: July 2021

Purpose

The pracademia movement is gaining increasing traction in education, particularly in educational leadership. Offered as a means to bridge practice and academia, questions remain as to whether it resolves or perpetuates the theory–practice divide. This paper systematically approaches this problem.

Design/methodology/approach

Theoretically informed by the relational approach, this conceptual paper articulates the preliminaries and underlying assumptions of pracademia before exploring the implications for the field of educational leadership.

Findings

Having established the underlying assumptions, this paper offers three standards – description, explanation and alternative – for assessing knowledge claims in the field that does not default to distinct knowledge worlds (e.g. academic, practice) or categories of knowledge generators (e.g. academics, practitioners, pracademics).

Originality/value

Through a relational approach, this work breaks down the boundaries of theory and practice to offer a new way of thinking about knowledge claims. The new approach is consistent with the intent of bridging theory and practice without the need to assume them to be separate in the first place.
A conceptual framework for an agile asset performance management process
Authors: Karar Ahmed Noaman , Labib Ashraf , Jones Dylan Francis
Published: July 2021

Purpose

Disturbances in terms of major crises such as pandemics, fluctuations in demand and oil price, energy consumption and supply chain can significantly impair the maintenance programs effectiveness and efficiency. Hence, there is an urgent need for an agile asset performance management (AAPM) framework.

Design/methodology/approach

This paper's main objective is to design a comprehensive framework for an AAPM system that sustains the desired asset performance by reacting efficiently, quickly and intelligently to the changes in the operating context parameters and asset health conditions. Such a framework is adaptive to changes in scenarios and aims to systematise the decision support process, considering different objectives.

Findings

The development of the proposed framework has led to identifying an innovative way of seamless integration between crucial reliability and asset management tools. Also, the methodology implementation is expected to promote the practical use of its reliability tools and enable asset stakeholders to break silo working for clear communication around asset performance.

Originality/value

The implementation of the AAPM framework follows a new approach developed during this research and coined by the authors as the “8S approach.”
Effects of V/III ratio of InGaN quantum well at high growth temperature for near ultraviolet light emitting diodes
Authors: Md Sahar Mohd Ann Amirul Zulffiqal , Hassan Zainuriah , Ng Sha Shiong , Lim Way Foong , Lau Khai Shenn , Alias Ezzah Azimah , Ahmad Mohd Anas , Hamzah Nur Atiqah , Mohd Asri Rahil Izzati
Published: July 2021

Purpose

The aims of this paper is to study the effects of the V/III ratio of indium gallium nitride (InGaN) quantum wells (QWs) on the structural, optical and electrical properties of near-ultraviolet light-emitting diode (NUV-LED).

Design/methodology/approach

InGaN-based NUV-LED is successfully grown on the c-plane patterned sapphire substrate at atmospheric pressure using metal organic chemical vapor deposition.

Findings

The indium composition and thickness of InGaN QWs increased as the V/III ratio increased from 20871 to 11824, according to high-resolution X-ray diffraction. The V/III ratio was also found to have an important effect on the surface morphology of the InGaN QWs and thus the surface morphology of the subsequent layers. Apart from that, the electroluminescence measurement revealed that the V/III ratio had a major impact on the light output power (LOP) and the emission peak wavelength of the NUV-LED. The LOP increased by up to 53% at 100 mA, and the emission peak wavelength of the NUV-LED changed to a longer wavelength as the V/III ratio decreased from 20871 to 11824.

Originality/value

This study discovered a relation between the V/III ratio and the properties of QWs, which resulted in the LOP enhancement of the NUV-LED. High TMIn flow rates, which produced a low V/III ratio, contribute to the increased LOP of NUV-LED.