bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review on the theory of stable dendritic growth
Authors: Alexandrov Dmitri V. , Galenko Peter K. 
Published: July 2021

This review article summarizes the main outcomes following from recently developed theories of stable dendritic growth in undercooled one-component and binary melts. The nonlinear heat and mass transfer mechanisms that control the crystal growth process are connected with hydrodynamic flows (forced and natural convection), as well as with the non-local diffusion transport of dissolved impurities in the undercooled liquid phase. The main conclusions following from stability analysis, solvability and selection theories are presented. The sharp interface model and stability criteria for various crystallization conditions and crystalline symmetries met in actual practice are formulated and discussed. The review is also focused on the determination of the main process parameters—the tip velocity and diameter of dendritic crystals as functions of the melt undercooling, which define the structural states and transitions in materials science (e.g. monocrystalline-polycrystalline structures). Selection criteria of stable dendritic growth mode for conductive and convective heat and mass fluxes at the crystal surface are stitched together into a single criterion valid for an arbitrary undercooling.This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
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

AbstractObjectivesThe 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.MethodsIn 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.ResultsOf 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).ConclusionThere 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.
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

AbstractBackgroundSARS-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.methodsHerein, 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.ResultsThe 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.ConclusionWe 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.
Development and validation of a clinical risk score to predict SARS-CoV-2 infection in emergency department patients: The CCEDRRN COVID-19 Infection Score (CCIS)
Authors: McRae Andrew D , Hohl Corinne M , Rosychuk Rhonda J , Vatanpour Shabnam , Ghaderi Gelareh , Archambault Patrick M , Brooks Steven C , Cheng Ivy , Davis Philip , Hayward Jake , Lang Eddy S , Ohle Robert , Rowe Brian H. , Welsford Michelle , Yadav Krishan , Morrison Laurie J , Perry Jeffrey J. ,   Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) investigators for the Network of Canadian Emergency Researchers and the Canadian Critical Care Trials Group
Published: July 2021

AbstractObjectivesTo develop and validate a clinical risk score that can accurately quantify an emergency department patient’s probability of SARS-CoV-2 infection without the need for laboratory testingDesignCohort study of participants in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) registry. Regression models were fitted to predict a positive SARS-CoV-2 test result using clinical and demographic predictors, as well as an indicator of local SARS-CoV-2 incidence.Setting32 emergency departments in eight Canadian provincesParticipants27,665 consecutively-enrolled patients who were tested for SARS-CoV-2 in participating emergency departments between March 1-October 30,2020Main outcome measuresPositive SARS-CoV-2 nucleic acid test result within 14 days of an index emergency department encounter for suspected COVID-19 diseaseResultsWe derived a 10-item CCEDRRN COVID-19 Infection Score using data from 21,743 patients. This score included variables from history and physical examination, and an indicator of local disease incidence. The score had a c-statistic of 0.838 with excellent calibration. We externally validated the rule in 5,295 patients. The score maintained excellent discrimination and calibration, and had superior performance compared to another previously published risk score. Score cutoffs were identified that can rule-in or rule-out SARS-CoV-2 infection without the need for nucleic acid testing with 97.4 % sensitivity (95% CI 96.4–98..3) and 95.9% specificity (95% CI 95.5-96.0).ConclusionsThe CCEDRRN COVID-19 Infection Score uses clinical characteristics and publicly available indicators of disease incidence to quantify a patient’s probability of SARS-CoV-2 infection. The score can identify patients at sufficiently high risk of SARS-CoV-2 infection to warrant isolation and empiric therapy prior to test confirmation, while also identifying patients at sufficiently low risk of infection that they may not need testing.Trial registrationCCEDRRN is registered at clinicaltrials.gov (NCT04702945).FundingThe network is funded by the Canadian Institutes of Health Research (447679), BC Academic Health Science Network Society, BioTalent Canada, Genome BC (COV024; VAC007), Ontario Ministry of Colleges and Universities (C-655-2129), the Saskatchewan Health Research Foundation (5357) and the Fondation CHU de Québec (Octroi #4007). These organizations are not-for-profit, and had no role in study conduct, analysis, or manuscript preparation.
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

AbstractAdverse 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

AbstractRead 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

SynopsisObjectiveWe 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 methodsAmong 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.ResultsIn 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 determinantsMoreover, 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.ConclusionThe 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

ABSTRACTSpider 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

AbstractThe 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

ABSTRACTOptical 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

AbstractWhile 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

AbstractApolipoprotein 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.