bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid genotyping of tilapia lake virus (TiLV) using Nanopore sequencing
Authors: Delamare-Deboutteville Jerome , Taengphu Suwimon , Gan Han Ming , Kayansamruaj Pattanapon , Debnath Partho Pratim , Barnes Andrew , Wilkinson Shaun , Kawasaki Minami , Mohan Chadag Vishnumurthy , Senapin Saengchan , Dong Ha Thanh 
Published: March 2021

AbstractInfectious diseases represent one of the major challenges to sustainable aquaculture production. Rapid, accurate diagnosis and genotyping of emerging pathogens during early-suspected disease cases is critical to facilitate timely response to deploy adequate control measures and prevent or reduce spread. Currently, most laboratories use PCR to amplify partial pathogen genomic regions, occasionally combined with sequencing of PCR amplicon(s) using conventional Sanger sequencing services for confirmatory diagnosis. The main limitation of this approach is the lengthy turnaround time. Here, we report an innovative approach using a previously developed specific PCR assay for pathogen diagnosis combined with a new Oxford Nanopore Technologies (ONT)-based amplicon sequencing method for pathogen genotyping. Using fish clinical samples, we applied this approach for the rapid confirmation of PCR amplicon sequences identity and genotyping of tilapia lake virus (TiLV), a disease-causing virus affecting tilapia aquaculture globally. The consensus sequences obtained after polishing exhibit strikingly high identity to references derived by Illumina and Sanger methods (99.83-100%). This study suggests that ONT-based amplicon sequencing is a promising platform to deploy in regional aquatic animal health diagnostic laboratories in low and medium income countries, for fast identification and genotyping of emerging infectious pathogens from field samples within a single day.
Mitigating the identity and health threat of COVID-19: Perspectives of Middle-Class South Asians living in the UK
Authors: Hanson Kristin , O’Dwyer Emma , Chauduri Sharmistha , Silva Souza Luiz Gustavo , Vandrevala Tushna 
Published: March 2021

AbstractThe recognition and representation of BAME community as “high risk” of Covid-19 in the UK presents both a health and an identity threat to this ethnic group. This study employed thematic analysis to explore response to these threats as related by a sample of thirteen middle class members of the South Asian community. This work advances both health and identity psychological theory by recognising the affinity between expressions of health efficacy and identity. Our findings identify South Asian intragroup stigmatisation and commonalities that have implications for the promotion of health behaviour and health communications for minority groups.
An individual participant data meta-analysis of prognostic blood biomarkers in IPF
Authors: Khan Fasihul A , Stewart Iain , Saini Gauri , Robinson Karen A. , Jenkins R Gisli 
Published: March 2021

ABSTRACTBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with variable disease trajectory. Blood biomarkers reflecting disease severity that can accurately predict outcomes are urgently needed. Through systematic review and meta-analysis, we evaluate the prognostic potential of matrix-metalloproteinase-7 (MMP-7) and other frequently studied blood biomarkers in patients with IPF.MethodsElectronic databases were searched on 12th November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline or change over three months. Individual participant data (IPD) was sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality, with secondary outcomes including disease progression, defined as >10% relative FVC decline or death.Results29 studies reporting outcomes from 3950 IPF participants were included, investigating a total of 16 biomarkers. IPD from MMP-7 studies was available for eleven cohorts. Baseline MMP-7 levels were associated with increased mortality (adjusted HR1.23 per SD increase, 95%CI 1.03;1.48, I2=64.3%) and disease progression (adjusted OR1.27 per SD increase, 95%CI 1.11;1.46, I2=5.9%), but change in MMP-7 over three-months was not associated with any of the measured outcomes. There was insufficient data for quantitative analysis in non-MMP7 studies, and whilst many biomarkers showed an association with clinical outcomes, replication of effects across studies was weak.ConclusionBaseline MMP-7 levels were associated with an increased risk of overall mortality and disease progression in patients with untreated IPF. The evidence for other biomarkers is currently insufficient with further studies needed.
A time series forecasting of the proportion of SARS-CoV-2 N501Y lineage in North America
Authors: Quinonez Elena , Vahed Majid , Shahraki Abdolrazagh Hashemi , Mirsaeidi Mehdi 
Published: March 2021

AbstractIntroductionThe outbreak of pneumonia known as SARS-COV-2 and newly-emerging South African (B.1.351), the United Kingdom (B.1.1.7) and Brazil (P.1) variants have led to a more infectious virus and potentially more substantial loss of neutralizing activity by natural infection or vaccine-elicited antibodies.MethodsWe identified prevalent mutations using the spike receptor-binding domain (S-RBD) of SARS-CoV-2 deposited in the Nextstrain global database and comparing them to the Wuhan-Hu-1/2019 genomic sequence as a reference. Then we calculated the percentages of mutant genomes from the total regional subsample isolates from December 2019 to the end of January 2021. We developed two separate time series forecasting models for the SARS-CoV-2 B.1.1.7 variant. The computational model used the structure of the S-RBD to examine its interactions with the neutralizing antibody, named CV30 (isolated from a patient), and human angiotensin-converting enzyme 2 (hACE-2), based on a hybrid algorithm of template-based modeling to predict the affinity of S protein to the neutralizing antibodies and hACE-2 receptor.ResultsThe proportion of the B.1.1.7 strain in North America is growing fast. From these computations, it seems that the S-RBD and hACE-2 proteins are less favorable for the South African strain (K417N, E484K, and N501Y) as compared to the wild type structure and more favorable for B.1.1.7 and P.1 variants. In the present of crystallized CV30 neutralizing antibodies, docking scores suggest antibodies can be partially neutralize the B.1.1.7 variant, and, less efficiently, the B.1.351 and P.1 variants.ConclusionThe rapid evolution of SARS-CoV-2 has the potential to allow the newly-emerged B.1.351, and P.1 variants to escape from natural or vaccine-induced neutralizing immunity and viral spreading.
Has the age distribution of hospitalized Covid-19 patients changed in Brazil?
Authors: de Andrade Carla Lourenço Tavares , Lima Sheyla Maria Lemos , Martins Monica , Pereira Claudia Cristina de Aguiar , Portela Margareth Crisóstomo 
Published: March 2021

AbstractThe aim of this study was to compare the age profile of hospitalized Covid-19 patients during the first year of the pandemic, as well as hospital mortality and use of ICUs, by age group, in large geographic regions of Brazil. We used data from the Influenza Epidemiological Surveillance Information System for patients who presented the first symptoms of the disease between the epidemiological weeks 8 of 2020 and 7 of 2021, which were divided into three periods.779,257 records of patients hospitalized by Covid-19 were obtained. Of this total, 720,363 (92.4%) referred to discharged hospitalizations, considered in the analysis of ICU use and death. Among 244,611 hospitalizations (34.0%) with indication for use of ICU, 190,833 allowed the calculation of the time in ICU. There was variation in the age profile of hospitalized patients between the three periods, but there was no evidence in favor of the hypothesis of an increase, in the last period, in the participation of adults between 18 and 50 years old in hospitalizations by Covid-19. A differentiated increase in the mortality of young adults in the North suggests the possibility of greater severity of the P1 variant in this population. The results also show that the participation of young adults in hospitalizations and hospital deaths was never negligible and is related to hospital mortality rates close to or above 10%.The Covid-19 “youthening” phenomenon in Brazil is based on the country’s own sociodemographic and economic characteristics and may have been strengthened by the increasing circulation of viral variants. It is important to continue monitoring its progression and effects.
Why did the children stop coming? Reasons for paediatric emergency department attendance decrease during the first wave of the COVID-19 pandemic in the United Kingdom: A qualitative study
Authors: Breckons Matthew , Thorne Sophie , Walsh Rebecca , Bhopal Sunil , Owens Stephen , Rankin Judith 
Published: March 2021

AbstractUK ‘Lockdown’ measures introduced in March 2020 aimed to mitigate the spread of Covid-19. Although seeking healthcare was still permitted within restrictions, paediatric emergency department attendances reduced dramatically and led to concern over risks caused by delayed presentation. Our aim was to gain insight into healthcare decisions faced by parents during the first wave of the Covid-19 pandemic and to understand if use of urgent healthcare, self-care, and information needs differed during lockdown as well as how parents perceived risks of Covid-19.We undertook qualitative telephone interviews with a purposive sample of parents living in the North East of England recruited through online advertising. We used a semi-structured topic guide to explore past and current healthcare use, perceptions of risk and the impact of the pandemic on healthcare decisions. Interviews were transcribed and analysed using Thematic Analysis.Three major themes were identified which concerned (i) how parents made sense of risks posed to, and by their children, (ii) understanding information regarding health services and (iii) attempting to make the right decision. These themes contribute to the understanding of the initial impact of Covid-19 and associated restrictions on parental decisions about urgent healthcare for children. These findings are important to consider when planning for potential future public health emergencies but also in the wider context of encouraging appropriate use of urgent healthcare.
Erasing motion: Scrambling direction selectivity in visual cortex during saccades
Authors: Miura Satoru K. , Scanziani Massimo 
Published: March 2021

AbstractDistinguishing sensory stimuli caused by changes in the environment from those caused by an animal’s own actions is a hallmark of sensory processing. Saccades are rapid eye movements that shift the image on the retina. How visual systems differentiate motion of the image induced by saccades from actual motion in the environment is not fully understood. Here, we discovered that in mouse primary visual cortex (V1), the two types of motion evoke distinct activity patterns. This is because during saccades, V1 combines the visual input with a strong non-visual input arriving from the thalamic pulvinar nucleus. Thus, the pulvinar input ensures differential V1 responses to external and self-generated motion and may allow the animal to interpret sensory stimuli within the context of its actions.
Multiple timescales in bacterial growth homeostasis
Authors: Stawsky Alejandro , Vashistha Harsh , Salman Hanna , Brenner Naama 
Published: March 2021

AbstractIn balanced exponential growth, bacterial cells maintain the stability of multiple properties simultaneously: cell size, growth rate, cycle time and more. These are not independent but strongly coupled variables; it is nota-prioriclear which are under direct regulation and which are stabilized as a by-product of interactions. Here, we address this problem by separating different timescales in bacterial single-cell dynamics. Disentangling homeostatic set-points from fluctuations around them, we find that some properties have flexible set-points that highly sensitive to environment - defining “sloppy” variables, while other set-points are buffered and held tightly controlled - “stiff” variables. These control variables are combinations of sloppy ones that compensate one another over long times, creating a hierarchical buffering that protects them from environmental perturbations. This is manifested geometrically as a control manifold in the space of growth and division variables, whose in-plane directions span sloppy variables, while out-of-plane deviations are highly constrained. Cell size is found to be a sloppy variable, which is coupled to growth and division only on the short, single-cycle timescale. Our results show that cellular homeostasis involves multi-level regulation operating on multiple timescales. More generally, our work offers a data-driven approach for identifying control variables in a multi-dimensional system that can be applicable also in other contexts.
The ascending arousal system shapes low-dimensional neural dynamics to mediate awareness of intrinsic cognitive states
Authors: Munn Brandon , Müller Eli J. , Wainstein Gabriel , Shine James M. 
Published: March 2021

AbstractModels of cognitive function typically focus on the cerebral cortex and hence overlook functional links to subcortical structures. This view neglects the highly-conserved ascending arousal system’s role and the computational capacities it provides the brain. In this study, we test the hypothesis that the ascending arousal system modulates cortical neural gain to alter the low-dimensional energy landscape of cortical dynamics. Our analyses of spontaneous functional magnetic resonance imaging data and phasic bursts in both locus coeruleus and basal forebrain demonstrate precise time-locked relationships between brainstem activity, low-dimensional energy landscapes, network topology, and spatiotemporal travelling waves. We extend our analysis to a cohort of experienced meditators and demonstrate locus coeruleus-mediated network dynamics were associated with internal shifts in conscious awareness. Together, these results present a novel view of brain organization that highlights the ascending arousal system’s role in shaping both the dynamics of the cerebral cortex and conscious awareness.
TGIF1is required for chicken ovarian cortical development and generation of the juxtacortical medulla
Authors: Estermann Martin Andres , Hirst Claire Elizabeth , Major Andrew Thomas , Smith Craig Allen 
Published: March 2021

ABSTRACTDuring early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells; Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the transcription factor geneTGIF1for ovarian development in the chicken embryo.TGIF1is expressed in the two principal ovarian somatic cell populations, the cortex and the pre-granulosa cells of the medulla.TGIF1expression is associated with an ovarian phenotype in sex reversal experiments. In addition, targeted over-expression and gene knockdown experiments indicate that TGIF1 is required for proper ovarian cortical formation.TGIF1is identified as the first known regulator of juxtacortical medulla formation. These findings provide new insights into chicken ovarian differentiation and development, specifically in the process of cortical and juxtacortical medulla formation, a poorly understood area.SUMMARY STATEMENTThe transcription factor TGIF1 is required for proper ovarian sex differentiation in chicken embryos, regulating development of the cortical and juxtacortical medulla, independently of the supporting cell sex lineage.
A morpho-transcriptomic map of brassinosteroid action in the Arabidopsis root
Authors: Graeff Moritz , Rana Surbhi , Wendrich Jos R. , Dorier Julien , Eekhout Thomas , Fandino Ana Cecilia Aliaga , Guex Nicolas , Bassel George W. , De Rybel Bert , Hardtke Christian S. 
Published: March 2021

ABSTRACTThe effects of brassinosteroid signaling on shoot and root development have been characterized in great detail but did not identify a simple consistent positive or negative impact on a basic cellular parameter that would comprehensively explain the phenotype of brassinosteroid-related mutants. Here we combined digital 3D single-cell shape analysis and single-cell mRNA sequencing to characterize root meristems and mature root segments of brassinosteroid-blind mutants and wildtype. These data demonstrate that brassinosteroid signaling neither affects cell volume nor cell proliferation capacity. Instead, brassinosteroid signaling is essential for the precise orientation of cell division planes and the extent and timing of anisotropic cell expansion. Moreover, we found that the cell-aligning effects of brassinosteroid signaling can propagate to normalize the anatomy of both adjacent and distant brassinosteroid-blind cells through non-cell-autonomous functions, which are sufficient to restore overall root growth vigor. Finally, single-cell transcriptome data discern directly brassinosteroid-responsive genes from genes that can react to non-cell-autonomous brassinosteroid-dependent signals and highlight arabinogalactans as sentinels of brassinosteroid-dependent anisotropic cell expansion.
Ultra-deep whole genome bisulfite sequencing reveals a single methylation hotspot in human brain mitochondrial DNA
Authors: Guitton Romain , Dölle Christian , Alves Guido , Tysnes Ole-Bjørn , Nido Gonzalo S. , Tzoulis Charalampos 
Published: March 2021

ABSTRACTWhile DNA methylation is established as a major regulator of gene expression in the nucleus, the existence of mitochondrial DNA (mtDNA) methylation remains controversial. Here, we characterised the mtDNA methylation landscape in the prefrontal cortex of neurological healthy individuals (n=26) and patients with Parkinson’s disease (n=27), using a combination of whole genome bisulfite sequencing (WGBS) and bisulfite-independent methods. Accurate mtDNA mapping from WGBS data required alignment to an mtDNA reference only, to avoid misalignment to nuclear mitochondrial pseudogenes. Once correctly aligned, WGBS data provided ultra-deep mtDNA coverage (16,723±7,711), and revealed overall very low levels of cytosine methylation. The highest methylation levels (5.49±0.97%) were found on CpG position m.545, located in the heavy-strand promoter 1 region. The m.545 methylation was validated using a combination of methylation-sensitive DNA digestion and quantitative PCR analysis. We detected no association between mtDNA methylation profile and Parkinson’s disease. Interestingly, m.545 methylation correlated with the levels of mtDNA transcripts, suggesting a putative role in regulating mtDNA gene expression. In addition, we propose a robust framework for methylation analysis of mtDNA from WGBS data, which is less prone to false-positive findings due to misalignment of nuclear mitochondrial pseudogene sequences.Graphical abstract of the analyses and main findingsFresh-frozen brain tissue was obtained from the prefrontal cortex (Brodmann area 9) of 53 individuals, comprising 27 patients with idiopathic PD and 26 healthy controls. Tissue from the same samples was used in three different downstream analyses. WGBS was conducted on all 53 samples and the data were analysed using three different alignment strategies. Alignment against an mtDNA reference only was clearly superior as it gave the highest and most even depth of coverage. WGBS analysis revealed that mtDNA harbours very low levels of cytosine methylation, with the exception of the CpG position m.545 within the HSP1 region (lower right inset). The m.545 methylation was confirmed by bisulfite- and sequencing-independent methods, employing methylation-specific MspJI DNA digestion, followed by quantification with qPCR or fluorescent PCR and capillary electrophoresis. Finally, mtDNA transcript levels were determined by RT-qPCR and correlated to m.545 methylation levels, showing a positive association.
Depleting Hypothalamic Somatostatinergic Neurons Recapitulates Diabetic Phenotypes in Brain, Bone Marrow, Adipose, and Retina
Authors: Huang Chao , Rosencrans Robert Follett , Bugescu Raluca , Vieira Cristiano P. , Hu Ping , Adu-Agyeiwaah Yvonne , Gamble Karen L , Longhini Ana Leda F. , Fuller Patrick M , Leinninger Gina M. , Grant Maria B. 
Published: March 2021

AbstractHypothalamic inflammation and sympathetic nervous system hyperactivity are hallmark features of metabolic syndrome and type 2 diabetes. Hypothalamic inflammation may aggravate metabolic and immunologic pathologies due to extensive sympathetic activation of peripheral tissues. Loss of somatostatinergic (SST) neurons may contribute to enhanced hypothalamic inflammation. The present data show that leptin receptor deficient (db/db) mice exhibit reduced hypothalamic somatostatinergic cells, particularly in the periventricular nucleus. We model this finding, using adeno-associated virus (AAV) delivery of diphtheria toxin (DTA) driven by an SST-cre system to deplete these cells in SSTcre/gfpmice (SST-DTA). SST-DTA mice exhibit enhanced hypothalamic c-fos expression and brain inflammation as demonstrated by microglial and astrocytic activation. Bone marrow from SST-DTA mice undergoes skewed hematopoiesis, generating excess granulocyte-monocyte precursors and increased pro-inflammatory (CCR2hi) monocytes. Visceral adipose tissue from DTA-treated animals was resistant to catecholamine induced lipolysis. Finally, SST-DTA mice exhibited a “diabetic retinopathy like” phenotype: reduced visual function by optokinetic response and electroretinogram, as well as increased percentages of retinal monocytes. Importantly, hyperglycemia was not observed in SST-DTA mice. Thus, the isolated reduction in hypothalamic somatostatinergic neurons was able to recapitulate several hallmark features of type 2 diabetes in disease relevant tissues.