bluuebunny/crossref_metadata_2025_split huggingface dataset:
Debunking the “junk”: Unraveling the role of lncRNA–miRNA–mRNA networks in fetal hemoglobin regulation
Authors: Rahaman Motiur , Bhowmick Chiranjib , Komanapalli Jaikrishna , Mukherjee Mandrita , Byram Prasanna Kumar , Shukla Praphulla Chandra , Dolai Tuphan Kanti , Chakravorty Nishant 
Published: October 2021

AbstractFetal hemoglobin (HbF) induction is considered to be a promising therapeutic strategy to ameliorate the clinical severity of β-hemoglobin disorders, and has gained a significant amount of attention in recent times. Despite the enormous efforts towards the pharmacological intervention of HbF reactivation, progress has been stymied due to limited understanding of γ-globin gene regulation. In this study, we intended to investigate the implications of lncRNA-associated competing endogenous RNA (ceRNA) interactions in HbF regulation. Probe repurposing strategies for extraction of lncRNA signatures and subsequent in silico analysis on publicly available datasets (GSE13284, GSE71935 and GSE7874) enabled us to identify 46 differentially expressed lncRNAs (DElncRNAs). Further, an optimum set of 11 lncRNAs that could distinguish between high HbF and normal conditions were predicted from these DElncRNAs using supervised machine learning and a stepwise selection model. The candidate lncRNAs were then linked with differentially expressed miRNAs and mRNAs to identify lncRNA-miRNA-mRNA ceRNA networks. The network revealed that 2 lncRNAs (UCA1 and ZEB1-AS1) and 4 miRNAs (hsa-miR-19b-3p,hsa-miR-3646,hsa-miR-937 and hsa-miR-548j) sequentially mediate cross-talk among different signaling pathways which provide novel insights into the lncRNA-mediated regulatory mechanisms, and thus lay the foundation of future studies to identify lncRNA-mediated therapeutic targets for HbF reactivation.
A high content microscopy-based platform for detecting antibodies to the nucleocapsid, spike and membrane proteins of SARS-CoV-2
Authors: Williams Daniel M. , Hornsby Hailey , Shehata Ola M. , Brown Rebecca , Zafred Domen , Shun-Shion Amber S.M. , Hodder Anthony J. , Bliss Deepa , Metcalfe Andrew , Edgar James R. , Gordon David E. , Sayers Jon R. , Nicklin Martin J. , Collini Paul J. , Brown Steve , de Silva Thushan I. , Peden Andrew A. 
Published: October 2021

AbstractThe strong humoral immune response produced against the SARS-CoV-2 nucleocapsid (N) and spike (S) proteins has underpinned serological testing but the prevalence of antibody responses to other SARS-CoV-2 proteins, which may be of use as further serological markers, is still unclear. Cell-based serological screening platforms can fulfil a crucial niche in the identification of antibodies which recognise more complex folded epitopes or those incorporating post-translation modifications which may be undetectable by other methods used to investigate the antigenicity of the SARS-CoV-2 proteome. Here, we employed automated high content immunofluorescence microscopy (AHCIM) to assess the viability of such an approach as a method capable of assaying humoral immune responses against full length SARS-CoV-2 proteins in their native cellular state. We first demonstrate that AHCIM provides high sensitivity and specificity in the detection of SARS-CoV-2 N and S IgG. Assessing the prevalence of antibody responses to the SARS-CoV-2 structural membrane protein (M), we further find that 85% of COVID-19 patients within our sample set developed detectable M IgG responses (M sensitivity 85%, N sensitivity 93%, combined N + M sensitivity 95%). The identification of M as a serological marker of high prevalence may be of value in detecting additional COVID-19 cases during the era of mass SARS-CoV-2 vaccinations, where serological screening for SARS CoV-2 infections in vaccinated individuals is dependent on detection of antibodies against N. These findings highlight the advantages of using cell-based systems as serological screening platforms and raise the possibility of using M as a widespread serological marker alongside N and S.
Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), August-September 2021, the Netherlands
Authors: de Gier Brechje , Andeweg Stijn , Backer Jantien A. ,   RIVM COVID-19 surveillance and epidemiology team, Hahné Susan J.M. , van den Hof Susan , de Melker Hester E. , Knol Mirjam J. 
Published: October 2021

AbstractWe estimated vaccine effectiveness against onward transmission by comparing secondary attack rates among household members between vaccinated and unvaccinated index cases, based on source and contact tracing data collected when Delta variant was dominant. Effectiveness of full vaccination of the index against transmission to fully vaccinated household contacts was 40% (95% confidence interval (CI) 20-54%), which is in addition to the direct protection of vaccination of contacts against infection. Effectiveness of full vaccination of the index against transmission to unvaccinated household contacts was 63% (95%CI 46-75%). We previously reported effectiveness of 73% (95%CI 65-79%) against transmission to unvaccinated household contacts for the Alpha variant.
The SARS-CoV-2 infection among students in the University of Porto: a cross-sectional study
Authors: Meireles Paula , Costa Joana Pinto , João Novais Maria , Miranda Daniela , Lopes Mariana Mendes , Severo Milton , Barros Henrique 
Published: October 2021

ABSTRACTIntroductionIncidence based on notified cases of SARS-CoV-2 infection underestimates the real extension of the infection. We aimed to quantify SARS-CoV-2 specific antibodies’ seroprevalence among University students in Porto.MethodsA rapid point of care testing for SARS-CoV-2 specific immunoglobulin (Ig) M and IgG antibodies was performed, and a questionnaire was applied to the 6512 voluntary students from September to December 2020. We computed the apparent IgM, IgG and IgM or IgG prevalence, and the true prevalence and 95% credible intervals (95% CI) using Bayesian inference.ResultsWe found an apparent prevalence (IgM or IgG) of 9.7%, the true prevalence being 7.9% (95% CI 4.9-11.1). Prevalence was significantly higher among males (10.9% vs 9.2%), international students (18.1% vs 10.4% local vs 8.8% nationally displaced) and increased with age. Those with a known risk contact, that experienced quarantine, had symptoms, or a previous negative molecular test had a higher seroprevalence. Of the 91 (1.4%) students who reported a molecular diagnosis, 86.7% were reactive for IgM or IgG.ConclusionBased on immunological evidence infection was 5.6 times more frequent than if based on a molecular diagnosis. The higher seroprevalence among male, older, and international students emphasizes the importance of identifying particular groups.
Modelling airborne transmission of SARS-CoV-2 using CARA: Risk assessment for enclosed spaces
Authors: Henriques Andre , Mounet Nicolas , Aleixo Luis , Elson Philip , Devine James , Azzopardi Gabriella , Andreini Marco , Rognlien Markus , Tarocco Nicola , Tang Julian 
Published: October 2021

AbstractThe global crisis triggered by the COVID-19 pandemic has highlighted the need for a proper risk assessment of respiratory pathogens in indoor settings. This paper documents the COVID Airborne Risk Assessment (CARA) methodology, to assess the potential exposure of airborne SARS-CoV-2 viruses, with an emphasis on the effect of certain virological and immunological factors in the quantification of the risk. The proposed model is the result of a multidisciplinary approach linking physical, mechanical and biological domains, benchmarked with clinical and experimental data, enabling decision makers or facility managers to perform risk assessments against airborne transmission. The model was tested against two benchmark outbreaks, showing good agreement. The tool was also applied to several everyday-life settings, in particular for the cases of a shared office, classroom and ski cabin. We found that 20% of infected hosts can emit approximately 2 orders of magnitude more viral-containing particles, suggesting the importance of super-emitters in airborne transmission. The use of surgical-type masks provides a 5-fold reduction in viral emissions. Natural ventilation through the opening of windows at all times are effective strategies to decrease the concentration of virions and slightly opening a window in the winter has approximately the same effect as a full window opening during the summer. Although vaccination is an effective protection measure, non-pharmaceutical interventions, which significantly reduce the viral density in the air (ventilation, masks), should be actively supported and included early in the risk assessment process. We propose a critical threshold value approach which could be used to define an acceptable risk level in a given indoor setting.
COVID-19 testing in schools: Perspectives of school administrators, teachers, parents, and students in Southern California
Authors: Unger Jennifer B. , Soto Daniel W. , Lee Ryan , Deva Sohini , Shanker Kush , Sood Neeraj , Hu Howard 
Published: October 2021

ABSTRACTBackgroundSchool-based COVID-19 testing is a potential strategy to facilitate the safe reopening of schools that have been closed due to the pandemic. This qualitative study assessed attitudes toward this strategy among four groups of stakeholders: school administrators, teachers, parents, and high school students.MethodsFocus groups and interviews were conducted in Los Angeles from December 2020 to January 2021 when schools were closed due to the high level of COVID transmission in the community.ResultsFindings indicated similarities and differences in attitudes toward in-school COVID-19 testing. All groups agreed that frequent in-school COVID-19 testing could increase the actual safety and perceived safety of the school environment. School administrators and teachers expressed pessimism about the financial cost and logistics of implementing a testing program. Parents supported frequent testing but expressed concerns about physical discomfort and stigma for students who test positive. Teachers and parents noted that testing would prevent parents from sending sick children to school. Students were in favor of testing because it would allow them to return to in-person school after a difficult year of online learning.ConclusionIn-school COVID-19 testing could be a useful component of school reopening plans and will be accepted by stakeholders if logistical and financial barriers can be surmounted and stigma from positive results can be minimized.
Emergence of networks of shared restriction-modification systems in phage-bacteria ecosystems
Authors: Eriksen Rasmus Skytte , Malhotra Nitish , Narain Seshasayee Aswin Sai , Sneppen Kim , Krishna Sandeep 
Published: October 2021

1AbstractRestriction-modification (RM) systems are the most ubiquitous bacterial defense system against bacteriophages and an important part of controlling phage predation. Using genomic sequence data, we show that RM systems are often shared among bacterial strains in a structured way. Examining the network of interconnections between bacterial strains within each genus, we find that in many genera strains share more RM systems than expected from a random network. We also find that many genera have a larger than expected number of bacterial strains with unique RM systems. We use population dynamics models of closed and open phage-bacteria ecosystems to qualitatively understand the selection pressures that could lead to these non-random network structures with enhanced overlap or uniqueness. In our models we find that the phages impose a pressure that favours bacteria with more RM systems, and more overlap of RM systems with other strains, but in bacteria dominated states this is opposed by the increased cost to the growth rate of these bacteria. Similar to what we observe in the genome data, we find that two distinct bacterial strategies emerge – strains either have a larger overlap than expected, or they have more unique RM systems than one expects from a null model. The former strategy appears to dominate when the repertoire of available RM systems is smaller but the average number of RM systems per strain is larger.
Actin dynamics regulation by TTC7A/PI4KIIIα axis limits DNA damage and cell death during leukocyte migration
Authors: Gajardo Tania , Lô Marie , Bernard Mathilde , Leveau Claire , El-Daher Marie-Thérèse , Kurowska Mathieu , Lay Gregoire Le , Moshous Despina , Neven Bénédicte , Fischer Alain , Ménasché Gaël , de Saint Basile Geneviève , Vargas Pablo , Sepulveda Fernando E. 
Published: October 2021

AbstractThe actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cell processes, including cell migration. Mutations in the TTC7A gene have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. Although several cellular functions have been associated with TTC7A, the role of the protein in the maintenance of the immune homeostasis is still poorly understood. Here we leverage microfabricated devices to investigate the impact of TTC7A deficiency in leukocytes migration at the single cell level. We show that TTC7A-deficient leukocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositides signaling, leading to the downregulation of the PI3K/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamic. This resulted in impaired cell motility, accumulation of DNA damage and increased cell death during chemotaxis in dense 3D gels. Our results highlight a novel role of TTC7A as a critical regulator of leukocyte migration. Impairment of this cellular function is likely to contribute to pathophysiology underlying progressive immunodeficiency in patients.
Pleiotropic and Non-redundant Effects of an Auxin Importer in Setaria and Maize1
Authors: Zhu Chuanmei , Box Mathew S. , Thiruppathi Dhineshkumar , Hu Hao , Yu Yunqing , Doust Andrew N. , McSteen Paula , Kellogg Elizabeth A. 
Published: October 2021

ABSTRACTDirectional transport of auxin is critical for inflorescence and floral development in flowering plants, but the role of auxin influx carriers (AUX1 proteins) has been largely overlooked. Taking advantage of available AUX1 mutants in Setaria viridis and maize, we uncover previously unreported aspects of plant development that are affected by auxin influx, including higher order branches in the inflorescence, stigma branch number, and glume (floral bract) development, and plant fertility. However, disruption of auxin flux does not affect all parts of the plant, with little obvious effect on inflorescence meristem size, time to flowering, and anther morphology. In double mutant studies in maize, disruptions of ZmAUX1 also affect vegetative development. A GFP-tagged construct of SvAUX1 under its native promoter showed that the AUX1 protein localizes to the plasma membrane of outer tissue layers in both roots and inflorescences, and accumulates specifically in inflorescence branch meristems, consistent with the mutant phenotype and expected auxin maxima. RNA-seq analysis finds that most gene expression modules are conserved between mutant and wildtype plants, with only a few hundred genes differentially expressed in spp1 inflorescences. Using CRISPR-Cas9 technology, we disrupted SPP1 and the other four AUX1 homologs in S. viridis. SvAUX1/SPP1 has a larger effect on inflorescence development than the others, although all contribute to plant height, tiller formation, leaf, and root development. The AUX1 importers are thus not fully redundant in S. viridis. Our detailed phenotypic characterization plus a stable GFP-tagged line offer tools for future dissection of the function of auxin influx proteins.One sentence summaryMutations in a single auxin importer gene Spp1/SvAUX1 uncover broad and unexpected effects in nearly all aspects of the development of shoots, inflorescences, and flowers.
Efficient incorporation and template-dependent polymerase inhibition are major determinants for the broad-spectrum antiviral activity of remdesivir
Authors: Gordon Calvin J. , Lee Hery W. , Tchesnokov Egor P. , Perry Jason K. , Feng Joy Y. , Bilello John P. , Porter Danielle P. , Götte Matthias 
Published: October 2021

AbstractRemdesivir (RDV) is a direct antiviral agent that is approved in several countries for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RDV exhibits broad-spectrum antiviral activity against positive-sense RNA viruses, e.g., SARS-CoV-2 and hepatitis C virus (HCV) and non-segmented negative-sense RNA viruses, e.g., Nipah virus (NiV), while several segmented negative-sense RNA viruses such as influenza (Flu) virus or Crimean-Congo hemorrhagic fever virus (CCHFV) are not sensitive to the drug. The reasons for this apparent pattern are unknown. Here, we expressed and purified representative RNA-dependent RNA polymerases (RdRp) and studied three biochemical parameters that have been associated with the inhibitory effects of RDV-triphosphate (TP): (i) selective incorporation of the nucleotide substrate RDV-TP, (ii) the effect of the incorporated RDV-monophosphate (MP) on primer extension, and (iii) the effect of RDV-MP in the template during incorporation of the complementary UTP. The results of this study revealed a strong correlation between antiviral effects and efficient incorporation of RDV-TP. Delayed chain-termination is heterogeneous and usually inefficient at higher NTP concentrations. In contrast, template-dependent inhibition of UTP incorporation opposite the embedded RDV-MP is seen with all polymerases. Molecular modeling suggests a steric conflict between the 1’-cyano group of RDV-MP and conserved residues of RdRp motif F. We conclude that future efforts in the development of nucleotide analogues with a broader spectrum of antiviral activities should focus on improving rates of incorporation while capitalizing on the inhibitory effects of a bulky 1’-modification.
Ionic strength modulates HU protein-induced DNA supercoiling
Authors: Zhang Alexander , Yan Yan , Leng Fenfei , Dunlap David , Finzi Laura 
Published: October 2021

AbstractThe histone-like protein from E. coli strain U93 (HU) is an abundant nucleoid-associated protein that contributes to the compaction of the bacterial genome as well as to the regulation of many of its transactions. Despite many years of investigations, the way and extent to which HU binding alters the DNA double helix and/or generates hierarchical structures using DNA as a scaffold is not completely understood. Here we combined single-molecule magnetic measurements with circular dichroism studies to monitor structural changes in the DNA-HU fiber as HU concentration was increased from 0 to 1000 nM under low and physiological monovalent salt conditions. We confirmed that DNA compaction correlated with HU concentration in a biphasic manner but DNA unwinding varied monotonically with HU concentration in 100 mM KCl. Instead, in more physiological 200 mM salt conditions, DNA compaction was monotonic while HU-induced DNA unwinding was negligible. Differential compaction and unwinding of DNA may be part of the response of bacteria to large variations in salt concentrations.
Modular Derivation and Unbiased Single-cell Analysis of Regional Human Hindbrain And Spinal Neurons Enables Discovery of Nuanced Transcriptomic Patterns along Developmental Axes
Authors: Iyer Nisha R. , Shin Junha , Cuskey Stephanie , Tian Yucheng , Nicol Noah R. , Doersch Tessa E. , McCalla Sunnie Grace , Roy Sushmita , Ashton Randolph S. 
Published: October 2021

SummaryOur inability to derive the vast neuronal diversity of the posterior central nervous system (pCNS) using human pluripotent stem cells (hPSCs) poses a major impediment to understanding human neurodevelopment and disease in the hindbrain and spinal cord. Here we establish a modular differentiation paradigm that recapitulates patterning along both the rostrocaudal (R/C) and dorsoventral (D/V) axes of the pCNS, enabling derivation of any neuronal phenotype with discrete regional specificity. First, neuromesodermal progenitors (NMPs) with discrete Hox profiles are efficiently converted to pCNS progenitors (pCNSPs). Then by tuning D/V signaling, pCNSPs are directed to ventral Shh-dependent MNs (MNs) and locomotor interneurons (INs) or dorsal TGF-β-dependent proprioceptive INs and TGF-β-independent sensory INs. We applied D/V protocols to NMPs spanning the R/C axis for expansive single-cell RNA-sequencing (scRNAseq) analysis. By implementing a novel computational pipeline comprising sparse non-negative matrix factorization, consensus clustering, and combinatorial gene expression pattern identification, we detect hundreds of transcriptional markers within region-specific neuronal phenotypes, enabling discovery of gene expression patterns along the developmental axes. These findings highlight the potential of these resources to advance a mechanistic understanding of pCNS development, expand the potential and accuracy of in vitro models, and inform novel regenerative therapeutic strategies.
Understanding the contexts and mechanisms of bluespace prescription programmes implemented in health and social care settings: a realist review
Authors: Alejandre Julius Cesar , Chastin Sebastien , Irvine Katherine N. , Georgiou Michail , Khanna Preeti , Tieges Zoë , Smith Niamh , Chong Yong-Yee , Onagan Frances Claire , Price Lesley , Pfleger Sharon , Helliwell Rachel , Singleton Judith , Curran Samuel , Helwig Karin 
Published: October 2021

AbstractBackgroundNature-based social prescribing programmes such as ‘bluespace prescription’ may promote public health and health improvement of individuals with long-term conditions. However, there is limited systematically synthesised evidence that investigates the contexts and mechanisms of Bluespace Prescription Programmes (BPPs) that could inform programme theories for policy and practice.MethodsWe conducted a realist review by searching six databases for articles published between January 2000 and February 2020, in English, about health and social care professionals providing referral to or prescription of blue space activities with health-related outcomes. We developed themes of contextual factors by analysing the contexts of BPPs. We used these contextual factors to develop programme theories describing the mechanisms of BPP implementation. Our study was registered with PROSPERO (CRD42020170660).ResultsFifteen studies with adequate to strong quality were included from 6,736 records. Service users had improvements on their physical, mental, social health, and environmental knowledge after participating in BPPs referred to or prescribed by health and social care professionals. Patient-related contextual factors were referral information, free equipment and transportation, social support, blue space environments, and skills of service providers. Programme-related contextual factors were communication, multi-stakeholder collaboration, financing, and adequate service providers. Programme theories on patient enrolment, engagement, adherence, communication protocols, and long-term programme sustainability described the mechanisms of BPP implementation.ConclusionBPPs could support health and social care services if contextual factors and mechanisms of programme theories associated with patients and programme delivery are considered for implementation. Our findings have implications in planning, development, and implementation of similar nature-based social prescribing programmes in health and social care settings.