bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsupervised Clustering characterizes the CPG dinucleotides distribution of the Andes hantavirus
Authors: Mastriani Emilio , Liu Shu-Lin 
Published: February 2021

AbstractHantaviruses belong to the family ofBunyaviridae, and small mammals host them. Humans are infected either by inhaling virus-containing aerosols or through contact with animal droppings. Even if rodents host the pathogenic species and humans are dead-end hosts, they get accidentally infected. Andes Orthohantavirusus (ANDV) seems to be the only species with documented person-to-person transmission. Hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are both serious syndromes associated with hantavirus infections. For both syndromes, the mortality rate is near 40%. Decades of studies already highlighted the CpG repression in RNA viruses, and both the estimation of the CpG odds ratio and the correlation with their genome polarity were dominant factors to figure out the CpG bias. We conducted the differential analysis of the CpG odds ratio for all the orthohantaviruses on the full segmented genomes (L, M, S). The results suggested the statistical significance of the three groups. The“Small”genomes resulted in the more informative from the CpG odd ratio point of view. We calculated the CpG odds ratio for all the Orthohantaviruses within these segments, and besides, we estimated the correlation coefficient with the relative coding sequences (CDS). Preliminary results firstly confirmed the CpG odds ratio as the lowest among all the nucleotides. Second, highlighted the Andes virus as that whose CpG odds ratio within CDS is highest. The use of these two measures as features for unsupervised clustering algorithms has brought to the identification of four different sub-groups inside of theOrthohantaviridaefamily. The evidence is that the Andes Hantavirus exhibits a peculiar CpG odds ratio distribution, probably linked to its unique prerogative to pass from human-to-human.
Development of Tribo-Electroceutical Fabrics for Potential Application in Self-sanitizing Personal Protective Equipment (PPE)
Authors: Bayan Sayan , Adhikari Aniruddha , Pal Uttam , Ghosh Ria , Mondal Susmita , Darbar Soumendra , Saha-Dasgupta Tanusri , Ray Samit Kumar , Pal Samir Kumar 
Published: February 2021

AbstractAttachment of microbial bodies including coronavirus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a novel tribo-electroceutical fabric (TECF) consisting of commonly available materials namely Nylon, and Silicone Rubber (SR) for the fabrication of protective gloves on Nitrile platform, as a model wearable PPE. A small triboelectric device (2 cm × 2 cm) consisting of SR and Nylon on Nitrile can generate more than 20 volt transient or 41 µW output power, which is capable of charging a capacitor up to 65 V in only ∼50 sec. The novelty of the present work relies on the TECF led anti-microbial activity through the generation of an electric current in saline water. The fabrication of TECF based functional prototype gloves can generate hypochlorite ions through the formation of electrolysed water upon rubbing them with saline water. Further a computational modelling has been employed to reveal the optimum structure and mechanistic pathway of anti-microbial hypochlorite generation. Detailed anti-microbial assays have been performed to establish effectiveness of such TECF based gloves to reduce the risk from life threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other material with comparable properties, as material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19.
Effect of in-hospital treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on mortality and complications in patients hospitalized for COVID-19: a large Spanish cohort study
Authors: Roy-Vallejo Emilia , Sánchez Purificación Aquilino , Torres Peña José David , Sánchez Moreno Beatriz , Arnalich Francisco , García Blanco María José , Miranda José López , Cabrera Juan Luis Romero , Gil Carmen Rosario Herrero , Bascunana J , Rubio-Rivas Manuel , Otero Sara Pintos , Sempere Verónica Martínez , Rodríguez-Solís Jesús Ballano , Sánchez Ricardo Gil , del Pino Jairo Luque , González Noya Amara , Navas-Alcántara MS , Rodríguez Begoña Cortés , Alcalá José N. , Suárez-Lombraña Ana , Andrés Soler Jorge , Gómez Huelgas Ricardo , Casas Rojo José Manuel , Núñez-Cortés Jesús Millán ,   for the SEMI-COVID-19 Network^
Published: February 2021

AbstractBackgroundThe use of ACEI (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin II Receptor Blocker) in COVID-19 remains controversial. Our main aim was to describe the effect of ACEI/ARB treatment during COVID-19 hospitalization on mortality and complications.MethodsRetrospective, observational, multicenter study, part of the SEMI-COVID-19 Registry, comparing patients with COVID-19 treated with ACEI/ARB during hospitalization to those not treated. The primary endpoint was incidence of the composite outcome of prognosis (IMV [Invasive Mechanical Ventilation], NIMV [Non-Invasive Mechanical Ventilation], ICU admission [Intensive Care Unit], and/or all-cause mortality). The secondary endpoint was incidence of MACE (Major Adverse Cardiovascular Events). We evaluated both outcomes in patients whose treatment with ACEI/ARB continued or was withdrawn during hospitalization.ResultsBetween February and June 2020, 11,205 patients were included, with mean age 67 years (SD=16.3) and 43.1% female; 2,162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed a protective effect on all-cause mortality (p<.0001). In hypertensive patients it was also protective in terms of IMV, ICU admission, and the composite outcome of prognosis (p<.0001 for all). No differences were found in incidence of MACE. Patients previously treated with ACEI/ARB who continued treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB had a more beneficial effect on survival than ACEI (HR 0.77, 95%CI 0.62-0.96).ConclusionACEI/ARB treatment during COVID-19 hospitalization had a protective effect on mortality. The benefits were greater in hypertensive patients, those who continued treatment during hospitalization, and those taking ARB.SummaryTreatment with ACEI/ARB during COVID-19 hospitalization showed a beneficial effect on mortality in the general population. The benefit was greater in hypertensive patients, in those who maintained treatment during hospitalization and those taking ARB.
Longitudinal high-resolution imaging through a flexible intravital imaging window
Authors: Jacquemin Guillaume , Benavente-Diaz Maria , Djaber Samir , Bore Aurélien , Dangles-Marie Virginie , Surdez Didier , Tajbakhsh Shahragim , Fre Silvia , Lloyd-Lewis Bethan 
Published: February 2021

AbstractIntravital microscopy (IVM) is a powerful technique that enables imaging of internal tissues at (sub)cellular resolutions in living animals. Here, we present a silicone-based imaging window consisting of a fully flexible, suture-less design that is ideally suited for long-term, longitudinal IVM of growing tissues and tumors. Crucially, we show that this window, without any customization, is suitable for numerous anatomical locations in mice using a rapid and standardized implantation procedure. This low-cost device represents a substantial technological and performance advance that facilitates intravital imaging in diverse contexts in higher organisms, opening new avenues forin vivoimaging of soft and fragile tissues.One-sentence summaryThis study presents a versatile, fully flexible imaging window that acts as an implantable transparent ‘second skin’ for small laboratory animalin vivoimaging.
More comprehensive proprioceptive stimulation of the hand amplifies its cortical processing
Authors: Hakonen Maria , Nurmi Timo , Vallinoja Jaakko , Jaatela Julia , Piitulainen Harri 
Published: February 2021

ABSTRACTCorticokinematic coherence (CKC) quantifies the phase coupling between limb kinematics and cortical neurophysiological signals reflecting proprioceptive feedback to the primary sensorimotor (SM1) cortex. We studied CKC to proprioceptive stimulation (i.e. movement-actuator-evoked movements) of right-hand digits (index, middle, ring and little) performed simultaneously or separately. CKC was computed between magnetoencephalography (MEG) and finger acceleration signals. The strongest CKC was obtained by stimulating the fingers simultaneously at fixed 3-Hz frequency, and can, therefore, be recommended as design for fast functional localization of the hand area in the primary sensorimotor (SM1) cortex using MEG. The peaks of CKC sources were concentrated in the hand region of the SM1 cortex, but did not follow consistent somatotopic order. This result suggests that spatial specificity of MEG is not sufficient to separate proprioceptive finger representations of the same hand adequately or that their representations are overlapping.
Outcomes of Progranulin Gene Therapy in the Retina are Dependent on Time of Delivery
Authors: Zin Emilia A. , Han Daisy , Tran Jennifer , Morisson-Welch Nikolas , Visel Meike , Kuronen Mervi , Flannery John G. 
Published: February 2021

AbstractNeuronal ceroid lipofuscinosis (NCL) is a family of neurodegenerative diseases caused by mutations to genes related to lysosomal function. One variant, CNL11, is caused by mutations to the gene encoding the protein progranulin. Primarily secreted by microglia, progranulin regulates neuronal lysosomal function once endocytosed. Absence of progranulin causes cerebellar atrophy, seizures, ataxia, dementia and vision loss. As progranulin gene therapies targeting the brain are developed, it is also advantageous to focus on the retina, as its characteristics are beneficial for gene therapy development: the retina is easily visible through direct imaging, can be assessed through quantitative methodsin vivo, requires smaller amounts of AAV and AAV can be administered via a less invasive surgery. In this study we characterize the retinal degeneration in a progranulin knockout mouse model of CLN11 and study the effects of gene replacement at different time points. All mice heterologously expressing progranulin showed reduction in lipofuscin deposits and microglia infiltration. While mice that receive systemic AAV9.2YF-scCAG-PGRN at post-natal day 3 or 4 show a reduction in retina thinning, mice injected intravitreally at months 1 and 6 with 7m8-scCAG-PGRN show no improvement, and mice injected at 12 months of age show increased retinal thinning in comparison to their controls. Thus, delivery of progranulin proves to be time-sensitive, requiring early administration for optimal therapeutic benefit.
Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape
Authors: Brown Jonathan C. , Goldhill Daniel H. , Zhou Jie , Peacock Thomas P. , Frise Rebecca , Goonawardane Niluka , Baillon Laury , Kugathasan Ruthiran , Pinto Andreia L. , McKay Paul F. , Hassard Jack , Moshe Maya , Singanayagam Aran , Burgoyne Thomas ,   the ATACCC Investigators,   PHE Virology Consortium, Barclay Wendy S. 
Published: February 2021

AbstractLineage B.1.1.7 (Variant of Concern 202012/01) is a new SARS-CoV-2 variant which was first sequenced in the UK in September 2020 before becoming the majority strain in the UK and spreading worldwide. The rapid spread of the B.1.1.7 variant results from increased transmissibility but the virological characteristics which underpin this advantage over other circulating strains remain unknown. Here, we demonstrate that there is no difference in viral replication between B.1.1.7 and other contemporaneous SARS-CoV-2 strains in primary human airway epithelial (HAE) cells. However, B.1.1.7 replication is disadvantaged in Vero cells potentially due to increased furin-mediated cleavage of its spike protein as a result of a P681H mutation directly adjacent to the S1/S2 cleavage site. In addition, we show that B.1.1.7 does not escape neutralisation by convalescent or post-vaccination sera. Thus, increased transmission of B.1.1.7 is not caused by increased replication, as measured on HAE cells, or escape from serological immunity.
A mouse model of occult intestinal colonization demonstrating antibiotic-induced outgrowth of carbapenem-resistantEnterobacteriaceae
Authors: Sim Choon K. , Kashaf Sara Saheb , Conlan Sean , Stacy Apollo , Proctor Diana M. , Almeida Alexandre , Bouladoux Nicolas , Chen Mark ,   NISC Comparative Sequencing Program, Finn Robert D. , Belkaid Yasmine , Segre Julia A. 
Published: February 2021

AbstractBackgroundThe human intestinal microbiome is a complex community that contributes to host health and disease. In addition to normal microbiota, pathogens like carbapenem-resistantEnterobacteriaceaemay be asymptomatically present. When these bacteria are present at very low levels, they are often undetectable in hospital surveillance cultures, known as occult or subclinical colonization. Through the use of antibiotics, these subclinical pathogens can increase to sufficiently high levels to become detectable, in a process called outgrowth. However, little is known about the interaction between gut microbiota andEnterobacteriaceaeduring occult colonization and outgrowth.ResultsWe developed a clinically relevant mouse model for studying occult colonization. Conventional wild-type mice without antibiotic pre-treatment were exposed toK. pneumoniaebut rapidly tested negative for colonization. This occult colonization was found to perturb the microbiome as detected by both 16S rRNA amplicon and shotgun metagenomic sequencing. Outgrowth of occultK. pneumoniaewas induced either by a four-antibiotic cocktail or by individual receipt of ampicillin, vancomycin or azithromycin, which all reduced overall microbial diversity. Notably, vancomycin was shown to triggerK. pneumoniaeoutgrowth in only a subset of exposed animals (outgrowth-susceptible). To identify factors that underlie outgrowth susceptibility, we analyzed microbiome-encoded gene functions and were able to classify outgrowth-susceptible microbiomes using pathways associated with mRNA stability. Lastly, an evolutionary approach illuminated the importance of xylose metabolism inK. pneumoniaecolonization, supporting xylose abundance as a second susceptibility indicator. We showed that our model is generalizable to other pathogens, including carbapenem-resistantEscherichia coliandEnterobacter cloacae.ConclusionsThis study suggests that microbiota mRNA and small-molecule metabolites may be used to predict outgrowth-susceptibility. Our modeling of occult colonization and outgrowth could help the development of strategies to mitigate the risk of subsequent infection and transmission in medical facilities and the wider community.
Approximate Bayesian computation untangles signatures of contemporary and historical hybridization between two endangered species
Authors: Dittberner Hannes , Tellier Aurelien , de Meaux Juliette 
Published: February 2021

ABSTRACTContemporary gene flow, when resumed after a period of isolation, can have crucial consequences for endangered species, as it can both increase the supply of adaptive alleles and erode local adaptation. Determining the history of gene flow and thus the importance of contemporary hybridization, however, is notoriously difficult. Here, we focus on two endangered plant species,Arabis nemorensisandA. sagittata, which hybridize naturally in a sympatric population located on the banks of the Rhine. Using reduced genome sequencing, we determined the phylogeography of the two taxa but report only a unique sympatric population. Molecular variation in chloroplast DNA indicated thatA. sagittatais the principal receiver of gene flow. Applying classical D-statistics and its derivatives to whole-genome data of 35 accessions, we detect gene flow not only in the sympatric population but also among allopatric populations. Using an Approximate Bayesian computation approach, we identify the model that best describes the history of gene flow between these taxa. This model shows that low levels of gene flow have persisted long after speciation. Around 10 000 years ago, gene flow stopped and a period of complete isolation began. Eventually, a hotspot of contemporary hybridization was formed in the unique sympatric population. Occasional sympatry may have helped protect these lineages from extinction in spite of their extremely low diversity.
sweetD: An R package using Hoeffding’s D statistic to visualise the dependence between M and A for large numbers of gene expression samples
Authors: Barton Amber 
Published: February 2021

AbstractSummaryMA plots are frequently used to examine the relationship between gene abundance and differences in gene expression between two samples. In good quality samples without batch effects or outliers, there is generally no or little relationship between intensity and log fold difference. As the number of MA plots increases quadratically with the number of samples, for large datasets the number of potential MA plots becomes prohibitively high for manual examination. Here we present an R package calculating and visualising the dependence between abundance and log fold difference for large numbers of samples using Hoeffding’s D statistic.Availability and implementationsweetD is currently available as an R package on Githubhttps://github.com/amberjoybarton/sweetD.
Dynamic expression of smRNA from fecal exosome in disease progression of an inflammatory bowel disorder mouse model
Authors: Manning Sean , Torii Shisui , Atkins Hannah M , Kawasawa Yuka Imamura 
Published: February 2021

ABSTRACTInflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract affecting over 3 million adults in the United States. Despite being widespread, reliable early diagnostic tests are not available. We examined exosomal small RNA (smRNA), specifically targeting microRNA (miRNA) and piRNA from the stool samples of IBD model mice, interleukin 10 knockout mice (IL-10 KO), as a potential diagnostic marker. Stool samples were specifically chosen because they are readily available, and collection is noninvasive. At the end of the experimental period, the gastrointestinal (GI) tract was collected, and disease severity was scored. Histopathology showed a significant increase in inflammation and proliferation within the proximal and distal large intestines. smRNA profiles were examined upon conventional housing (start-point) which is a determinant factor of spontaneous IBD progression in the IL-10 KO mice, terminal illness (end-point), and 6 weeks before the end-point (mid-point), when the mice were still phenotypically healthy. We found 504 smRNA that were significantly differentially expressed between before symptom onset and terminal sedation. These changes were not detected in wild-type samples. Moreover, clustering analysis of expression changes over the disease progression identified a unique set of smRNAs that primarily target pro-inflammatory or anti-inflammatory genes. The expression of smRNAs that suppresses pro-inflammatory genes was higher at 6 weeks before terminal sedation, suggesting the downregulation of the pro-inflammatory genes advances the terminal illness of the IBD. In summary, our study proposes that fecal exosomal smRNA profiling offers a new opportunity to monitor the inflammatory status of the gut with a capability of detecting its pro-inflammatory (asymptomatic) status. Our next step is to understand the spatiotemporal interplay of these exosomes and the host cells in the gut as well as the complete biochemical makeup of fecal exosomes, such as mRNA, DNA, protein, and lipids. This will lead to an exciting development of reengineered exosomes that can be utilized to treat or even prevent the pro-inflammatory colonic lesion while the host is still clinically asymptomatic.
Morningness-eveningness assessment from mobile phone communication analysis
Authors: Roy Chandreyee , Monsivais Daniel , Bhattacharya Kunal , Dunbar Robin I.M. , Kaski Kimmo 
Published: February 2021

AbstractHuman behaviour follows a 24-hour rhythm and is known to be governed by the individual chronotypes. Due to the widespread use of technology in our daily lives, it is possible to record the activities of individuals through their different digital traces. In the present study we utilise a large mobile phone communication dataset containing time stamps of calls and text messages to study the circadian rhythms of anonymous users in a European country. After removing the effect of the synchronization of East-West sun progression with the calling activity, we used two closely related approaches to heuristically compute the chronotypes of the individuals in the dataset, to identify them as morning persons or “larks” and evening persons or “owls”. Using the computed chronotyes we showed how the chronotype is largely dependent on age with younger cohorts being more likely to be owls than older cohorts. Moreover, our analysis showed how on average females have distinctly different chronotypes from males. Younger females are more larkish than males while older females are more owlish. Finally, we also studied the period of low calling activity for each of the users which is considered as a marker of their sleep period during the night. We found that while “extreme larks” tend to sleep more than “extreme owls” on the weekends, we do not observe much variation between them on weekdays. In addition, we have observed that women tend to sleep even less than males on weekdays while there is not much difference between them on the weekends.