bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancient evolution of hepadnaviral paleoviruses and their impact on host genomes
Authors: Lytras Spyros , Arriagada Gloria , Gifford Robert J 
Published: March 2021

Abstract
Hepadnaviruses (family Hepadnaviviridae) are reverse-transcribing animal viruses that infect vertebrates. DNA sequences derived from ancient hepadnaviruses have been identified in the germline genome of numerous vertebrate species, and these ‘endogenous hepatitis B viruses’ (eHBVs) reveal aspects of the long-term coevolutionary relationship between hepadnaviruses and their vertebrate hosts. Here, we use a novel, data-oriented approach to recover and analyse the complete repertoire of eHBV elements in published animal genomes. We show that germline incorporation of hepadnaviruses is exclusive to a single vertebrate group (Sauria) and that the eHBVs contained in saurian genomes represent a far greater diversity of hepadnaviruses than previously recognized. Through in-depth characterization of eHBV elements, we establish the existence of four distinct subgroups within the genus Avihepadnavirus and trace their evolution through the Cenozoic Era. Furthermore, we provide a completely new perspective on hepadnavirus evolution by showing that the metahepadnaviruses (genus Metahepadnavirus) originated &gt;300 million years ago in the Paleozoic Era and have historically infected a broad range of vertebrates. We also show that eHBVs have been intra-genomically amplified in some saurian lineages, and that eHBVs located at approximately equivalent genomic loci have been acquired in entirely distinct germline integration events. These findings indicate that selective forces have favoured the accumulation of hepadnaviral sequences at specific loci in the saurian germline. Our investigation provides a range of new insights into the long-term evolutionary history of reverse-transcribing DNA viruses and shows that germline incorporation of hepadnaviruses has played a role in shaping the evolution of saurian genomes.
The evolutionary dynamics of endemic human coronaviruses
Authors: Jo Wendy K , Drosten Christian , Drexler Jan Felix 
Published: March 2021

Abstract
Community protective immunity can affect RNA virus evolution by selecting for new antigenic variants on the scale of years, exemplified by the need of annual evaluation of influenza vaccines. The extent to which this process termed antigenic drift affects coronaviruses remains unknown. Alike the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seasonal human coronaviruses (HCoV) likely emerged from animal reservoirs as new human pathogens in the past. We therefore analyzed the long-term evolutionary dynamics of the ubiquitous HCoV-229E and HCoV-OC43 in comparison with human influenza A virus (IAV) subtype H3N2. We focus on viral glycoprotein genes that mediate viral entry into cells and are major targets of host neutralizing antibody responses. Maximum likelihood and Bayesian phylogenies of publicly available gene datasets representing about three decades of HCoV and IAV evolution showed that all viruses had similar ladder-like tree shapes compatible with antigenic drift, supported by different tree shape statistics. Evolutionary rates inferred in a Bayesian framework were 6.5 × 10−4 (95% highest posterior density (HPD), 5.4–7.5 × 10−4) substitutions per site per year (s/s/y) for HCoV-229E spike (S) genes and 5.7 × 10−4 (95% HPD, 5–6.5 × 10−4) s/s/y for HCoV-OC43 S genes, which were about fourfold lower than the 2.5 × 10−3 (95% HPD, 2.3–2.7 × 10−3) s/s/y rate for IAV hemagglutinin (HA) genes. Coronavirus S genes accumulated about threefold less (P &lt; 0.001) non-synonymous mutations (dN) over time than IAV HA genes. In both IAV and HCoV, the average rate of dN within the receptor binding domains (RBD) was about fivefold higher (P &lt; 0.0001) than in other glycoprotein gene regions. Similarly, most sites showing evidence for positive selection occurred within the RBD (HCoV-229E, 6/14 sites, P &lt; 0.05; HCoV-OC43, 23/38 sites, P &lt; 0.01; IAV, 13/15 sites, P = 0.08). In sum, the evolutionary dynamics of HCoV and IAV showed several similarities, yet amino acid changes potentially representing antigenic drift occurred on a lower scale in endemic HCoV compared to IAV. It seems likely that pandemic SARS-CoV-2 evolution will bear similarities with IAV evolution including accumulation of adaptive changes in the RBD, requiring vaccines to be updated regularly, whereas higher SARS-CoV-2 evolutionary stability resembling endemic HCoV can be expected in the post-pandemic stage.
Multi-transcriptomic analysis points to early organelle dysfunction in human astrocytes in Alzheimer’s disease
Authors: Galea Elena , Weinstock Laura D. , Larramona-Arcas Raquel , Pybus Alyssa F. , Giménez-Llort Lydia , Escartin Carole , Wood Levi B. 
Published: March 2021

AbstractRecent single-nucleus RNA sequencing of astrocytes in postmortem Alzheimer’s disease (AD) samples is limited by the low number of sequenced astrocytes and small cohort sizes. We developed a systems biology approach to identify astrocytic genes in public large bulk AD transcriptomes. Brain cell specific gene clusters were generated from RNA sequencing data from isolated healthy human brain cells using cell-type enrichment scoring and clustering. Cell-specific gene clusters were localized in whole-brain transcriptomes from 766 subjects diagnosed with AD or mild cognitive impairment (MCI) from the Mount Sinai Hospital, the Mayo Clinic, and the Religious Order Study/Memory and Aging Project (ROSMAP). Gene clusters were organized into manually curated functional categories including astrocytic categories absent from existing platforms, such as perisynaptic astrocytic processes (PAP). Changes among subjects were determined by gene set variation analysis (GSVA) and principal component analysis (PCA). Hierarchical clustering revealed molecular heterogeneity in individuals with the same clinical diagnosis. Particularly in the Mayo Clinic and ROSMAP cohorts, over 50% of Controls presented the massive down-regulation of genes encoding synaptic proteins typical of AD, whereas 30% of AD patients presented Control-like transcriptomic profiles. According to GSVA and PCA, down-regulation of neuronal genes related to synaptic proteins correlated with down-regulation of astrocytic genes encoding mitochondrial and endolysosomal proteins, and up-regulation of genes related to PAP. Transcriptomic data thus unravel a deep phenotypic transformation of human astrocytes in AD, affecting organelles and astrocyte-neuron interactions. We posit that therapies preventing organelle dysfunction in astrocytes may protect neural circuits in preclinical and clinical AD.Main pointsTranscriptomes of control subjects and AD patients segregate in two main molecular profiles regardless of clinical diagnosis.Dysregulation of the endolysosomal/mitochondrial axis in astrocytes correlates with impaired synaptic plasticity in neurons.
Impact of Vaccine Failure on the Transmission Dynamics of Measles in Nigeria
Authors: Nwankwo Ann , Iboi Enahoro. , Okuonghae Daniel 
Published: March 2021

AbstractMeasles is a vaccine preventable disease. However, it is still a major public health challenge in Nigeria.We therefore formulate a mathematical model for the transmission of measles with a two dose vaccination strategy and weaning of vaccine derived immunity. Using weekly measles cases for Nigeria in 2020 from the Nigeria Center for Disease Control (NCDC), the model was validated. This modelling study via numerical simulations showed that there is a possibility of disease control with a ten fold increase in the vaccination rates. Also, it was shown that primary vaccine failure has more impact on disease dynamics than secondary vaccine failure. Thus control strategies should not just focus on increase the vaccination rates but also look at measures that will help in reducing primary vaccine failure.
Successful incorporation of a genetic risk prediction research platform into routine newborn screening
Authors: Bendor-Samuel Owen M , Wishlade Tabitha , Willis Louise , Aley Parvinder , Choi Edward , Craik Rachel , Mujadidi Yama , Mounce Ginny , Roseman Fenella , De La Horra Gozalo Arancha , Bland James , Taj Nazia , Smith Ian , Ziegler Anette-Gabriele , Bonifacio Ezio , Winkler Christiane , Haupt Florian , Todd John A. , Servais Laurent , Snape Matthew D , Vatish Manu ,   the GPPAD Study Group
Published: March 2021

ABSTRACTAn increasing number of diseases can be offered treatments that are transformative if administered in a timely manner. However, many of these diseases are currently not included in the newborn screening programs because they lack sensitive and specific metabolic biomarkers, and detection of children at increased risk relies on genetic methods. Type 1 diabetes (T1D) constitutes a potential example of such disease.Between April 2018 and November 2020, over 15500 babies were enrolled into ‘INGR1D’ (Investigating Genetic Risk for T1D), a research study to identify newborns with an increased genetic risk of T1D. This project, performed as part of a T1D primary prevention study (the Primary Oral Insulin Trial, POInT), has helped to pioneer the integration of genetic screening into the NHS Newborn Blood Spot Screening Programme (NBSSP) for consenting mothers, without affecting the screening pathway. The use of prospective consent to perform personalised genetic testing on samples obtained through the routine NBSSP represents a novel mechanism for clinical genetic research in the UK and provides a model for further population based genetic studies in the newborn.This project builds on the UK’s role as a world leader in genomic medicine, e.g. through its inception and completion of the 100 000 Genomes Project, and its subsequent ambition to map 5 million further genomes over the next 5 years.Our aim is therefore to describe the methodology used by INGR1D as a way to demonstrate how a successful research and clinical trial tool can be integrated into a national screening programme, with the potential for the tool to be developed to incorporate multiple diseases with genetic markers without altering the screening pathway.
What is the effect of lockdown upon hospitalisation due to COVID-19 amongst patients from a heart failure registry?
Authors: Essa Hani , Brousas Sophia , Hupptaz Isabel Whybrow , Salmon Thomas , Sankaranarayanan Rajiv 
Published: March 2021

AbstractIntroductionCoronavirus disease 2019 (COVID-19) is associated with a high risk of mortality especially in patients with cardiovascular conditions such as heart failure. The UK government announced a national lockdown last year to curb the spread of the virus. We conducted this study primarily to ascertain the impact of lockdown upon the incidence of COVID-19 hospitalisation amongst patients with a known diagnosis of heart failure (HF)MethodsThis was a retrospective cohort study of 1097 patients from our HF registry who had presented with acute decompensated HF in 2018 and 2019. Incidence and outcomes of hospitalisation due to COVID-19 were analysed in this cohort both during the 1st UK lockdown as well as after the lockdown period. Co-morbidities, frailty index, clinical features, blood results, and heart failure treatments were compared between the 2 groups (COVID versus no-COVID) and between the group of patients who died versus survivors.Results50 out of 801 surviving (6.2%) HF patients required hospitalisation due to COVID-19 from March to November 2020; 24 patients (3.1%) during the first lockdown and 26 (3.5%) in the post-lockdown period; p=0.7. In comparison to patients not hospitalised with COVID-19 (“no-COVID group), there was a significantly higher prevalence of co-morbidities amongst HF patients who were hospitalised with COVID-19, such as hypertension (p<0.001), diabetes (p=0.005), ischaemic heart disease (p=0.01) and increased body mass index. 30 day mortality amongst HF patients hospitalised due to COVID-19 was 52%. Rockwood Frailty Score ≥6 (OR 6.530695 % CI:1.8958 to 22.4961; p=0.003) and diabetes (OR 3.82;95% CI 1.13 to 12.95; p=0.03) were independent predictors of 30 day mortality.ConclusionOur data suggests that the incidence of hospitalisation due to COVID-19 was similar both during as well as post lockdown amongst patients from our HF registry. HF patients with cardiovascular co-morbidities such as obesity, hypertension, diabetes and ischaemic heart disease have a higher risk of hospitalisation due to COVID-19. Diabetes and Rockwood Frailty score are independent predictors of short term mortality. Co-morbidity and frailty scores should be incorporated during initial assessment to help risk-prediction.
The impact of varying class sizes on epidemic spread in a university population
Authors: Best Alex , Singh Prerna , Ward Charlotte , Vitale Caterina , Oliver Megan , Idris Laminu , Poulston Alison 
Published: March 2021

AbstractA common non-pharmaceutical intervention (NPI) during the Covid-19 pandemic has been group size limits. Further, educational settings of schools and universities have either fully closed or reduced their class sizes. As countries begin to reopen classrooms, a key question will be how large classes can be while still preventing local outbreaks of disease. Here we develop and analyse a simple, stochastic epidemiological model where individuals (considered as students) live in fixed households and are assigned to a fixed class for daily lessons. We compare key measures of the epidemic - the peak infected, the total infected by day 180 and the calculatedR0- as the size of class is varied. We find that class sizes of 10 could largely restrict outbreaks and often had overlapping inter-quartile ranges with our most cautious case of classes of 5. However, class sizes of 30 or more often result in large epidemics. Reducing the class size from 40 to 10 can reduceR0by over 30%, as well as signficantly reducing the numbers infected. Intermediate class sizes show considerable variation, with the total infected varying by as much as from 10% to 80% for the same class size. We show that additional in-class NPIs can limit the epidemic still further, but that reducing class sizes appears to have a larger effect on the epidemic. We do not specifically tailor our model for Covid-19, but our results stress the importance of small class sizes for preventing large outbreaks of infectious disease.
Early medical abortion by telemedicine in the United Kingdom: A cost-effectiveness analysis
Authors: Hawkins James E , Glasier Anna , Hall Stephen , Regan Lesley ,   Homerton University Hospital Foundation Trust,   University Hospitals Bristol NHS Foundation Trust,   Aneurin Bevan University Health Board
Published: March 2021

AbstractObjectiveTo determine the potential cost savings resulting from the introduction of routine early medical abortion at home by telemedicine in the United Kingdom.DesignA cost-effectiveness analysis Setting: United KingdomPopulationWomen in 2020 undergoing early medical abortion provided by three independent abortion providers and two NHS abortion clinics.MethodsComputation of the costs of each abortion procedure and of managing failed or incomplete abortion and haemorrhage requiring blood transfusion.Outcome measuresCost savingsResultsOverall estimated cost savings are £15.80 per abortion undertaken by independent abortion providers representing a saving to the NHS of over £3 million per year. Limited data from NHS services resulted in an estimated average saving of £188.84 per abortion.ConclusionsWere telemedicine EMA to become routine, an increase in the number of women eligible for medical rather than surgical abortion, and a reduction in adverse events resulting from earlier abortion could result in significant cost-savings.Tweetable AbstractEarly medical abortion at home using telemedicine could save the NHS £3 million per year
Development of the foregut inKatharina tunicata(Mollusca; Polyplacophora)
Authors: Biggar Brandy S. 
Published: March 2021

AbstractAs a highly diverse phyla, Mollusca is both intriguing to study and difficult to define. No single common feature distinguishes the phyla, but the most common and recognizable is the radula. Throughout Molluscan history, there have been many developments to the radular structure. Evolutionary development of unique radular structures may have been made possible by developmental modularity. This histological study examines the development of polyplacophoran internal gut development. Here, I describe the developmental sequence of chiton feeding structures for the first time. Feeding structures are present by 10 days post hatch. Future research should examine larval stages prior to this in order to determine whether developmental modularity exists in polyplacophorans.
The impact of rural infrastructural investment on farmers' income growth in China
Authors: Wang Lishuang , Zhang Fan , Wang Zehao , Tan Qiu 
Published: March 2021

PurposeThe purpose of this paper is to propose and verify the influence mechanism of various kinds of infrastructure investment on farmers' income in rural China. It further analyzes the effect of rural infrastructure investment on rural economic transformation.Design/methodology/approachThis research is used to GMM model to verify the relationship between infrastructure investment and farmers' income; furthermore, the mediating effect model is used to verify the linear conduction mechanism, and panel threshold model is used to verify the nonlinear conduction mechanism.FindingsThe results show that: (1) Rural infrastructure investment can indirectly affect farmers' income by changing land efficiency and land use structure; (2) The impact of infrastructure investment on farmers' income is nonlinear; (3) Increasing infrastructural investment of productivity and transportation will contribute to accelerating the transformation of rural economy.Originality/valueThis paper expands the research on the impact of rural infrastructure investment on farmers' income; it analyzes the inner mechanism and enriches the research contents in this field; the influence of various infrastructure investment on rural economic transformation is further discussed; it provides policy suggestions and theoretical basis for accelerating the transformation of China's rural economy.
GrowBox: the reality of growth challenges for a social entrepreneur in Cape Town
Authors: Barnardo Claire , Reyneke Mignon , Ferreira Caitlin , Robertson Jeandri 
Published: March 2021

Learning outcomes
The learning outcomes of this paper is as follows: to strategically evaluate the strengths, weaknesses, threats and resulting opportunities that face an entrepreneurial startup. To apply the academic principle of competitiveness and evaluate the competitive advantage of the business and its competitors through the application of the Porter’s five forces model. To evaluate the contextual tensions that entrepreneurial ventures face, and how these affect the growth of a sustainable business. To develop the skills to create a target market analysis by using segmentation, targeting and positioning principles. To evaluate the best strategic actions to grow a business through the lens of sustainable entrepreneurship, by using principles such as the triple bottom line and people, opportunity, context and deal and framework.

Case overview/synopsis
The case look at business challenges faced by an entrepreneur, Renshia Manuel, the CEO of GrowBox, as she attempts to balance the profitability and social impact of her venture in Cape Town, South Africa. GrowBox sells customisable self-contained wooden boxes equipped with all materials to grow a variety of vegetables and herbs for consumers. Large volumes of boxes are often purchased by corporate clients who donated these to lower-income communities as part of their social responsibility projects. Additional landscaping and food-scaping services make up another revenue stream of the business. The case study documents the conception of GrowBox in 2016 and the growth of the business in the first four years of operation. The theft of equipment, and difficulty in recruiting and retaining staff due to the volatile social climate of where the business was situated, have put the business under great financial pressure and reduced the efficiency of business processes. The case highlights a number of the harsh realities of sustainable entrepreneurship where both profitability and social impact are vitally important to ensure business sustainability. The case dilemma involves the choices faced by Renshia at the beginning of 2020 regarding the future, sustainable growth of the business.

Complexity academic level
The target audience for this teaching case is primarily business students at a postgraduate level, particularly those studying in the fields of sustainable entrepreneurship and social development, as well as marketing in emerging markets. This teaching case is intended to be used as a case study in postgraduate business programmes such as postgraduate diplomas in management, specialist Masters programmes such as those focussed on entrepreneurship, social entrepreneurship or social development, as well as those studying a Master of Business Administration or related executive education programme.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 3: Entrepreneurship.
Prosecco has another story to tell: the coexistence of multiple knowledge networks in the same value chain
Authors: Sedita Silvia Rita , Hoffmann Valmir Emil , Guarnieri Patricia , Toso Carraro Ermanno 
Published: March 2021

Purpose
This paper aims to analyze how knowledge networks can be configured within a value chain and provide evidence of the coexistence of multiple knowledge networks in the same value chain.

Design/methodology/approach
The empirical setting is the Conegliano Valdobbiadene Prosecco Superiore DOCG wine cluster in the Veneto region of Northeast Italy. Data was collected through the administration by telephone of a semi-structured questionnaire to 37 oenologists, sales managers, production managers and owners of bottling companies in the district. The authors used social network analysis tools to map knowledge networks in the Prosecco cluster.

Findings
The results shed light on the importance of singling out knowledge networks in clusters at the value chain level to aid practitioners and researchers in this field. In fact, this research proves the existence of knowledge networks specificities related to the various phases of the production process.

Research limitations/implications
This study has certain limitations. The most relevant is connected to the choice to limit the analysis to a specific cluster. Future research might extend this type of analysis to multiple clusters in different locations.

Practical implications
The authors explain that in the cluster they studied, internationalization, as a common objective, might be made easier if firms could establish a more developed sales knowledge network.

Social implications
The relational approach to value chain enables disentangling specific roles of each actors. The social dimension of the value chain is taken in consideration.

Originality/value
The authors show that a firm operating in the wine industry can have different knowledge networks in the same value chain. This work adds to previous literature on knowledge networks in clusters by shedding light on an important, but still understudied aspect in the cluster functioning. Knowledge diffusion in clusters is not only uneven but is also value chain stage specific. By intersecting literature on knowledge networks, value chain and cluster research, the authors proposed a new perspective of analysis of the wine industry.