bluuebunny/crossref_metadata_2025_split huggingface dataset:
The beryllium fluoride form of the Na+,K+-ATPase and the intermediates of the functional cycle
Authors: Fruergaard Marlene U. , Dach Ingrid , Andersen Jacob L. , Ozol Mette , Shasavar Azadeh , Quistgaard Esben M. , Poulsen Hanne , Fedosova Natalya U. , Nissen Poul 
Published: November 2021

AbstractThe Na+,K+-ATPase generates electrochemical gradients of Na+ and K+ across the plasma membrane. Here, we describe a 4.0 Å resolution crystal structure of the pig kidney Na+,K+-ATPase stabilized by beryllium fluoride (denoted E2-BeFx). The structure shows high resemblance to the E2P phosphoenzyme obtained by phosphorylation from inorganic phosphate (Pi) and stabilised by cardiotonic steroids, and reveals a Mg2+ bound near the ion binding site II. Anomalous Fourier analysis of the crystals soaked in Rb+ (K+ congener) followed by a low resolution rigid-body refinement (6.9-7.5 Å) revealed pre-occlusion transitions leading to activation of the desphosphorylation reaction. Mg2+ location indicates a site of an initial K+ recognition and acceptance upon binding to the outward-open E2P state after Na+ release. Despite the overall structural resemblance to the Pi-induced E2P phosphoform, BeFx inhibited enzyme is able to bind both ADP/ATP and ions - features that relate E2-BeFx complex to an intermediate of the functional cycle of the Na+,K+-ATPase prior E2P.
ChAdOx1 n-COV-19 Vaccine Side Effects Among Health Care Workers in Trinidad and Tobago
Authors: Gopaul Chavin D. , Ventour Dale , Thomas Davlin 
Published: November 2021

AbstractBackgroundThe pharmaceutical firms have been lauded for the swift development, trial, approval, and rollout of various Covid-19 vaccines. However, a key issue in the vaccination campaign relates to vaccine hesitancy due to concerns on Covid-19 vaccines safety.MethodA retrospective longitudinal study was carried out via a telephone validated questionnaire. The questionnaire domains included demographic data, medical and COVID-19 related anamneses, and local and systemic side effects 48 hours after receiving the first dose of the vaccine and 48 hours after receiving the second dose of the vaccine.ResultsThe questionnaire was administered to a sample of 687 healthcare workers (Male = 275; Female = 412). The results indicated that the incidence of reported fever, body pain, chills, nausea, myalgia, headache, malaise, fatigue and other systemic symptoms declined significantly 48 hours after administration of the second dose compared to the first dose. The Chi-square test and multiple logistics regression results were consistent in demonstrating that younger vaccine recipients were more likely to report fever, body pain, chills, nausea, myalgia, headache, fatigue and other symptoms compared to older vaccine recipients. The multiple logistics regression indicate that female vaccine recipients had greater odds of reporting headache, fatigue, discomfort and less likely to report no symptoms compared to male vaccine recipients, 48 hours after receiving both doses.ConclusionsThe findings indicate that on average, vaccine recipients reported fewer number of local and systemic side effects within 48 hours after receiving the second dose compared to 48 hours after receiving the first dose. The findings have implications on public health policy efforts to lower vaccine hesitancy.
Viral kinetic modeling and clinical trial simulation predicts disruption of respiratory disease trials by non-pharmaceutical COVID-19 interventions
Authors: Arsène Simon , Couty Claire , Faddeenkov Igor , Go Natacha , Granjeon-Noriot Solène , Šmít Daniel , Kahoul Riad , Illigens Ben , Boissel Jean-Pierre , Chevalier Aude , Lehr Lorenz , Pasquali Christian , Kulesza Alexander 
Published: November 2021

ABSTRACTClinical research in infectious respiratory diseases has been profoundly affected by non-pharmaceutical interventions (NPIs) against COVID-19. On top of trial delays or even discontinuation which have been observed in all disease areas, NPIs altered transmission pattern of many seasonal respiratory viruses which followed regular patterns for decades before the pandemic. Clinical trial design based on pre-pandemic historical data therefore needs to be put in question. In this article, we show how knowledge-based mathematical modeling can be used to address this issue. We set up an epidemiological model of respiratory tract infection (RTI) sensitive to a time dependent between-host transmission rate and coupled this model to a mechanistic description of viral RTI episodes in an individual patient. By reducing the transmission rate when the lockdown was introduced in the United Kingdom in March 2020, we were able to reproduce the perturbed 2020 RTI disease burden data. Using this setup, we simulated several NPIs scenarios of various strength (none, mild, medium, strong) and conducted placebo-controlled in silico clinical trials in pediatric patients with recurrent RTIs (RRTI) quantifying annual RTI rate distributions. In interventional arms, virtual patients aged 1-5 years received the bacterial lysate OM-85 (approved in several countries for the prevention of pediatric RRTIs) through a pro-type I immunomodulation mechanism of action described by a physiologically based pharmacokinetics and pharmacodynamics approach (PBPK/PD). Our predictions showed that sample size estimates based on the ratio of RTI rates (or the post-hoc power of fixed sample size trials) are not majorly impacted under NPIs which are less severe (none, mild and medium NPIs) than a strict lockdown (strong NPI). However, NPIs show a stronger impact on metrics more relevant for assessing the clinical relevance of the effect such as absolute benefit. This dichotomy shows the risk that successful trials (even with their primary endpoints being met) still get challenged in risk benefit assessment during the review of market authorization. Furthermore, we found that a mild NPI scenario already affected the time to recruit significantly when sticking to eligibility criteria complying with historical data. In summary, our model predictions can help rationalize and forecast post-COVID-19 trial feasibility. They advocate for gauging absolute and relative benefit metrics as well as clinical relevance for assessing efficacy hypotheses in trial design and they question eligibility criteria misaligned with the actual disease burden.
The P681H mutation in the Spike glycoprotein confers Type I interferon resistance in the SARS-CoV-2 alpha (B.1.1.7) variant
Authors: Lista Maria Jose , Winstone Helena , Wilson Harry D , Dyer Adam , Pickering Suzanne , Galao Rui Pedro , De Lorenzo Giuditta , Cowton Vanessa M. , Furnon Wilhelm , Suarez Nicolas , Orton Richard , Palmarini Massimo , Patel Arvind H. , Snell Luke , Nebbia Gaia , Swanson Chad , Neil Stuart J D 
Published: November 2021

SUMMARYVariants of concern (VOCs) of severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) threaten the global response to the COVID-19 pandemic. The alpha (B.1.1.7) variant appeared in the UK became dominant in Europe and North America in early 2021. The Spike glycoprotein of alpha has acquired a number mutations including the P681H mutation in the polybasic cleavage site that has been suggested to enhance Spike cleavage. Here, we show that the alpha Spike protein confers a level of resistance to the effects of interferon-β (IFNβ) in lung epithelial cells. This correlates with resistance to restriction mediated by interferon-induced transmembrane protein-2 (IFITM2) and a pronounced infection enhancement by IFITM3. Furthermore, the P681H mutation is necessary for comparative resistance to IFNβ in a molecularly cloned SARS-CoV-2 encoding alpha Spike. Overall, we suggest that in addition to adaptive immune escape, mutations associated with VOCs also confer replication advantage through adaptation to resist innate immunity.
Host-associated phages disperse across the extraterrestrial analogue Antarctica
Authors: Rahlff Janina , Bornemann Till L.V. , Lopatina Anna , Severinov Konstantin , Probst Alexander J. 
Published: November 2021

AbstractExtreme Antarctic conditions provide one of the closest analogues of extraterrestrial environments. Since air and snow samples, especially from polar regions, yield DNA amounts in the lower picogram range, binning of prokaryotic genomes is challenging and renders studying the dispersal of biological entities across these environments difficult. Here, we hypothesized that dispersal of host-associated bacteriophages (adsorbed, replicating or prophages) across the Antarctic continent can be tracked via their genetic signatures aiding our understanding of virus and host dispersal across long distances. Phage genome fragments (PGFs) reconstructed from surface snow metagenomes of three Antarctic stations were assigned to four host genomes, mainly Betaproteobacteria includingRalstoniaspp. We reconstructed the complete genome of a temperate phage with near-complete alignment to a prophage in the reference genome ofRalstonia pickettii12D. PGFs from different stations were related to each other at the genus level and matched similar hosts. Metagenomic read mapping and nucleotide polymorphism analysis revealed a wide dispersal of highly identical PGFs, 13 of which were detected in seawater from the Western Antarctic Peninsula in distance of 5538 km to the snow sampling stations. Our results suggest that host-associated phages, especially ofRalstoniasp., disperse over long distances despite harsh conditions of the Antarctic continent. Given that 14 phages associated with twoR. pickettiidraft genomes isolated from space equipment were identified, we conclude thatRalstoniaphages are ideal mobile genetic elements to track dispersal and contamination in ecosystems relevant for Astrobiology.ImportanceHost-associated phages of the bacteriumRalstoniaidentified in snow samples can be used to track microbial dispersal over thousands of kilometers across the Antarctic continent, which functions as an extraterrestrial analogue because of its harsh environmental conditions. Due to presence of these bacteria carrying genome-integrated prophages on space-related equipment, and the here demonstrated potential for dispersal of host-associated phages, our work has implications for Planetary Protection, a discipline in Astrobiology interested in preventing contamination of celestial bodies with alien biomolecules or forms of life.
Bringing innovation back in–strategies and driving forces behind entrepreneurial responses in small-scale rural industries in Sweden
Authors: Rytkönen Paulina Ines , Oghazi Pejvak 
Published: November 2021

PurposeThe paper contributes to the debate about local food and conceptualization of rural entrepreneurship by analysing the performance of small-scale dairies departing from their relation to innovations, innovative activities and risk.Design/methodology/approachThe authors use phenomenography to identify representative categories, and to draw conclusions about how these are consistent or different from dominant definitions of rural entrepreneurship and self-employment. The authors conducted semi-structured interviews, participatory workshops and compiled a database of all small-scale dairies established between 1968 and 2020.FindingsA focus on innovations contributes to differentiate between rural entrepreneurship and self-employment and how these interact in the process of economic growth. Innovations are seldom disruptive. Instead, innovative behaviour is strongly related to business models and to imitation. Social capital and collective action play a key role for the innovative capacity of small businesses, especially to realize disruptive innovations, such as the establishment of a new market.Research limitations/implicationsThe innovative capacity of rural businesses can be understood through their ability to break patterns, alter institutions and turn embededdness into assets. Rural entrepreneurship and self-employment are intertwined in the economic growth process.Practical implicationsInnovative behaviour is a significant aspect for firm survival over time, and it is also strongly related to new business models. Most rural firms can be characterized as self-employment, the latter are essential because they provide rural livelihoods and help bring maturity to newly established markets.Social implicationsThe right type of support, e.g. adopting enabling industrial regulations and granting access to constructive experiences of others, contributes to the innovative behaviour of small-scale rural firms.Originality/valueThis study differentiates rural entrepreneurship from rural self-employment by analysing the role of innovation. The authors show how innovations and innovative behaviour work their way through the process of economic growth and how innovation can break patterns by turning rural embeddedness into assets; and how innovative behaviour related to self-employments contributes to the creation of value and interacts with entrepreneurship in the process of economic growth.
Social media's impact on the empowerment of women and youth male entrepreneurs in Egypt
Authors: Miniesy Rania , Elshahawy Engy , Fakhreldin Hadia 
Published: November 2021

PurposeThis study aims to examine the impact of social media (SM) on the creation of digital entrepreneurship by female (irrespective of age) and youth male (aged 18–29 years) entrepreneurs, investigate if SM empowers those entrepreneurs and compare the empowerment characteristics between female and youth male entrepreneurs before and after starting their businesses.Design/methodology/approachSelf-assessment questionnaires were collected from a sample of 408 Egyptian female and youth male digital entrepreneurs from Greater Cairo, whose businesses had been operating for more than one year.FindingsThe research showed the following four results: Of the surveyed entrepreneurs, 95% asserted that without SM, they would not have started their businesses. Female and youth male entrepreneurs are empowered both on personal and relational levels, and women’s empowerment is more evident in the latter. Before digital entrepreneurship, youth males have significantly higher averages than female entrepreneurs in almost all empowerment characteristics, whereas after digital entrepreneurship, female entrepreneurs have significantly higher averages in making decisions related to investment, personal education and personal health, as well as those of other household members. Female entrepreneurs are relatively more empowered than youth males after digital entrepreneurship when each group is compared with its initial status.Originality/valueThis study’s originality stems from using a large sample of entrepreneurs, including youth males, not just females; employing a more structured, comprehensive measure of empowerment than found in the literature because it included the rarely used psychological dimension; considering more than one SM tool and comparing empowerment of females to that of youth males.
Would compensation be necessary? The importance of service recovery strategy in e-retail delivery problems
Authors: Yunus Erlinda Nusron 
Published: November 2021

PurposeThis study examines the different effects of service recovery strategies on customers' future intentions when online shoppers were experiencing delivery failures. Two types of problem severity are evaluated: wrong-product delivery (issues with the product quality or quantity) and late delivery. This study also investigates the impact of service criticality on the relationship between service recovery strategies and customers' future intentions.Design/methodology/approachThis study employs experimental research with 123 online shoppers as participants. Following the results, a subsequent test is conducted to examine the effect of participants' demographics on future intentions. Finally, the current study elaborates the findings using qualitative research, interviewing both sides impacted by the service failures: online shoppers and e-retail managers.FindingsThe findings show that complementing product replacement with monetary compensation is the most effective strategy to improve repurchase intention after a dissatisfaction moment. This effect is indifferent to service criticality and severity. Age influences the participants' repurchase intentions, in which younger people are less tolerant of service failures. In contrast, gender and education level do not provide any differences. To prevent delivery failures, managers participating in this study suggest several best practices regarding systems and infrastructure, people and coordination and collaboration with logistics partners.Research limitations/implicationsThe study mainly examines a limited type of service and service failures. Further studies are encouraged to expand the variables and scenarios, as well as to employ more distinctive methods, to enrich the findings related to recovery strategy in the e-commerce industry.Practical implicationsGiven proper compensation, service failure could create momentum for online retailers to boost customer loyalty. This study suggests that managers design the most effective service recovery to win customers back to the business.Originality/valueThis paper enriches the literature related to a service recovery strategy, particularly within the online shopping context.
The global economic cost of coronavirus pandemic: current and future implications
Authors: Ajmal Mian M. , Khan Mehmood , Shad Muhammad Kashif 
Published: November 2021

PurposeThe global economy is plagued by an unprecedented shock that has devastated economic growth under the coronavirus pandemic. The prolonged movement control orders, social distancing, and lockdowns have triggered the global economic downturn, disrupted the demand and supply chains, reduced the pool of workforce, and caused many jobs loss. This paper aims to analyze the global economic cost of the coronavirus pandemic, and its current and future implications.Design/methodology/approachBased on contingency theory, this paper provides an in-depth analysis of the current situation on the global economic cost of the COVID-19 outbreak and gives insights from an organizational perspective.FindingsThis paper found that the world has witnessed far-ranging economic consequences due to the coronavirus pandemic in four aspects: (i) decline in personal consumption; (ii) decline in the investments and stock prices in capital market; (iii) decline in government spending in developmental projects and increase in new borrowing; and (iv) decline of exports of goods to international markets.Originality/valueThe novelty lies in investigating the effects of the COVID-19 pandemic on micro and macroeconomic levels — the components of GDP, consumer behavior, business investments, government spending, and global exports. The paper suggests the need for urgent actions by the world leaders to oversee, anticipate, and manage the risks and cushion the economic consequences. It concludes that the flexibility and adaptability of leaders, effectiveness, workforce protection, efficient use of modern technology, including automation and artificial intelligence, would enhance the resilience of supply chains which will support organizations to sustain in this critical time.
Is steroid pulse therapy a suitable treatment for drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms? A systematic review of case reports in patients treated with corticosteroids in Japan
Authors: Hashizume Hideo , Ishikawa Yuto , Ajima Sayaka 
Published: November 2021

AbstractDrug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms is a life‐threatening severe cutaneous adverse reaction, characterized by multiple organ involvement and reactivation of herpes viruses. Although the mainstay of treatment is a high dosage of corticosteroids delivered by pulse therapy or conventional oral administration, it remains debatable which mode is better. To clarify this issue, we reviewed publications in Japan of 299 cases of drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms treated with corticosteroids, to evaluate safety concerns with regards to these two modes of treatment. As a result, we found that patients treated with pulse therapy more frequently suffered cytomegalovirus reactivation, persistency, and high mortality but less frequently experienced herpesvirus 6 reactivation or type 1 diabetes compared with those undergoing conventional treatment, suggesting that the administration mode may differentially modulate inflammatory responses toward distinct consequences. This is the first statistical analysis revealing that steroid pulse therapy frequently resulted in severe sequelae with high mortality. In terms of the risk of serious consequences, we consider that steroid pulse therapy should be eschewed for the treatment of drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms.
Host–parasite dynamics shaped by temperature and genotype: Quantifying the role of underlying vital rates
Authors: Bruijning Marjolein , Fossen Erlend I. F. , Jongejans Eelke , Vanvelk Héléne , Raeymaekers Joost A. M. , Govaert Lynn , Brans Kristien I. , Einum Sigurd , De Meester Luc 
Published: November 2021

Abstract

Global warming challenges the persistence of local populations, not only through heat‐induced stress, but also through indirect biotic changes. We study the interactive effects of temperature, competition and parasitism in the water flea Daphnia magna.

We carried out a common garden experiment monitoring the dynamics of Daphnia populations along a temperature gradient. Halfway through the experiment, all populations became infected with the ectoparasite Amoebidium parasiticum, enabling us to study the interactive effects of temperature and parasite dynamics. We combined Integral Projection Models with epidemiological models, parameterized using the experimental data on the performance of individuals within dynamic populations. This enabled us to quantify the contribution of different vital rates and epidemiological parameters to population fitness across temperatures and Daphnia clones originating from two latitudes.

Interactions between temperature and parasitism shaped competition, where Belgian clones performed better under infection than Norwegian clones. Infected Daphnia populations performed better at higher than at lower temperatures, mainly due to an increased host capability of reducing parasite loads. Temperature strongly affected individual vital rates, but effects largely cancelled out on a population‐level. In contrast, parasitism strongly reduced fitness through consistent negative effects on all vital rates. As a result, temperature‐mediated parasitism was more important than the direct effects of temperature in shaping population dynamics. Both the outcome of the competition treatments and the observed extinction patterns support our modelling results.

Our study highlights that shifts in biotic interactions can be equally or more important for responses to warming than direct physiological effects of warming, emphasizing that we need to include such interactions in our studies to predict the competitive ability of natural populations experiencing global warming.

A free Plain Language Summary can be found within the Supporting Information of this article.