bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mRNA-LNP vaccine against Dengue Virus elicits robust, serotype-specific immunity
Authors: Wollner Clayton J. , Richner Michelle , Hassert Mariah A. , Pinto Amelia K. , Brien James D. , Richner Justin M. 
Published: January 2021

ABSTRACTDengue virus (DENV) is the most common vector-borne viral disease with nearly 400 million worldwide infections each year concentrated in the tropical and subtropical regions of the world. Severe dengue complications are often associated with a secondary heterotypic infection of one of the four circulating serotypes. In this scenario, humoral immune responses targeting cross-reactive, poorly-neutralizing epitopes can lead to increased infectivity of susceptible cells via antibody-dependent enhancement (ADE). In this way, antibodies produced in response to infection or vaccination are capable of contributing to enhanced disease in subsequent infections. Currently, there are no available therapeutics to combat DENV disease, and there is an urgent need for a safe and efficacious vaccine. Here, we developed a nucleotide-modified mRNA vaccine encoding for the membrane and envelope structural proteins from DENV serotype 1 encapsulated into lipid nanoparticles (prM/E mRNA-LNP). Vaccination of mice elicited robust antiviral immune responses comparable to viral infection with high levels of neutralizing antibody titers and antiviral CD4+and CD8+T cells. Immunocompromised AG129 mice vaccinated with the prM/E mRNA-LNP vaccine were protected from a lethal DENV challenge. Vaccination with either a wild-type vaccine, or a vaccine with mutations in the immunodominant fusion-loop epitope, elicited equivalent humoral and cell mediated immune responses. Neutralizing antibodies elicited by the vaccine were sufficient to protect against a lethal challenge. Both vaccine constructs demonstrated serotype specific immunity with minimal serum cross-reactivity and reduced ADE compared to a live DENV1 viral infection.IMPORTANCEWith 400 million worldwide infections each year, dengue is the most common vector-born viral disease. 40% of the world’s population is at risk with dengue experiencing consistent geographic spread over the years. With no therapeutics available and vaccines performing sub optimally, the need for an effective dengue vaccine is urgent. Here we develop and characterize a novel mRNA vaccine encoding for the dengue serotype 1 envelope and premembrane structural proteins that is delivered via a lipid nanoparticle. Our DENV1 prM/E mRNA-LNP vaccine induces neutralizing antibody and cellular immune responses in immunocompetent mice and protects an immunocompromised mouse from a lethal DENV challenge. Existing antibodies against dengue can enhance subsequent infections via antibody-dependent enhancement. Importantly our vaccine only induced serotype specific immune responses and did not induce ADE.
Continued need for non-pharmaceutical interventions after COVID-19 vaccination in long-term-care facilities
Authors: Love Jay , Keegan Lindsay T. , Angulo Frederick J. , McLaughlin John , Shea Kimberly M. , Swerdlow David L. , Samore Matthew H. , Toth Damon J.A. 
Published: January 2021

ABSTRACTLong-term care facilities (LTCFs) bear disproportionate burden of COVID-19 and are prioritized for vaccine deployment. LTCF outbreaks could continue occurring during vaccine rollout due to incomplete population coverage, and the effect of vaccines on viral transmission are currently unknown. Declining adherence to non-pharmaceutical interventions (NPIs) against within-facility transmission could therefore limit the effectiveness of vaccination. We built a stochastic model to simulate outbreaks in LTCF populations with differing vaccination coverage and NPI adherence to evaluate their interacting effects. Vaccination combined with strong NPI adherence produced the least morbidity and mortality. Healthcare worker vaccination improved outcomes in unvaccinated LTCF residents but was less impactful with declining NPI adherence. To prevent further illness and deaths, there is a continued need for NPIs in LTCFs during vaccine rollout.
The mechanism of full activation of tumor suppressor PTEN at the phosphoinositide-enriched membrane
Authors: Jang Hyunbum , Smith Iris Nira , Eng Charis , Nussinov Ruth 
Published: January 2021

SummaryTumor suppressor PTEN, the second most highly mutated protein in cancer, dephosphorylates signaling lipid PIP3produced by PI3Ks. Excess PIP3promotes cell proliferation. The mechanism at the membrane of this pivotal phosphatase is unknown hindering drug discovery. Exploiting explicit solvent simulations, we tracked full-length PTEN trafficking from the cytosol to the membrane. We observed its interaction with membranes composed of zwitterionic phosphatidylcholine, anionic phosphatidylserine, and phosphoinositides, including signaling lipids PIP2and PIP3. We tracked it’s moving away from the zwitterionic and getting absorbed onto anionic membrane that harbors PIP3. We followed it localizing on microdomains enriched in signaling lipids, as PI3K does, and observed PIP3allosterically unfolding the N-terminal PIP2binding domain, positioning it favorably for the polybasic motif interaction with PIP2. Finally, we determined PTEN catalytic action at the membrane, all in line with experimental observations, deciphering the mechanisms of how PTEN anchors to the membrane and restrains cancer.
Metabolite discovery through global annotation of untargeted metabolomics data
Authors: Chen Li , Lu Wenyun , Wang Lin , Xing Xi , Chen Ziyang , Teng Xin , Zeng Xianfeng , Muscarella Antonio D. , Shen Yihui , Cowan Alexis , McReynolds Melanie R. , Kennedy Brandon , Lato Ashley M. , Campagna Shawn R. , Singh Mona , Rabinowitz Joshua 
Published: January 2021

AbstractLiquid chromatography-high resolution mass spectrometry (LC-MS)-based metabolomics aims to identify and quantitate all metabolites, but most LC-MS peaks remain unidentified. Here, we present a global network optimization approach, NetID, to annotate untargeted LC-MS metabolomics data. The approach aims to generate, for all experimentally observed ion peaks, annotations that match the measured masses, retention times, and (when available) MS/MS fragmentation patterns. Peaks are connected based on mass differences reflecting adducting, fragmentation, isotopes, or feasible biochemical transformations. Global optimization generates a single network linking most observed ion peaks, enhances peak assignment accuracy, and produces chemically-informative peak-peak relationships, including for peaks lacking MS/MS spectra. Applying this approach to yeast and mouse data, we identified five novel metabolites (thiamine derivatives and N-glucosyl-taurine). Isotope tracer studies indicate active flux through these metabolites. Thus, NetID applies existing metabolomic knowledge and global optimization to annotate untargeted metabolomics data, revealing novel metabolites.
HarnessingEscherichia colifor bio-based production of formate under pressurized H2and CO2gases
Authors: Roger Magali , Reed Tom C. , Sargent Frank 
Published: January 2021

ABSRACTEscherichia coliis gram-negative bacterium that is a workhorse of the biotechnology industry. The organism has a flexible metabolism and can perform a mixed-acid fermentation under anaerobic conditions. Under these conditionsE. colisynthesises a formate hydrogenlyase isoenzyme (FHL-1) that can generate molecular hydrogen and carbon dioxide from formic acid. The reverse reaction is hydrogen-dependent carbon dioxide reduction (HDCR), which has exciting possibilities in bio-based carbon capture and storage if it can be harnessed. In this study, anE. colihost strain was optimised for the production of formate from H2and CO2during bacterial growth in a pressurised batch bioreactor. A host strain was engineered that constitutively produced the FHL-1 enzyme and incorporation of tungsten in to the enzyme, in place of molybdenum, helped poise the reaction in the HDCR direction. The engineeredE. colistrain showed an ability to grow under fermentative conditions while simultaneously producing formate from gaseous H2and CO2supplied in the bioreactor. However, while a sustained pressure of 10 bar N2had no adverse effect on cell growth, when the culture was placed at or above 4 bar pressure of a H2:CO2mixture then a clear growth deficiency was observed. Taken together, this work demonstrates that growing cells can be harnessed to hydrogenate carbon dioxide and provides fresh evidence that the FHL-1 enzyme may be intimately linked with bacterial energy metabolism.
Britain and Hong Kong: the 2019 protests and their aftermath
Authors: Summers Tim 
Published: January 2021

PurposeThe purpose of this paper is to examine British policy towards Hong Kong from the protests of 2019 through political controversies in 2020.Design/methodology/approachThe paper offers a foreign policy analysis based on a chronological account of the public interventions made by London from April 2019 to the passage of the national security law in the middle of 2020. It discusses the factors which contributed to the UK's positions and looks in more detail at an issue which relates to the British colonial legacy: the status of British National (Overseas) passport holders.FindingsThe paper argues that the UK's policy was influenced by a combination of factors: developments in Hong Kong, the implications of and perceptions about its historical position as the former colonial power, the growing influence of lobby groups in the UK and Hong Kong (especially in agenda setting), and (to a lesser extent) the UK's wider relations with China. In trying to balance these, British policy tended to be reactive rather than strategic. London generally took positions sympathetic to the protest movement and political opposition, characterised in the paper as “soft partisanship”, shifting to clear opposition to Beijing's approach when the National Security Law was announced.Social implicationsThe paper helps to understand international policy towards Hong Kong.Originality/valueThe paper offers the first account of British policy towards Hong Kong during this period and adds to the limited existing literature on the UK's Hong Kong policy over recent years. This case study sheds light on wider questions of international perceptions of developments in Hong Kong during a tumultuous period in the city's history and informs broader studies of foreign policymaking.
Environmental risk, FDI and tax reforms: why we must worry
Authors: Boachie Yiadom Eric , Mensah Lord 
Published: January 2021

PurposeIn this paper, we use empirical models to examine the main channel through which FDI escalates environmental risk. We explore whether countries with “weak” or better still low tax rate attract “dirty” FDI to deteriorate their environmentDesign/methodology/approachThe analysis uses a 40-year panel to show that foreign direct investment (FDI) and tax policy matter in accounting for cross-country environmental risk.FindingsOur sample finds support that the tax channel is the main medium through which FDI worsens environmental risk. By discomposing tax policy into low and high regimes, we report that countries that deliberately reform tax policy to bait FDI have higher environmental risk.Social implicationsA useful lesson from here is that using tax policy to lure FDI amounts to shortchanging capital risk for environmental risk.Originality/valueThe paper is unique because it identifies tax policy as a channel through which FDI affects the environment in Africa. Other studies overly simplifies the relationship between FDI and its impact on the environment, and it makes it difficult and ambiguous in offering specific policy direction.
Challenges and potential solutions to utilization of carrot rejects and waste in food processing
Authors: Kaur Gagan Jyot , Orsat Valerie , Singh Ashutosh 
Published: January 2021

PurposeOf the global carrot production, 20–30% is outgraded as carrot rejects and waste (CRW) at the primary processing level, which is partially used toward animal feed and the remaining ends in the landfills. This study was undertaken to identify the hurdles and seek potential solutions for using CRW in food processing.Design/methodology/approachCRW were procured from the processing unit in Ontario, Canada, as (1) outgraded carrots (OGCs) and (2) processed discards (PDs). The physical parameters of CRW, imperfections responsible for their separation from the graded carrots and shelf-life studies were recorded.FindingsA significant difference with p ≤ 0.05 was recorded for both the physical parameters and the nature of imperfections in CRW. Discolored carrots (42.37 ± 3.59%) and the presence of vertical splits (52.71 ± 3.18%) were among the top defects in the OGCs. In contrast, the presence of broken tips (54.83 ± 2.52%) and vertical splits (40.56 ± 2.65%) were among the primary cause for the generation of PDs. In total, five percent of CRW were initially infected, which later increased to 30% during the seven days storage period.Research limitations/implicationsThe limitation of the study was that only two varieties of carrots were considered and these were procured from one processor (the authors’ industry partner) at different time intervals of the year. Microbiological analysis could not be completed and reported due to prevailing coronavirus disease 2019 (COVID-19) situation but is included for future studies.Practical implicationsDevelopment of specialized post-harvest packaging and handling protocols and separation of infected fragments are essential before suggesting the use of CRW in food processing.Originality/valueNumerous studies report on the post-harvest management and processing of graded carrots, but limited to no studies are published on the usage of CRW in food processing.
Development and application of a service design-based process for improvement of human resource management service quality
Authors: Mashhady Arash , Khalili Hamidreza , Sameti Ardalan 
Published: January 2021

PurposeThis research approaches human resource management (HRM) as a service and aims to develop and test a process for improving perceived HRM service quality.Design/methodology/approachA three-step process was developed by incorporating concepts and tools from service design approach. Based on the literature, it was hypothesized that applying this process could improve perception of HRM service quality, perceived HRM service value, level of leader–member exchanges along with perceived organizational support, role clarity and role ambiguity. A case study was conducted and these variables were measured and compared, before and after testing the process for a test group and a control group within an organization.FindingsThe main findings suggest the effectiveness of the presented process in improving the perceived HRM service quality and social exchanges (in terms of perceived organizational support and leader–member exchanges), while reducing role conflict and role ambiguity in employees and supervisors.Practical implicationsIn a general sense, the obtained result implies that leveraging holistic and collaborative service design tools and concepts in (re)designing internal services, such as HRM, could improve perception of quality in organizational services, which in turn may lead to several important benefits for organizations, particularly in terms of HRM as per the context of this study.Originality/valueThis paper demonstrates development of an employee-centered method by borrowing from service design concepts and tools, to improve the perception of HRM service quality.
An examination of the effects of cross-docking on retail out of stock
Authors: Benrqya Yassine 
Published: January 2021

PurposeThe objective of this paper is to examine the impact of cross-docking on the retail out of stock (OOS).Design/methodology/approachThe research is based on a three-phase Delphi study consisting of a seeding/literature review phase, a pre-testing phase and a three-round Delphi study. The Delphi study used in this paper brings together leading supply chain management experts with leading academics.FindingsThe findings of the paper show that cross-docking may impact the retailers OOS drivers positively or negatively. The study demonstrates that cross-docking has a negative impact on ordering, placement, delivery, handling, DC handling and receipt. On the other hand, cross-docking has a positive effect on supplier ordering. Finally, academics and supply chain managers disagreed on the effect of cross-docking on the promotions driver. Academics consider that cross-docking has a positive impact on promotions OOS driver, while supply chain managers believe the opposite.Research limitations/implicationsThe Delphi study was administrated to supply chain managers from a single major FMCG company, which is a supplier of grocery retailers. By including supply chain managers from the retailers' side, more perspectives on the impact of cross-docking on the OOS drivers can be investigated.Originality/valueThe study develops an original instrument to investigate the impact of cross-docking on OOS drivers. This is the first scholarly work to investigate the relationship between a distribution strategy and the OOS drivers.
Assessing the economic viability of commercial moringa production for Kenyan small-scale farmers
Authors: Waterman Carrie , Peterson Austin , Schelle Celina , Vosti Steven A. , McMullin Stepha 
Published: January 2021

PurposeMoringa (Moringa oleifera) is a highly nutritious, fast-growing crop that has emerged in Western markets as a “superfood” and as a “smart crop” for income generation potential among small-scale farmers. As such, moringa has been widely promoted by agricultural development practitioners in low-income countries and by emerging businesses aimed at achieving nutritional and social impact. However, the intrinsic nutritional and agronomic strengths of moringa are not enough to warrant its widespread promotion without first evaluating its economic potential to farmers.Design/methodology/approachA Land Use System (LUS) analysis modeling tool was employed to test the economic performance of two sets of moringa production practices in Kenya. Data were collected during in-depth interviews and field visits with farmers in Meru that supply a local market, and in Shimba Hills that supply an organic export market.FindingsResults suggest that current production practices over an 12-years assessment period generate a Net Present Value (NPV) of US$8,049 [ha-1] in Meru and a negative NPV of US$697 [ha-1] in Shimba Hills; with average daily returns to family labor of these two production systems of roughly 1.6 times and 0.13 times the prevailing local wage rate, respectively. These differences were attributed to a higher farmgate prices and greater yields in Meru. The analysis tool was then used to predict the effects of changes in farming practices, e.g. if farmers in Meru switched to intensive bed cultivation NPV is estimated to increase by ∼650%.Research limitations/implicationsThis study demonstrates the importance of examining the economic performance of agricultural production systems intended to increase the benefits to small-scale farmers.Originality/valueOur study is the first to assess moringa's economic performance within two production systems in Kenya – a local farmers' cooperative in Meru, and a group of farmers contracted by an export company.
Corporate social responsibility and dividend policy: a strategic choice in family firms
Authors: Sheikh Muhammad Fayyaz , Bhutta Aamir Inam , Rehman Bareera , Bazil Muhammad , Hassan Ali 
Published: January 2021

PurposeThe purpose of this study is to examine whether corporate social responsibility (CSR) affects dividend policy (the propensity to pay dividends as well as the dividend payout ratio) and what role family ownership plays in this regard in an emerging market.Design/methodology/approachThe study uses a sample of 1,480 observations from Pakistan for the period 2010–2016 and accounts for Hackman self-selection bias and endogeneity issues using a robust regression analysis. CSR activity is measured by CSR score developed through a content analysis of firms' annual reports.FindingsThe study finds that the greater number of CSR activities increases the propensity to pay dividends, but reduces the dividend payout in dividend-paying firms. On the other hand, in family firms, the greater number CSR activities decreases the propensity to pay dividends, but increases the dividend payout in dividend-paying firms. The findings hold for a series of robustness and sensitivity checks, for example, alternative measures, specifications and estimators.Practical implicationsA trade-off between firms' CSR activities and dividend policy needs to be the point of concern for investors, minority shareholders and policy makers. The role of the non-executive and independent directors becomes more important, especially in the family firms where family members sitting on the boards may drive CSR activities in their own interests opportunistically. The potential opportunistic behaviour of family members warrants the need for policy reform initiatives to strengthen the protection of other stakeholders' interests.Originality/valueThe study highlights that family owners' efforts to preserve their socio-emotional wealth in family firms affect the relationship between CSR activities and dividend policy. Further, the relationship between CSR and dividend policy in emerging markets is different from developed markets. This study simultaneously focuses on both the propensity to pay dividends and the amount of dividend payment and documents that the implications of CSR are different for them.
The effect of payment method and multimorbidity on health and healthcare utilisation
Authors: Hayes Helen , Stokes Jonathan , Kristensen Søren Rud , Sutton Matt 
Published: January 2021

PurposeThree types of payment methods have been introduced across European countries in attempts to encourage better, more integrated care of persons with multimorbidity: pay-for-performance; pay-for-coordination; and an all-inclusive payment method. We examine whether there are differences in the way these payment methods affect health and healthcare use in persons with multimorbidity.Design/methodology/approachUsing individual-level survey data from twenty European countries, we examine unadjusted differences in average outcomes for the years 2011–2015 by whether countries adopted new payment methods for integrated care. We then test for a differential effect for multimorbid persons using linear, individual random effects regressions, including country and time fixed effects and clustering standard errors at the country level.FindingsWe find little effect of varying payment methods on key outcomes for multimorbid individuals despite the theoretical predictions and the rhetoric in many policy documents.Research limitations/implicationsPolicymakers should bear in mind that the success of the payment method relies on the specific design of the incentives and their implementation. New effective models of care and how to incentivise these for multimorbid patients is an ongoing research priority.Originality/valueThis paper is the first to study the effects of payments for integration on the dimensions and populations these schemes intend to affect; health and healthcare use at the individual level for multimorbid individuals.