bluuebunny/crossref_metadata_2025 huggingface dataset:
drda: An R package for dose-response data analysis
Authors: Malyutina Alina , Tang Jing , Pessia Alberto
Published: June 2021

Analysis of dose-response data is an important step in many scientific disciplines, including but not limited to pharmacology, toxicology, and epidemiology. The R package drda is designed to facilitate the analysis of dose-response data by implementing efficient and accurate functions with a familiar interface. With drda, it is possible to fit models by the method of least squares, perform goodness of fit tests, and conduct model selection. Compared to other similar packages, drda provides, in general, more accurate estimates in the least-squares sense. This result is achieved by a smart choice of the starting point in the optimization algorithm and by implementing the Newton method with a trust region with analytical gradients and Hessian matrices. In this article, drda is presented through the description of its methodological components and examples of its user-friendly functions. Performance is finally evaluated using a real, large-scale drug sensitivity screening dataset.
Sequence of the SARS-CoV-2 spike transmembrane domain makes it inherently dynamic
Authors: Lall Sahil , Balaram Padmanabhan , Mathew M.K. , Gosavi Shachi
Published: June 2021

The homotrimeric SARS-CoV-2 spike protein enables viral infection by mediating the fusion of the viral envelope with the host membrane. The spike protein is anchored to the SARS-CoV-2 envelope by its transmembrane domain (TMD), which is composed of three TM helices, each contributed by one of the protomers of the homotrimeric spike. Although the TMD is important for SARS-CoV-2 viral fusion and is well-conserved across the Coronaviridae family, it is unclear whether it is a passive anchor of the spike or actively promotes viral fusion. Specifically, the nature of the TMD dynamics and how these dynamics couple to the large pre- to post-fusion conformational transition of the spike ectomembrane domains remains unknown. Here, we computationally study the SARS-CoV-2 spike TMD in both homogenous POPC and cholesterol containing membranes to characterize its structure, dynamics, and self-assembly. Different tools identify distinct segments of the spike sequence as its TM helix. Atomistic simulations of a spike protomer segment that includes the superset of the TM helix predictions show that the membrane-embedded TM sequence bobs, tilts and gains and loses helicity at the membrane edges. Coarse-grained multimerization simulations using representative TM helix structures from the atomistic simulations exhibit diverse trimer populations whose architecture depends on the structure of the TM helix protomer. Multiple overlapping and conflicting dimerization interfaces stabilized these trimeric populations. An asymmetric conformation is populated in addition to a symmetric conformation and several in-between trimeric conformations. While the symmetric conformation reflects the symmetry of the resting spike, the asymmetric TMD conformation could promote viral membrane fusion through the stabilization of a fusion intermediate. Together, our simulations demonstrate that the SARS-CoV-2 spike TM anchor sequence is inherently dynamic, trimerization does not abrogate these dynamics and the various observed TMD conformations may enable viral fusion.
Insulin signaling couples growth and early maturation to cholesterol intake
Authors: Texada Michael J. , Lassen Mette , Pedersen Lisa H. , Malita Alina , Rewitz Kim
Published: June 2021

Nutrition is one of the most important influences on growth and the timing of developmental maturation transitions including mammalian puberty and insect metamorphosis. Childhood obesity is associated with precocious puberty, but the assessment mechanism that links body fat to early maturation is unknown. During development, intake of nutrients promotes signaling through insulin-like systems that govern the growth of cells and tissues and also regulates the timely production of the steroid hormones that initiate the juvenile-adult transition. We show here that the dietary lipid cholesterol, required as a component of cell membranes and as a substrate for steroid biosynthesis, also governs body growth and maturation in Drosophila via promoting the expression and release of insulin-like peptides. This nutritional input acts via the Niemann-Pick-type-C (Npc) cholesterol sensors/transporters in the glia of the blood-brain barrier and cells of the adipose tissue to remotely drive systemic insulin signaling and body growth. Furthermore, increasing intracellular cholesterol levels in the steroid-producing prothoracic gland strongly promotes endoreduplication, leading to accelerated attainment of a nutritional checkpoint that ensures that animals do not initiate maturation prematurely. These findings couple sensing of the lipid cholesterol to growth control and maturational timing, which may help explain both the link between cholesterol and cancer as well as the critical connection between body fat (obesity) and early puberty.

HIGHLIGHTS

Dietary cholesterol promotes developmental growth and leads to early maturation

Insulin signaling couples cholesterol intake with systemic growth

Cholesterol promotes insulin signaling and growth via glial and fat-tissue relays

Cholesterol sensing affects a nutritional checkpoint that prevents early maturation

GRAPHICAL ABSTRACT
Education as a key to provide the growth of entrepreneurial intentions
Authors: Pinto Borges Ana , Lopes João M. , Carvalho Catarina , Vieira Bruno Miguel , Lopes Jorge
Published: June 2021

Purpose

The purpose of this study is to analyze the entrepreneurial intentions of higher education students in a private higher education institution (HEI), enrolled in the following courses: Business Management, Hospitality Management, Tourism and Business Relations.

Design/methodology/approach

A quantitative methodology was used through the application of a questionnaire in a private HEI located in the northern region of Portugal and 228 valid responses were collected.

Findings

We have found out that (1) the elder the students are, the higher is the probability that they will consider entrepreneurship as the first option to enter the job market; (2) the courses of Business Management and Hotel Management are those that influence the entrepreneurial intentions most positively; (3) the more prepared a student feels in order to start a business, the more likely he will become an entrepreneur; (4) to consider entrepreneurship as the first option to enter the job market is positively influenced by the dimensions of the Attitude Toward Enterprise (ATE), namely, leadership, creativity, achievement and personal control; (5) to have a business idea could be motivated by the course in which the students are enrolled in, if they feel they are prepared to start a business, and by the dimensions of ATE.

Practical implications

HEIs and/or regional governments may have an entrepreneurship support office, where students can get assistance in the process of creating their companies and develop innovative entrepreneurial models adapted to older students. The creation of “senior entrepreneurial ecosystems” can be an interesting path to be explored. HEIs can make extracurricular activities available to students. Policymakers must introduce entrepreneurship to primary and secondary education.

Originality/value

This study increases the understanding of the individual characteristics of the students in a private HEI, as well as the courses that positively influence entrepreneurial intentions.
Cash waqf risk management and perpetuity restriction conundrum
Authors: Azrai Azaimi Ambrose Azniza Hartini , Abdullah Asuhaimi Fadhilah
Published: June 2021

Purpose

The purpose of this paper is to comprehensively discuss the issue of risk vis-à-vis the perpetuity restriction principle inherent in waqf (Islamic endowment). Specifically, it attempts to consolidate the axioms in both conventional and Islamic finance, such as the risk-return trade-off and al-ghunm bi al-ghurm (liability accompanies gain), with the perpetual nature of waqf. Overall, this paper attempts to find a resolution to the dilemma of perpetuity restriction inherent in cash waqf against the natural occurrence of the risk.

Design/methodology/approach

This paper is based on the secondary research methodology; past literature encompassing journal articles, books, relevant financial axioms, fatwas (Islamic rulings) and state enactments is critically reviewed to present its case. In regard to state enactments, only Malaysian state enactments have been used, thus restricting the study to the Malaysian case only.

Findings

This study contends that the dilemma of the perpetuity restriction and the natural occurrence of risk can be resolved through the integration of waqf risk management, especially concerning cash waqf, with the Islamic spiritual approach. By implementing standard operating procedures that inculcate awareness on waqf risk management and Islamic spirituality in waqf stakeholders (wāqif (donor), trustee and beneficiaries), the stakeholders may accept the reality of risk that is inevitable even after all efforts have been exhausted. In other words, the violation of perpetuity is exonerated given that mental faculties aligned with revealed texts have been exhaustively used beforehand.

Practical implications

Findings from this study may broaden the choice of investment avenues for waqf trustees while adhering to the perpetual restriction of waqf. More importantly, waqf trustees will not be forced to invest in interest-bearing securities or be involved in any usurious transactions just to obtain guaranteed returns and preserve the corpus of waqf.

Originality/value

This study offers a unique perspective on cash waqf risk management by re-analyzing the axioms and concepts of finance and waqf while observing the welfare of the beneficiaries.
A foundational framework for agile enterprise architecture
Authors: Kaddoumi Tarek , Watfa Mohamed
Published: June 2021

Purpose

The application of agility principles and methodologies on Enterprise Architecture (EA) is a promising field. This paper aims to provide an in-depth study of the Agile Enterprise Architecture (AEA) by studying EA practitioners’ perspectives to propose a foundational framework for AEA.

Design/methodology/approach

The authors formulate a foundational framework that defines the AEA motivators, enablers and blockers using the agile manifesto as one of the AEA enablers where a total of 156 EA stakeholders with at least one year of experience in enterprise architecture were surveyed, and a set of hypotheses was analyzed and tested based on the proposed framework. The authors also develop a quantitative method to evaluate the agility index of the EA based on the introduced framework.

Findings

The research results show with significance that enterprise architects perceive positively the application of the agility methodologies on the enterprise architecture. This perception is primarily affected by the enterprise size, the EA dependency and the agile methodologies awareness. The findings also indicate that AEA is primarily motivated by the Business and IT Change Ready and Responsive EA. Finally, an EA Agility Index (EAAI) was designed to assess the agility application of the EA based on the three forces, i.e. motivators, enablers and blockers.

Research limitations/implications

Because of the chosen research approach and the sample size, the research results may lack generalizability. Also, EAAI designed was not thoroughly tested.

Practical implications

The paper includes implications for the design and development of an EA Agility Index, and the need to increase the awareness of the agility methodologies to overcome the blocker of the unfamiliarity with the agile methodologies implying that the current business models in enterprise must be more aligned with the agile methodologies.

Originality/value

While there are efforts to develop AEA frameworks, one of the major findings of the literature review conducted is that there is evident research gap in the literature on the perception and associated factors of the EA stakeholders on having an agile enterprise architecture. This paper attempts to fill this gap.
Information seeking and collaborative decision-making behaviour in consultancy project teams: a network theoretic viewpoint
Authors: Badi Sulafa , Ji Hanxiao , Ochieng Edward G.
Published: June 2021

Purpose

This study aims to examine how embeddedness influences consultants' information seeking when making decisions within a social network of relationships, and how these social networks evolve throughout the project delivery stages. The study is grounded in social network theory and examines embeddedness from three perspectives: structural (network cohesion), relational (tie strength in terms of friendship and knowledge awareness) and actor prominence.

Design/methodology/approach

A social network analysis (SNA) questionnaire was administered to a team of consultants working on a management consultancy project in Shanghai, China. The SNA measures of density, degree centrality and betweenness centrality were used to analyse relationship patterns among project team members, permitting comparison between the networks. Networks were also compared across the three project delivery stages of collect, consider and create.

Findings

Structural embeddedness was observed in the active information seeking behaviour among consultancy team members. The moderate network density of the self-organising information seeking networks across the project delivery stages ensures that the team remains connected but avoids information redundancy and overload. Relational embeddedness was evident through the multiplexity of ties among team members with overlapping friendship and information seeking relationships. The knowledge awareness network's sparseness indicates a team of autonomous knowledge workers with distributed expertise. Project managers were the most prominent actors across the three project delivery stages, underlining these actors' relational leadership role.

Practical implications

The study provides a deeper understanding of collaborative decision-making behaviours in dynamic-project environments. Limited attempts have been made to visualise and analyse the relationships involved in small consulting teams. The novelty of the network approach adopted stems from its ability to offer a structural view of the relationship among consultants, thus offering a distinctive and arguably more complete picture of consultancy team dynamics.

Originality/value

The study validates the social network theory of embeddedness in a real-world collaborative decision-making setting and provides a deeper understanding of information seeking behaviours for decision-making in dynamic-project environments. From a project management process viewpoint, the evolving nature of the information seeking network as it changes across the project stages with associated actors' roles was also visualised graphically, offering a distinctive and arguably more complete picture of consultancy team dynamics.
Industry 4.0 an empirical analysis of users’ intention in the automotive sector
Authors: Toni Martina , Renzi Maria Francesca , Pasca Maria Giovina , Guglielmetti Mugion Roberta , di Pietro Laura , Ungaro Veronica
Published: June 2021

Purpose

This paper aims to study the automotive 4.0 context to understand the consumers’ propensity towards high-tech automated cars. The paper analyses the antecedents that lead to the use of innovative vehicles. Theory of planned behaviour (TPB) is adopted and extended by including further constructs, such as environmental aspects and inhibitors.

Design/methodology/approach

The advent of smart technologies and the internet of things has given rise to several contributions that look at consumers’ intention towards innovation adoption in the automotive industry. Furthermore, this study rises from the growing interest that sustainable mobility achieved. Based on the previous technology acceptance models and particularly TPB, this paper develops a structured questionnaire. After a pilot survey, the final questionnaire was administered online through email and social media in the Italian context. Structural equation modelling technique has been used for analysing data and testing the conceptual model.

Findings

The number of questionnaires filled out was 310, with a sample composed of young adults, characterised by different addiction levels towards technology. The results explain the drivers that lead to accept and adopt high-tech automated vehicles. This topic is still under investigation and offers potential research opportunities, considering the evolution of the market and the consumers’ habits and needs. Future research studies in this area should focus on generalising the present findings in other countries. Moreover, once this technology starts to be adopted, other constructs could be discovered, investigated and included in the model.

Originality/value

Mobility has raised a growing interest with the fast increasing demand for sustainability and growth of innovative solutions embedded in mobility. This research explores the TPB model’s application and the relation between its constructs, environmental aspects, inhibitors and intention to adopt automated vehicles. On this strength, it is possible to identify each construct’s relevance for obtaining social consensus on the market.
Does the exchange rate overshoot in an emerging economy?
Authors: Aftab Muhammad , Rafique Amir , Lau Evan
Published: June 2021

Purpose

The sticky-price monetary model of exchange rate states the overshooting hypothesis as, exchange rate depreciation beyond its long-term value in response to an increase in money supply owing to the sticky nature of prices. Because of interest and relevance to policy, there is a huge extant literature on it but with mixed findings that suggest the need for further studies to refine the findings. Pakistan’s rupee exchange rate against the US dollar depreciated 128.44% over the period May 2007–December 2018. Considering this substantial decline in rupee's value, this study aims to examine either the rupee short-run value is over-shot of its long-term value.

Design/methodology/approach

This study uses a linear ARDL approach that segregates the short-run and long-run effects thus clarifying the premise of exchange rate overshooting. Furthermore, this study also uses nonlinear ARDL as a robustness check incorporating structural breaks.

Findings

Findings based on a linear model show evidence of exchange rate undershooting that means a positive money shock causes the exchange rate to appreciate. A nonlinear analysis also provides support to these findings. However, the increase in relative money supply has more such effect than that of a decrease in the relative money supply. Moreover, the authorities’ inclination to stabilize the exchange rate appreciates its short-run value.

Originality/value

This study substantiates the overshooting hypothesis literature by considering the role of asymmetric effects of exchange rate determinants and structural breaks that is a rare attempt in the extant literature.
Black African perceptions of entrepreneurial outcomes in the UK
Authors: Ojo Sanya
Published: June 2021

Purpose

This study aims to discover how ethnic entrepreneurs actually understand the performance of their business through clarification of key indicators they use in evaluating business success and failure.

Design/methodology/approach

The attribution of success and failure in business was investigated through in-depth interviews, bolstered by the self-determination theory, with some UK’s Black African entrepreneurs.

Findings

Findings suggest that ethnic entrepreneurs’ attribution of success and failure is not only subjectively constructed but also enacted through cultural symbolism. The combination of cultural and personal values provoked attitudinal idiosyncrasy that construes business failure as success.

Originality/value

The result offers valuable knowledge to academics/practitioners researching success and failure factors in the ethnic entrepreneurship field.
Strengthening social innovation in higher education institutes – an organizational change process involving staff and students
Authors: Prantl Judith , Freund Susanne , Kals Elisabeth
Published: June 2021

Purpose

In recent decades, higher education institutes (HEIs) have come under pressure to cooperate with society as a whole. This shift towards an increased focus on third mission and social innovation activities implies a substantial organizational change process for many HEIs, as they need to initiate both structural and cultural changes. This paper provides guidance for such change processes by examining the views and attitudes of academic and administrative staff, as well as students within the HEIs over a period in which the HEIs increase their focus on social innovation.

Design/methodology/approach

The study uses a longitudinal quantitative approach consisting of a survey of administrative and academic staff, as well as students at two German HEIs. The authors studied members’ attitudes towards third mission and social innovation activities (N= 3470).

Findings

Results suggest that the university members’ attitudes towards third mission and social innovation are positive but change to some extent over time. Different aspects shape the attitudes within the three groups (administrative staff, academic staff and students). Furthermore, attitudes vary among academic employees who are involved in the process and those who are not.

Practical implications

The findings provide useful information for university managers and anyone aiming to promote social innovation at HEIs.

Originality/value

The study examines how attitudes of university members change whenever social innovation takes place at HEIs. This study includes data on the participation and empowerment of all HEI members in view of the important role that HEIs can play as supporters of social innovation.
The effect of sustainability on foreign direct investment inflows: evidence from developing countries
Authors: Singh Neha , Kapuria Cheshta
Published: June 2021

Purpose

This paper aims to analyse, the issue concerning the quality of inward foreign direct investments (FDI) by empirically investigating the role of four sustainability determinants of FDI, namely, economic, environmental, social and governance using data from 22 developing countries of the Asian region over a period from 2000–2016.

Design/methodology/approach

The methodology adopted to achieve this purpose is dynamic panel estimation (two-step difference generalised method of moments) by developing three econometric models. The data is sourced from the World Development, Worldwide Governance Indicators, International Telecommunication Union and the United Nations Conference on Trade and Development.

Findings

The econometric results indicate that, in general, control of corruption, political stability and electricity consumption influence sustainable FDI favourably; and CO2 emissions lower the extent of sustainable FDI. The result underlines deficiencies in the information technology aspect, which has a non-significant yet positive relationship with sustainable FDI. A pertinent finding of this study is that the past value of FDI inflows increases the current year’s FDI inflows in developing countries.

Practical implications

The findings related to gender and information technology aspects found in this paper will be of interest to both researchers and policymakers for substantially reorienting the sustainability attributes to foreign investment.

Originality/value

The authors’ main contributions are to encapsulate the conceptual framework into an empirical model by combining all the four dimensions, namely, environmental, economic, social and governance for developing countries.
Reduced expression of programmed cell death 1 and programmed cell death ligand 1 in infiltrating inflammatory cells of lichen planus without administration of immune checkpoint inhibitors
Authors: Shirouchi Kazufumi , Koshikawa Sachiko , Shinya Koichiro , Watanabe Hideaki , Izumi Miki , Yoshimura Kiyoshi , Sueki Hirohiko
Published: June 2021

Keratinocytes are the main targets of infiltrating T cells in the pathogenesis of lichen planus. However, the mechanisms of dense inflammatory infiltrates beneath the epidermis remain unknown. The aim of the present study was to clarify the roles of programmed cell death 1 (PD‐1) and its ligand (PD‐L1) in the pathogenesis of lichen planus. Immunohistochemistry of PD‐1 and PD‐L1 in 12 cases each of lichen planus and dermal‐type erythema multiforme was performed. The expression of PD‐1 and PD‐L1 on infiltrating inflammatory cells, predominantly lymphocytes in lichen planus, was significantly less compared to that in dermal‐type erythema multiforme. By dual immunofluorescence, the overlap between PD‐1 and leukocyte common antigen, CD4, CD8, CD68, and factor XIIIa was limited and found in only a very small portion of lichen planus cells. Our data suggest that decreased expression of PD‐1 and PD‐L1 could play a role in accelerating inflammatory cell infiltration targeting the epidermis in the pathogenesis of lichen planus.
The poultry pathogen Riemerella anatipestifer appears as a reservoir for Tet(X) tigecycline resistance
Authors: Umar Zeeshan , Chen Qiwei , Tang Biao , Xu Yongchang , Wang Jinzi , Zhang Huimin , Ji Kai , Jia Xu , Feng Youjun
Published: June 2021

The transferability of bacterial resistance to tigecycline, the ‘last‐resort’ antibiotic, is an emerging challenge of global health concern. The plasmid‐borne tet(X) that encodes a flavin‐dependent monooxygenase represents a new mechanism for tigecycline resistance. Natural source for an ongoing family of Tet(X) resistance determinants is poorly understood. Here, we report the discovery of 26 new variants [tet(X18) to tet(X44)] from the poultry pathogen Riemerella anatipestifer, which expands extensively the current Tet(X) family. R. anatipestifer appears as a natural reservoir for tet(X), of which the chromosome harbours varied copies of tet(X) progenitors. Despite that an inactive ancestor rarely occurs, the action and mechanism of Tet(X2/4)‐P, a putative Tet(X) progenitor, was comprehensively characterized, giving an intermediate level of tigecycline resistance. The potential pattern of Tet(X) dissemination from ducks to other animals and humans was raised, in the viewpoint of ecological niches. Therefore, this finding defines a large pool of natural sources for Tet(X) tigecycline resistance, heightening the need of efficient approaches to manage the inter‐species transmission of tet(X) resistance determinants.
Extent and Causes of Chesapeake Bay Warming
Authors: Hinson Kyle E. , Friedrichs Marjorie A.M. , St‐Laurent Pierre , Da Fei , Najjar Raymond G.
Published: June 2021

Coastal environments such as the Chesapeake Bay have long been impacted by eutrophication stressors resulting from human activities, and these impacts are now being compounded by global warming trends. However, there are few studies documenting long‐term estuarine temperature change and the relative contributions of rivers, the atmosphere, and the ocean. In this study, Chesapeake Bay warming, since 1985, is quantified using a combination of cruise observations and model outputs, and the relative contributions to that warming are estimated via numerical sensitivity experiments with a watershed–estuarine modeling system. Throughout the Bay’s main stem, similar warming rates are found at the surface and bottom between the late 1980s and late 2010s (0.02 ± 0.02°C/year, mean ± 1 standard error), with elevated summer rates (0.04 ± 0.01°C/year) and lower rates of winter warming (0.01 ± 0.01°C/year). Most (~85%) of this estuarine warming is driven by atmospheric effects. The secondary influence of ocean warming increases with proximity to the Bay mouth, where it accounts for more than half of summer warming in bottom waters. Sea level rise has slightly reduced summer warming, and the influence of riverine warming has been limited to the heads of tidal tributaries. Future rates of warming in Chesapeake Bay will depend not only on global atmospheric trends, but also on regional circulation patterns in mid‐Atlantic waters, which are currently warming faster than the atmosphere.
A Social Policy Theory of Everyday Borrowing: On the Role of Welfare States and Credit Regimes
Authors: Wiedemann Andreas
Published: June 2021

Debt has become an essential part of many people's daily lives. This article develops a new comparative political economy perspective on the relationship between welfare states and household borrowing. I argue that the ways in which welfare states distribute benefits, and credit regimes provide access to credit, affect how individuals address social risks and, as a consequence, shape patterns of indebtedness. Permissive credit regimes substitute for social policies in limited welfare states, pushing economically disadvantaged groups into debt. Alternatively, credit markets complement social policies in the provision of financial liquidity in comprehensive welfare states, protecting vulnerable groups through government benefits while allowing less‐protected affluent groups to borrow money. In restrictive regimes, people instead rely on savings, expenditure cuts, and family support. I test these arguments using an original measure of credit regime permissiveness, cross‐national survey data, and full‐population administrative records from Denmark and panel data from the United States.
Effect of second‐trimester sonographic cervical length on the risk of spontaneous preterm delivery in different risk groups: A prospective observational multicenter study
Authors: Wikström Tove , Hagberg Henrik , Jacobsson Bo , Kuusela Pihla , Wesström Jan , Lindgren Peter , Fadl Helena , Wennerholm Ulla‐Britt , Valentin Lil
Published: June 2021

Introduction

The aim of the study is to compare the effect of cervical length measured with transvaginal ultrasound in the second trimester on the risk of spontaneous preterm delivery (PTD) between different risk groups of asymptomatic women with a singleton pregnancy.

Material and methods

This is a pre‐planned exploratory analysis of the CERVIX study, a prospective blinded multicenter diagnostic accuracy study. Asymptomatic women with a singleton pregnancy were consecutively recruited at their second‐trimester routine ultrasound examination at seven Swedish ultrasound centers. Cervical length was measured with transvaginal ultrasound at 18–20 weeks (Cx1; n = 11 072) and 21–23 weeks (Cx2, optional; n = 6288). The effect of cervical length on the risk of spontaneous PTD and its discriminative ability was compared between women with: (i) previous spontaneous PTD, late miscarriage or cervical conization (high‐risk group; n = 1045); (ii) nulliparae without risk factors (n = 5173); (iii) parae without risk factors (n = 4740). Women with previous indicated PTD were excluded (n = 114). Main outcome measures were: effect of cervical length on the risk of spontaneous PTD expressed as odds ratio per 5‐mm decrease in cervical length with interaction analysis using logistic regression to test whether the effect differed between groups, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, number needed to screen to detect one spontaneous PTD.

Results

The effect of cervical length at Cx2 on the risk of spontaneous PTD <33 weeks was similar in all groups (odds ratios 2.26–2.58, interaction p value 0.91). The discriminative ability at Cx2 was superior to that at Cx1 and was similar in all groups (AUC 0.69–0.76). Cervical length ≤25 mm at Cx2 identified 57% of spontaneous preterm deliveries <33 weeks in the high‐risk group with number needed to screen 161. The number needed to screen for groups (ii) and (iii) were 1018 and 843.

Conclusions

The effect of cervical length at 21–23 weeks on the risk of spontaneous PTD <33 weeks is similar in high‐ and low‐risk pregnancies. The differences in number needed to screen should be considered before implementing a screening program.
Topical treatment of diabetic retinopathy: a systematic review
Authors: Thagaard Mikkel S. , Vergmann Anna S. , Grauslund Jakob
Published: June 2021

Diabetic retinopathy (DR) is the most common microvascular complication in diabetes and may cause severe visual impairment. Until late stages of DR, treatment options are limited. The aim of the present review was to investigate whether changes of DR might be influenced by topical treatment with eye drops. This systematic review included both randomized and non‐randomized human clinical studies on the subject. A systematic search of PubMed Medline, Embase and Scopus databases yielded 710 studies. No inclusion criteria regarding classification of DR were defined. Reference lists as well as first authors were screened for the inclusion of additional studies. Potential bias of the randomized studies was assessed using the Cochrane Risk of Bias tool. Nineteen studies suitable for inclusion were identified. Seven studies were randomized trials. These examined 11 different pharmacological groups of drugs in DR. A favourable effect of corticosteroid eye drops in diabetic macular oedema (DMO) was reported in four studies, and another study reported a positive trend. Eye drops with non‐steroidal anti‐inflammatory drugs were also reported to have a favourable effect in DMO, but not in non‐center involving DMO. Application of neuroprotective agents was found effective in patients with pre‐existing neurodegeneration in three studies. The remaining studies of DMO and DR were heterogeneous in both designs and results. Studies on treatment of DR with topical eye drops vary with regards to patient population, interventional drugs, study design, and outcome measures. Treatment of DR with eye drops was found effective in the aforementioned cases, but there is still a need for further investigations of long‐term, randomized controlled trials in any of the reported pharmacological group.
Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N6‐methyladenosine methylation through methyltransferase‐like 14
Authors: Wang Shuo , Gan Meifu , Chen Chaoyi , Zhang Yi , Kong Jianlu , Zhang Honghe , Lai Maode
Published: June 2021

RNA N6‐methyladenosine (m6A) is an emerging regulatory mechanism for tumor progression in several types of cancer. However, the underlying regulation mechanisms of m6A methylation in colorectal cancer (CRC) remain unknown. Although the oncogenic function of methyl CpG binding protein 2 (MeCP2) has been reported, it is still unclear whether MeCP2 could alter RNA m6A methylation state. Here, we systematically identified MeCP2 as a prometastasis gene to regulate m6A methylation in CRC. Interestingly, MeCP2 could bind to methyltransferase‐like 14 (METTL14) to coregulate tumor suppressor Kruppel‐like factor 4 (KLF4) expression through changing m6A methylation modification. Furthermore, insulin‐like growth factor 2 mRNA‐binding protein 2 recognized the unique modified m6A methylation sites to enhance KLF4 mRNA stability. Taken together, these findings highlight the novel function of MeCP2 for regulating m6A methylation and reveal the underlying molecular mechanism for the interaction between MeCP2 and METTL14, which offers a better understanding of CRC progression and metastasis.
An EU budget of states and citizens
Authors: Crowe Richard
Published: June 2021

In a European Union of states and citizens, the budget of the Union continues to function principally as a budget between states. Despite various attempts over the decades to introduce reforms aimed at strengthening the connection with citizens, the budgetary system has shown itself to be resistant to change. However, the landmark agreements of 2020 on the new multiannual financial framework (MFF) 2021–2027, own resources and recovery plan (Next Generation EU [NGEU]) packages potentially open up new possibilities to move beyond the logic of juste retour and promote a more positive vision of European budgetary integration, founded on solidarity between states and citizens and coordinated action at all levels of governance. Building on the developments of 2020, this contribution assesses how the Conference on the Future of Europe might explore options to further strengthen the profile of the Union budget as a ‘budget of citizens’, as well as a ‘budget of states’.
Overcoming the growth–infectivity trade‐off in a bacteriophage slows bacterial resistance evolution
Authors: Zhang Quan‐Guo , Chu Xiao‐Lin , Buckling Angus
Published: June 2021

The use of lytic bacteriophages for treating harmful bacteria (phage therapy) is faced with the challenge of bacterial resistance evolution. Phage strains with certain traits, for example, rapid growth and relatively broad infectivity ranges, may enjoy an advantage in slowing bacterial resistance evolution. Here, we show the possibility for laboratory selection programs (“evolutionary training”) to yield phage genotypes with both high growth rate and broad infectivity, traits between which a trade‐off has been assumed. We worked with a lytic phage that infects the bacterium Pseudomonas fluorescens and adopted three types of training strategies: evolution on susceptible bacteria, coevolution with bacteria, and rotation between evolution and coevolution phases. Overall, there was a trade‐off between growth rate and infectivity range in the evolved phage isolates, including those from the rotation training programs. A small number of phages had both high growth rate and broad infectivity, and those trade‐off‐overcoming phages could slow or even completely prevent resistance evolution in initially susceptible bacterial populations. Our findings show the promise of well‐designed evolutionary training programs, in particular an evolution/coevolution rotation selection regime, for obtaining therapeutically useful phage materials.
Urban infrastructure influences dissolved organic matter quality and bacterial metabolism in an urban stream network
Authors: Arango Clay P. , Beaulieu Jake J. , Fritz Ken M. , Hill Brian H. , Elonen Colleen M. , Pennino Michael J. , Mayer Paul M. , Kaushal Sujay S. , Balz Adam D.
Published: June 2021

Urban streams are degraded by a suite of factors, including burial beneath urban infrastructure, such as roads or parking lots, which eliminates light and reduces direct organic matter inputs to streams from riparian zones. These changes to stream metabolism and terrestrial carbon contribution will likely have consequences for organic matter metabolism by microbes and dissolved organic matter (DOM) use patterns in streams. Respiration by heterotrophic biofilms drives the nitrogen and phosphorus cycles, but we lack a clear understanding of how stream burial and seasonality affect microbial carbon use.

We studied seasonal changes (autumn, spring, and summer) in organic matter metabolism by microbial communities in open and buried reaches of three urban streams in Cincinnati, OH. We characterised DOM quality using fluorescence spectroscopy and extracellular enzyme profiles, and we measured the respiration response to carbon supplements in nutrient diffusing substrata (NDS). We hypothesised: (1) that algal production would lead to higher quality DOM in spring compared to other seasons and in open compared to buried reaches, (2) lower reliance of microbial respiration on recalcitrant carbon sources in spring and in open reaches, and (3) that microbial respiration would increase in response to added carbon in autumn and in buried reaches.

Several fluorescence metrics showed higher quality DOM in spring than autumn, but only the metric of recalcitrant humic compounds varied by reach, with more humic DOM in open compared to buried reaches. This likely reflected open reaches as an avenue for direct terrestrial inputs from the riparian zone.

Extracellular enzyme assays showed that microbes in buried reaches allocated more effort to degrade recalcitrant carbon sources, consistent with a lack of labile carbon compounds due to limited photosynthesis. Nitrogen acquisition enzymes were highest in autumn coincident with riparian leaf inputs to the streams. Buried and open reaches both responded more strongly to added carbon in autumn when terrestrial leaf inputs dominated compared to the spring when vernal algal blooms were pronounced.

Our data show that stream burial affects the quality of the DOM pool with consequences for how microbes use those carbon sources, and that heterotrophic respiration increased on carbon‐supplemented NDS in buried and open stream reaches in both seasons. Different carbon quality and use patterns suggest that urban stream infrastructure affects spatiotemporal patterns of bacterial respiration, with likely consequences for nitrogen and/or phosphorus cycling given that carbon use drives other biogeochemical cycles. Management actions that increase light to buried streams could shift the balance between allochthonous and autochthonous DOM in urban streams with consequences for spatiotemporal patterns in bacterial metabolism.
Dendritic cell Flt3 – regulation, roles and repercussions for immunotherapy
Authors: Wilson Kayla R , Villadangos Jose A , Mintern Justine D
Published: June 2021

Dendritic cells (DCs) are essential for initiating immune responses. Depending on the environment, the type of DC and the way in which they interact with T cells, these immune responses can be beneficial or detrimental. DCs can be exploited as cellular vectors for vaccines against infection and cancer. The development and maintenance of DCs is dependent on the FMS‐like tyrosine kinase 3 (Flt3)/Flt3 ligand (Flt3L) signaling cascade. Flt3 is also one of the most commonly mutated genes in acute myeloid leukemia and as such represents an attractive drug target. In this review, Flt3 is discussed with a particular focus on DCs. We detail the lifecycle of Flt3, from transcription to degradation, and interrogate recent studies as to how this pathway can be manipulated for immunotherapy, vaccination and treatment of autoimmune disease.
Change of dental color and temperature through two bleaching agents boosted with light emitted by diodes
Authors: Álvarez‐Quiceno Daniela , Rojas‐Martínez Paola‐Andrea , Cruz‐González Alberto‐Carlos
Published: June 2021

Introduction

The use of light sources during the application of bleaching can reduce the time and improve the results, but at the same time this can increase the dental temperature. The objective of this study was to evaluate the performance of two bleaching agents and the increase in dental temperature with the use of light emitted by diodes (LED)‐unit.

Materials and methods

Forty third molars were obtained and randomized: the whiteness without lamp (WHN) and Pola office without lamp (PON) groups, two bleaching systems based on 35% hydrogen peroxide were used, according to manufacturer specifications. For the whiteness with lamp (WHL) and Pola office with lamp (POL) groups the same bleaching agents were light boosted. A spectrophotometer and ∆WID equation was used to record and analyzed teeth color. An infrared thermometer was used to record the external and internal temperature. A ∆T was obtained by the difference of the temperature of the groups with and without LED (WHN‐WHL and PON‐POL). For statistical analysis Kruskal‐Wallis test and Anova test were performed.

Results

The WHN, PON, WHL, and POL groups reported ∆WID values of 4.88 ± 1.08, 9.26 ± 3.27, 5.70 ± 2.48, 12.08 ± 5.44, respectively. The dates of internal temperature were 1.01 and 1.07°C, and for external temperature were 1.61 and 1.15°C respectively.

Conclusions

With the limitations of this study, both bleaching agents reported a significant increase in ∆WID with and without association of light. Significant temperature increases were also observed. The highest average temperature increase was approximately 1.61°C.

Clinical significance

Bleaching agents boosted with LED may improve the results of bleaching, but it is not essential to obtain good results.
Lipoprotein(a) and SARS‐CoV‐2 infections: Susceptibility to infections, ischemic heart disease and thromboembolic events
Authors: Di Maio Silvia , Lamina Claudia , Coassin Stefan , Forer Lukas , Würzner Reinhard , Schönherr Sebastian , Kronenberg Florian
Published: June 2021

Background

Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic.

Method

Cohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls.

Results

SARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n= 435,104) and SARS‐CoV‐2 positive patients (n= 6937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interactionp‐value = 0.03). Although SARS‐CoV‐2 positive patients had a five‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a).

Conclusions

SARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a).
Low Health Literacy Is Associated With Energy‐Balance‐Related Behaviors, Quality of Life, and BMI Among Rural Appalachian Middle School Students: A Cross‐Sectional Study
Authors: Reid Annie L. , Porter Kathleen J. , You Wen , Kirkpatrick Brittany M. , Yuhas Maryam , Vaught Shannon S. , Zoellner Jamie M.
Published: June 2021

BACKGROUND

Many studies document associations between low health literacy (HL) and poor health behaviors and outcomes. Yet, HL is understudied among adolescents, particularly from underserved, rural communities. We targeted rural adolescents in this cross‐sectional study and explored relationships between HL and (1) energy‐balance‐related health behaviors and (2) body mass index (BMI) and quality of life (QOL).

METHODS

Surveys were administered to 7th graders across 8 middle schools in rural Appalachia. HL was assessed using the Newest Vital Sign. Energy‐balance‐related behaviors and QOL were assessed using validated instruments. Height and weight were objectively measured. Analyses were conducted using the Hodges‐Lehmann nonparametric median difference test.

RESULTS

Of the 854 adolescent students (mean age = 12; 55% female), 47% had limited HL. Relative to students with higher HL, students with lower HL reported significantly lower frequency of health‐promoting behaviors (water, fruit and vegetable intake, physical activity, sleep), higher frequency of risky health behaviors (sugar‐sweetened beverages, junk food, screen time), and had higher BMI percentiles and lower QOL (all p < .05).

CONCLUSIONS

Low HL is associated with energy‐balance‐related behaviors, BMI, and QOL among rural, Appalachian adolescents. Findings underscore the relevance of HL among rural middle school students and highlight implications for school health.