bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Testing Availability on Intentions to Isolate during the COVID-19 Pandemic: A Randomized Trial
Authors: Zhang Justin C. , Christensen Katherine L. , Leuchter Richard K. , Vangala Sitaram , Han Maria , Croymans Daniel M.
Published: March 2021

Background

Little information exists on how COVID-19 testing availability influences intentions to engage in risky behavior. Understanding the behavioral effects of testing availability may provide insight into the role of adequate testing on controlling viral transmission.

Objective

To evaluate the impact of testing availability on behavioral intention to self-isolate in a simulated scenario with participants who have been clinically diagnosed with COVID-19.

Methods

A total of 1400 participants were recruited from Amazon Mechanical Turk (MTurk) through a national, online, opt-in survey. Participants were randomized to one of three hypothetical scenarios. Each scenario asked participants to imagine having symptoms consistent with COVID-19 along with a clinical diagnosis from their physician. However, scenarios differed in their testing result: testing unavailable, positive test, or negative test. The primary outcome was intention to engage in high-risk COVID-19 behaviors, measured using an 11-item mean score (range 1-7) that was pre-registered prior to data collection. The randomized survey was conducted between July 23rd to July 29th, 2020.

Results

Out of 1194 respondents (41.6% male, 58.4% female) with a median age of 38.5 years, participants who had no testing available in their clinical scenario showed significantly greater intentions to engage in behavior facilitating COVID-19 transmission compared to those who received a positive confirmatory test result scenario (difference (SE): 0.14 (0.06), P=0.016), equating to an 11.1% increase in mean score risky behavior intentions. Intention to engage in behaviors that can spread COVID-19 were also positively associated with male gender, poor health status, and Republican party affiliation.

Conclusion

Testing availability appears to play an independent role in influencing behaviors facilitating COVID-19 transmission. Such findings shed light on the possible negative externalities of testing unavailability.

Trial Registration

Effect of Availability of COVID-19 Testing on Choice to Isolate and Socially Distance, NCT04459520, https://clinicaltrials.gov/ct2/show/NCT04459520
Transmission potential of FloridianAedes aegyptimosquitoes for dengue virus serotype 4: Implications for estimating local dengue risk
Authors: Stephenson Caroline J. , Coatsworth Heather , Kang Seokyoung , Lednicky John A. , Dinglasan Rhoel R.
Published: March 2021

Dengue virus serotype 4 (DENV-4) circulated inAedes aegyptiin 2016 and 2017 in Florida in the absence of human index cases, compelling a full assessment of local mosquito vector competence and DENV-4 risk. To better understand DENV-4 transmission risk in Florida, we used an expanded suite of tests to measure and compare the vector competence of both an established colony ofAe. aegypti(Orlando strain [ORL]) and a field-derived colony from Collier County, Florida in 2018 (COL) for a Haitian DENV-4 human field isolate and a DENV-4 laboratory strain (Philippines H241). We immediately noted that ORL saliva-positivity was higher for the field versus laboratory DENV-4 strains. In a subsequent comparison with the recent COL mosquito colony we also observed significantly higher midgut susceptibility of COL and ORL for the Haitian DENV-4 field strain, and significantly higher saliva-positivity rate for COL, although overall saliva virus titers were similar between the two. These data point to a potential midgut infection barrier for the DENV-4 laboratory strain for both mosquito colonies and that the marked difference in transmission potential estimates hinge on virus-vector combinations. Our study highlights the importance of leveraging an expanded suite of testing methods with emphasis on utilizing local mosquito populations and field relevant dengue serotypes and strains to accurately estimate transmission risk in a given setting.

Importance

DENV-4 was found circulating in Florida (FL)Ae. aegyptimosquitoes in the absence of human index cases in the state (2016-2017). How DENV-4 was maintained locally is unclear, presenting a major gap in our understanding of DENV-4 public health risk. We determined the baseline arbovirus transmission potential of laboratory and field colonies ofAe. aegyptifor both laboratory and field isolates of DENV-4. We observed high transmission potential of field populations ofAe. aegyptiand evidence of higher vertical transmission of the DENV-4 field isolate, providing clues to the possible mechanism of undetected DENV-4 maintenance in the state. Our findings also move the field forward in the development of best practices for evaluating arbovirus vector competence, with evidence that transmission potential estimates vary depending on the mosquito-virus combinations. These data emphasize the poor suitability of lab-established virus strains and the high relevance of field-derived mosquito populations in estimating transmission risk.
Rescue of two trafficking-defective variants of the neuronal glycine transporter GlyT2 associated to hyperekplexia
Authors: de la Rocha-Muñoz Andrés , Melgarejo Elena , Aragón Carmen , López-Corcuera Beatriz
Published: March 2021

Hyperekplexia is a rare sensorimotor syndrome characterized by pathological startle reflex in response to unexpected trivial stimuli for which there is no specific treatment. Neonates suffer from hypertonia and are at high risk of sudden death due to apnea episodes. Mutations in the humanSLC6A5gene encoding the neuronal glycine transporter GlyT2 may disrupt the inhibitory glycinergic neurotransmission and cause a presynaptic form of the disease. The phenotype of missense mutations giving rise to protein misfolding but maintaining residual activity could be rescued by facilitating folding or intracellular trafficking. In this report, we characterized the trafficking properties of two mutants associated with hyperekplexia (A277T and Y707C, rat numbering). Transporter molecules were partially retained in the endoplasmic reticulum showing increased interaction with the endoplasmic reticulum chaperone calnexin. One transporter variant had export difficulties and increased ubiquitination levels, suggestive of enhanced endoplasmic reticulum-associated degradation. However, the two mutant transporters were amenable to correction by calnexin overexpression. Within the search for compounds capable of rescuing mutant phenotypes, we found that the arachidonic acid derivative N-arachidonoyl glycine can rescue the trafficking defects of the two variants in heterologous cells and rat brain cortical neurons. N-arachidonoyl glycine improves the endoplasmic reticulum output by reducing the interaction transporter/calnexin, increasing membrane expression and improving transport activity in a comparable way as the well-established chemical chaperone 4-phenyl-butyrate. This work identifies N-arachidonoyl glycine as a promising compound with potential for hyperekplexia therapy.
Calcium-Permeable AMPA Receptor Activity and GluA1 Trafficking in the Basolateral Amygdala Regulate the Positive Reinforcing Effects of Alcohol
Authors: Faccidomo Sara , Cogan Elizabeth S , Hon Olivia J. , Hoffman Jessica L , Saunders Briana L , Eastman Vallari R , Kim Michelle , Taylor Seth M. , A McElligott Zoé , Hodge Clyde W
Published: March 2021

Addiction is viewed as maladaptive glutamate-mediated neuroplasticity that is regulated, in part, by calcium-permeable AMPA receptor (CP-AMPAR) activity. However, the contribution of CP-AMPARs to alcohol-seeking behavior remains to be elucidated. We evaluated CP-AMPAR activity in the basolateral amygdala (BLA) as a potential target of alcohol that also regulates alcohol self-administration in C57BL/6J mice. Operant self-administration of sweetened alcohol increased spontaneous EPSC frequency in BLA neurons that project to the nucleus accumbens as compared to behavior-matched sucrose controls indicating an alcohol-specific upregulation of synaptic activity. Bath application of the CP-AMPAR antagonist NASPM decreased evoked EPSC amplitude only in alcohol self-administering mice indicating alcohol-induced synaptic insertion of CP-AMPARs in BLA projection neurons. Moreover, NASPM infusion in the BLA dose-dependently decreased the rate of operant alcohol self-administration providing direct evidence for CP-AMPAR regulation of alcohol reinforcement. Since most CP-AMPARs are GluA1-containing, we asked if alcohol alters the activation state of GluA1-containing AMPARs. Immunocytochemistry results showed elevated GluA1-S831 phosphorylation in the BLA of alcohol as compared to sucrose mice. To investigate mechanistic regulation of alcohol self-administration by GluA1-containing AMPARs, we evaluated the necessity of GluA1 trafficking using a TET-ON AAV encoding a dominant-negative GluA1 c-terminus (GluA1ct) that blocks activity-dependent synaptic delivery of native GluA1-containing AMPARs. GluA1ct expression in the BLA reduced alcohol self-administration with no effect on sucrose controls. These results show that CP-AMPAR activity and GluA1 trafficking in the BLA mechanistically regulate the reinforcing effects of sweetened alcohol. Pharmacotherapeutic targeting these mechanisms of maladaptive neuroplasticity may aid medical management of alcohol use disorder.
Geometric properties of the Bertotti–Kasner space-time
Authors: Manjunatha H.M. , Narasimhamurthy S.K. , Nekouee Zohreh
Published: March 2021

Purpose

The purpose of this paper is to study the Bertotti–Kasner space-time and its geometric properties.

Design/methodology/approach

This paper is based on the features of λ-tensor and the technique of six-dimensional formalism introduced by Pirani and followed by W. Borgiel, Z. Ahsan et al. and H.M. Manjunatha et al. This technique helps to describe both the geometric properties and the nature of the gravitational field of the space-times in the Segre characteristic.

Findings

The Gaussian curvature quantities specify the curvature of Bertotti–Kasner space-time. They are expressed in terms of invariants of the curvature tensor. The Petrov canonical form and the Weyl invariants have also been obtained.

Originality/value

The findings are revealed to be both physically and geometrically interesting for the description of the gravitational field of the cylindrical universe of Bertotti–Kasner type as far as the literature is concerned. Given the technique of six-dimensional formalism, the authors have defined the Weyl conformal λW-tensor and discussed the canonical form of the Weyl tensor and the Petrov scalars. To the best of the literature survey, this idea is found to be modern. The results deliver new insight into the geometry of the nonstatic cylindrical vacuum solution of Einstein's field equations.
Management control structures and performance implications in international construction joint ventures: critical survey and conceptual framework
Authors: Tetteh Mershack Opoku , Chan Albert P.C. , Ameyaw Ernest Effah , Darko Amos , Yevu Sitsofe Kwame , Boateng Emmanuel B.
Published: March 2021

Purpose

Management control is needed in international joint ventures (IJVs) for successful management and performance. While IJV management control and performance concept has been widely explored, in the construction sector, the core understanding of the design of the two concepts is still lacking. This has resulted in the neglect of important questions and directions for research and practice improvement. This study aims to conduct a critical survey of prior studies addressing the conceptualization of management control and performance in IJVs and to propose a framework for studying the performance implications of management control in international construction joint ventures (ICJVs).

Design/methodology/approach

Using Scopus database and search terms, a systematic desktop search was conducted to retrieve empirically related peer-reviewed papers for this study.

Findings

Drawing on the transaction cost, institutional and relational logic, the first inclusive hypothetical model for studying the relationship between different dimensions of management control mechanism and multiple performance criteria in ICJVs is presented. The model proposes a measurement method for both the management control and performance and explains how they can be established in ICJVs.

Practical implications

The proposed framework provides a methodology to understand the dynamics of management control and performance implications in ICJV. Specifically, uncovering the critical paths will assist ICJV frontliners to approach management control in a more holistic and systematic way to promote achievement of ICJV goals.

Originality/value

The study gives a firm ground to the construction industry, which is accurate and educational for related fields concentrating on several other forms of cooperative relationships.
Technological foresight as support for the planning of research and development centers: the case of EI-UNAM
Authors: Castillo-Camarena Nadia , López-Ortega Eugenio
Published: March 2021

Purpose

This study aims to present a method to carry out technological foresight exercises in university technological research and development centers (TRDCs). The results support the organizational planning process.

Design/methodology/approach

The authors review the literature on the frameworks of foresight. The authors propose the use of quantitative (bibliometrics) and qualitative (expert meeting, Delphi) techniques. The authors apply this method to each research topic of interest of the TRDCs.

Findings

The application of the method to a research topic allows us to analyze the relevant knowledge areas for the development of that topic and its global trend. For each area, the authors identify the specific lines of research with the greatest growth and relevance. Considering these lines, the authors make a diagnosis of the TRDC situation regarding how to provide knowledge to decision-makers.

Research limitations/implications

The paper reviews the results of the application in the Engineering Institute of the National Autonomous University of Mexico and in the research topic “Seismic risks in civil engineering.” It is necessary to adjust the application of the method in other TRDCs to the conditions of the organization and to the development achieved by the TRDCs in the analyzed research topic.

Originality/value

There is no detailed literature on technological foresight exercises in university TRDCs that support the planning process of the organization. The method represents a proposal to establish priority research topics and specific research lines in research institutes, particularly universities. The authors present the application in a university TRDCs in Mexico.
Idea plagiarism detection with recurrent neural networks and vector space model
Authors: Nazir Azra , Mir Roohie Naaz , Qureshi Shaima
Published: March 2021

Purpose

Natural languages have a fundamental quality of suppleness that makes it possible to present a single idea in plenty of different ways. This feature is often exploited in the academic world, leading to the theft of work referred to as plagiarism. Many approaches have been put forward to detect such cases based on various text features and grammatical structures of languages. However, there is a huge scope of improvement for detecting intelligent plagiarism.

Design/methodology/approach

To realize this, the paper introduces a hybrid model to detect intelligent plagiarism by breaking the entire process into three stages: (1) clustering, (2) vector formulation in each cluster based on semantic roles, normalization and similarity index calculation and (3) Summary generation using encoder-decoder. An effective weighing scheme has been introduced to select terms used to build vectors based on K-means, which is calculated on the synonym set for the said term. If the value calculated in the last stage lies above a predefined threshold, only then the next semantic argument is analyzed. When the similarity score for two documents is beyond the threshold, a short summary for plagiarized documents is created.

Findings

Experimental results show that this method is able to detect connotation and concealment used in idea plagiarism besides detecting literal plagiarism.

Originality/value

The proposed model can help academics stay updated by providing summaries of relevant articles. It would eliminate the practice of plagiarism infesting the academic community at an unprecedented pace. The model will also accelerate the process of reviewing academic documents, aiding in the speedy publishing of research articles.
Fuzzy-logic-based support tools for initial screening of manufacturing reshoring decisions
Authors: Hilletofth Per , Sequeira Movin , Tate Wendy
Published: March 2021

Purpose

This paper investigates the suitability of fuzzy-logic-based support tools for initial screening of manufacturing reshoring decisions.

Design/methodology/approach

Two fuzzy-logic-based support tools are developed together with experts from a Swedish manufacturing firm. The first uses a complete rule base and the second a reduced rule base. Sixteen inference settings are used in both of the support tools.

Findings

The findings show that fuzzy-logic-based support tools are suitable for initial screening of manufacturing reshoring decisions. The developed support tools are capable of suggesting whether a reshoring decision should be further evaluated or not, based on six primary competitiveness criteria. In contrast to existing literature this research shows that it does not matter whether a complete or reduced rule base is used when it comes to accuracy. The developed support tools perform similarly with no statistically significant differences. However, since the interpretability is much higher when a reduced rule base is used and it require fewer resources to develop, the second tool is more preferable for initial screening purposes.

Research limitations/implications

The developed support tools are implemented at a primary-criteria level and to make them more applicable, they should also include the sub-criteria level. The support tools should also be expanded to not only consider competitiveness criteria, but also other criteria related to availability of resources and strategic orientation of the firm. This requires further research with regard to multi-stage architecture and automatic generation of fuzzy rules in the manufacturing reshoring domain.

Practical implications

The support tools help managers to invest their scarce time on the most promising reshoring projects and to make timely and resilient decisions by taking a holistic perspective on competitiveness. Practitioners are advised to choose the type of support tool based on the available data.

Originality/value

There is a general lack of decision support tools in the manufacturing reshoring domain. This paper addresses the gap by developing fuzzy-logic-based support tools for initial screening of manufacturing reshoring decisions.
The nexus between foreign bank presence and credit to the private sector: evidence from Sub-Saharan Africa
Authors: Fiador Vera , Amoah Lordina , Abbey Emmanuel
Published: March 2021

Purpose

The purpose of the study is to explore the implications of global financial integration on host economies in Sub-Saharan Africa (SSA). The study tests the competing views on the impact of foreign bank penetration on private sector access to credit in developing host economies.

Design/methodology/approach

Using data on a panel 25 SSA economies over a period of 22 years from 1995 to 2016, the study employs fixed effects and Prais-Winsten estimations as well as generalized methods of moments (GMM) to test the foreign bank impact.

Findings

The findings show support for the hypothesis that global financial integration has positive implications for participating economies. In other words, financial sector liberalization and deregulation leading to the influx of foreign banks has positive implications for access to credit by the private sector in SSA economies. The study also finds other standard determinants of access to credit like lending rate and broad money supply conforming to the existing literature in terms of impact.

Originality/value

Overall, the findings hold relevant implications for banking sector policies and the financial sector in general regarding the priority that policy makers and advisors attach to reforming financial sector policies.
Design and evaluation of exoskeleton for static conditions using Indian anthropometric considerations
Authors: C.R. Abhilash , Murali Sriraksha , Haq M. Abdul , Narahari N.S.
Published: March 2021

Purpose

Various occupations in life require personnel to stand for a prolonged period of time. This causes excessive stress on the joints leading to musculoskeletal disorders. This paper aims to design an equipment ensure the personnel rests on whenever necessary.

Design/methodology/approach

The method followed in this paper is the adoption of Karl Ulrich’s product design methodology with suitable modifications as per requirement. Human anthropometric data from the Indian population has been considered during the design and modelled according to it using computer aided design and computer aided engineering tools.

Findings

The conceptual equipment – exoskeleton designed sustained loads of human beings and proved to be a safe design in terms of the strength of the material used in the design.

Social implications

This design can serve as equipment, which helps the personnel with long-standing work hours to relieve themselves without actually sitting.

Originality/value

The design has been carefully crafted based on the inputs from the anthropometric features of human beings, which is completely passive in nature i.e. no use of external power is required for this exoskeleton compared to the other available designs.
Investigating the determinants and process of destination management system (DMS) implementation
Authors: Le Anh T. P. , Kunasekaran Puvaneswaran , Rasoolimanesh S. Mostafa , AriRagavan Neethiahnanthan , Thomas Toney K.
Published: March 2021

Purpose

This study aims to propose a comprehensive model to help understand factors influencing the intention to participate in a destination management system (DMS) amongst tourism stakeholders in Vietnam which are considered as the determinants of the successful implementation of the system.

Design/methodology/approach

A survey was conducted to investigate key stakeholders' opinions of participating in a DMS. In total, 301 questionnaires were used for analysis. Partial least squares structural equation modelling (PLS-SEM) was used to assess the measurement and structural models of the study.

Findings

Factors that influence various tourism stakeholders' intention to participate in the national DMS in Vietnam have been identified and examined. The results identify the important predictors of the tourism stakeholders' participation in the DMS including information quality, DMS operator readiness, government regulations and technology awareness. Interestingly, technology awareness was ascertained as a significant mediator for the relationship between performance expectancy, social influence, technology competency, competitive pressure and the intention to participate in the DMS.

Originality/value

This study has a unique theoretical contribution by developing a comprehensive model to predict the intention to participate in a DMS amongst tourism stakeholders with the modification and combination of three theoretical models and frameworks: the unified theory of acceptance and use of technology (UTAUT) model, technology–organisation–environment (TOE) framework and updated DeLone and McLean information systems (D&M IS) success model. It is expected to be a useful reference source for tourism management departments that want to develop DMSs in Vietnam. This model also can be used as an initial investigation for DMS implementation studies at other destinations.
Mutual monitoring in multi-period teams: an experimental investigation
Authors: Nikias Anthony , Sy Aida
Published: March 2021

Purpose

The purpose of this paper is to examine whether managers punish more and work harder in teams with peer monitoring when it is less costly to punish in a two-period, one-shot horizon.

Design/methodology/approach

An experiment is conducted in a two-period horizon with two treatments. The structure of performance measures makes it costless or costly to punish in the second period.

Findings

The results find punishing, contingent on first-period strategies, was significantly greater when it was costless compared to costly, as expected. Working, which is analogous to cooperating in prisoner dilemma games, was also significantly greater in the first and second periods when punishing was costless.

Practical implications

This paper is informative about the potential benefits of performance measures in dynamic team environments, which can be challenging and costly to develop. It adds insight into the design of self-discipline and tasks in teams which might help increase productivity.

Originality/value

This paper is related to the research on indefinite horizons, which attributes increases in cooperation to the existence of subgame perfect strategies to cooperate and potential gains from future cooperation. In comparison, this study examines the effects of the existence of subgame perfect strategies to work in isolation from the potential gains from future interactions. In addition, it examines whether their potential benefits depend on the cost of punishing when punishing is subgame perfect in a one-shot horizon.
Recommendation system for finding improved coworking area based on intelligent information technologies
Authors: Kotciuba Igor Yurievich , Shikov Alexey Nikolaevich , Voitekhovsky Yuri
Published: March 2021

Purpose

The purpose of this study is to make the implementation of a recommended Web service that allows one to formalize the search for a suitable coworking according to individual preferences as a decision-making task, as well as find a coworking area in an optimized setting for both the individual employee and those who carry out collective professional activities from a large number of alternatives in a shorter time.

Design/methodology/approach

In the implemented system of each place category in coworking areas, a search will be carried out according to formalized parameters and with an individual approach. To find the set of the required services of the coworking zone, the target functions of maximizing the priority of the place and minimizing the cost are determined, between which the user can set the ratio. As a constraint, the general fund of financial expenses for the time to reach the zone from different locations is used. The results of problem formalization are presented in the form of a mathematical model.

Findings

The use of a problem-oriented solution can significantly reduce the laboriousness of finding a suitable workspace.

Originality/value

The development of coworking zone practices contributes to the development of a professional infrastructure of the city and minimizes the cost of equipping each enterprise with additional tools, as well as manages labor resources and tracks trends of both professional and novice workers’ needs.
Application of photogrammetry in forensic pathology education of medical students in response to COVID‐19
Authors: Tóth Dénes , Petrus Karola , Heckmann Veronika , Simon Gábor , Poór Viktor Soma
Published: March 2021

As the coronavirus disease 2019 (COVID‐19) pandemic forced universities to switch to distance online education, there was an urgent need to find some virtual/digital alternatives in order to continue teaching. Opportunities such as watching pre‐recorded autopsy videos or creating and analyzing post‐mortem computed tomography or magnetic resonance imaging with various 3D surface imaging techniques are usually time‐consuming and cost‐intensive. Photogrammetry, which allows the creation of 3D textured surface models from a series of overlapping photographs taken from varying viewpoints, is a less common approach compared with post‐mortem imaging. We created 3D autopsy case models for a special online forensic pathology course in which students could try the models. Then, formal feedback was requested regarding the possible application of this method in education. Most of the students were satisfied with the new method and ranked photogrammetry higher than the other available methods. Our results indicate that photogrammetry has a high potential in undergraduate education, especially in the case of distance education or in those countries where declining autopsy rates have resulted in a decline in the use of the autopsy as an educational tool. Photogrammetry can also be used as a supplementary tool in traditional autopsy‐based education and has potential applications in various fields of medical education.
Study on Cizhou‐Style Inlaid Porcelain, the Northern Song Dynasty (960–1,127 AD), China
Authors: Ma D. , Zhao X. F. , Jiang X. C. Y. , Wang C. S. , Luo W. G.
Published: March 2021

The production of inlaid porcelain once prevailed in the Northern Song (960–1,127 AD) and Jin Dynasties (1,125–1,234 AD) across the north of China. During that time, the influence of the Cizhou kiln was considerable. However, we know little about the inlaying techniques used in ancient Chinese porcelain. In order to address this gap in knowledge, a total of seven pieces of inlaid porcelain sherds with the Cizhou style of the Northern Song Dynasty were analyzed by optical microscope (OM), X‐ray fluorescence spectrometry (XRF), X‐ray diffraction (XRD), and scanning electron microscope (SEM) in association with energy dispersive spectrometry (EDS). The results reveal that the material of inlay is identical with the slip, and the production process is also clearly shown. In addition, the international ceramic technological interaction of inlaid porcelain in Northeast Asia is discussed according to the analysis results.
Liver and kidney function in patients with Covid‐19 treated with remdesivir
Authors: van Laar Sylvia A. , de Boer Mark G. J. , Gombert‐Handoko Kim B. , Guchelaar Henk‐Jan , Zwaveling Juliette ,   LUMC‐Covid‐19 research group
Published: March 2021

For the treatment of Covid‐19 patients with remdesivir, poor renal and liver function were both exclusion criteria in randomized clinical trials and contraindication for treatment. Also, nephrotoxicity and hepatotoxicity are reported as adverse events. We retrospectively reviewed renal and liver functions of Covid‐19 103 patients who received remdesivir in the 15 days after treatment initiation. Approximately 20% of the patient population met randomized clinical trial exclusion criteria. In total, 11% of the patients had a decrease in estimated glomerular filtration rate >10 mL/min/1.73m2. Also, 25 and 35% had increased alanine transaminase and aspartate transaminase levels, respectively. However, serious adverse events were limited. Therefore, based on these preliminary results, contraindications based on kidney and liver function should not be absolute for remdesivir treatment in patients with Covid‐19 if these functions are monitored regularly. A larger patient cohort is warranted to confirm our results.
Primary post‐transplant lymphoproliferative disorder of the central nervous system: characteristics, management and outcome in 25 paediatric patients
Authors: Taj Mary M. , Maecker‐Kolhoff Britta , Ling Rebecca , Bomken Simon , Burkhardt Birgit , Chiang Alan K. S. , Csoka Monika , Füreder Anna , Haouy Stéphanie , Lazic Jelena , Miakova Natalia , Minard‐Colin Veronique , Turner Suzanne D. , Uyttebroeck Anne , Attarbaschi Andishe ,   the European Intergroup for Childhood Non‐Hodgkin’s Lymphoma (EICNHL), the international Berlin‐Frankfurt‐Münster (i‐BFM) Study Group
Published: March 2021

Primary central nervous system (CNS) post‐transplant lymphoproliferative disorder (PTLD) in childhood is rare. Twenty‐five patients were retrieved from nine European Intergroup for Childhood Non‐Hodgkin’s Lymphoma and/or international Berlin–Frankfurt–Münster Study Group members. Types of allografts included kidney (n = 11), liver (n = 4), heart (n = 5), bowel (n = 1) and haematopoietic stem cells (n = 4). Eighteen were male, 16 ≥ 10 years old, 21 had monomorphic disease and 24 solid intracranial tumour masses. Four‐year event‐free and overall survival rates were 50% ± 10% and 74% ± 9% respectively. This report represents the largest paediatric series of CNS PTLD reported to date, showing favourable survival odds following systemic and intrathecal chemotherapy and rituximab administration.
Glucagon‐like peptide‐1 (GLP‐1) receptor agonists and their cardiovascular benefits—The role of the GLP‐1 receptor
Authors: Helmstädter Johanna , Keppeler Karin , Küster Leonie , Münzel Thomas , Daiber Andreas , Steven Sebastian
Published: March 2021

Cardiovascular outcome trials revealed cardiovascular benefits for type 2 diabetes mellitus patients when treated with long‐acting glucagon‐like peptide‐1 (GLP‐1) receptor agonists. In the last decade, major advances were made characterising the physiological effects of GLP‐1 and its action on numerous targets including brain, liver, kidney, heart and blood vessels. However, the effects of GLP‐1 and receptor agonists, and the GLP‐1 receptor on the cardiovascular system have not been fully elucidated. We compare results from cardiovascular outcome trials of GLP‐1 receptor agonists and review pleiotropic clinical and preclinical data concerning cardiovascular protection beyond glycaemic control. We address current knowledge on GLP‐1 and receptor agonist actions on the heart, vasculature, inflammatory cells and platelets, and discuss evidence for GLP‐1 receptor‐dependent versus independent effects secondary of GLP‐1 metabolites. We conclude that the favourable cardiovascular profile of GLP‐1 receptor agonists might expand their therapeutic use for treating cardiovascular disease even in non‐diabetic populations.

LINKED ARTICLES

This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
How social start‐ups avoid being falling stars when developing social innovation
Authors: Battistella Cinzia , Dangelico Rosa Maria , Nonino Fabio , Pessot Elena
Published: March 2021

The aim of this study is to provide new insights into the social innovation (SI) development process in the context of social start‐ups. A multiple case study identifies the issues and mechanisms for social start‐ups to develop a social need into a potentially scalable innovation and to validate and scale it up, while avoiding a possible failure. Results show that key challenges faced by social start‐ups can be characterized according to the stage of the SI development path. Firstly, social start‐ups' failure can be caused by the lack of expertise in social problems and of flexible processes for social ventures creation; secondly, by the lack of awareness of SI benefits and proper resources allocation; and, finally, by a weak understanding of the impact and intangible outcomes of the developed SI in society, while ensuring its economic sustainability. Successfully overcoming these challenges requires social start‐ups to put in place the following mechanisms: (1) leveraging a vision and motivations that balance tensions in terms of the radical, economic and cultural aspects of SI; (2) engaging the SI stakeholders in different (and sequential) phases of SI development process; and (3) identifying and adopting the most suitable technological, financial and communication tools in an integrated way.
Synthesis of 2‐Chloro‐3‐amino indenone derivatives and their evaluation as inhibitors of DNA dealkylation repair
Authors: Nigam Richa , Raveendra Babu Kaki , Ghosh Topi , Kumari Bhavini , Das Prolay , Anindya Roy , Ahmed Khan Faiz
Published: March 2021

DNA alkylation damage, emanating from the exposure to environmental alkylating agents or produced by certain endogenous metabolic processes, affects cell viability and genomic stability. Fe(II)/2‐oxoglutarate‐dependent dioxygenase enzymes, such as Escherichia coli AlkB, are involved in protecting DNA from alkylation damage. Inspired by the natural product indenone derivatives reported to inhibit this class of enzymes, and a set of 2‐chloro‐3‐amino indenone derivatives was synthesized and screened for their inhibitory properties against AlkB. The synthesis of 2‐chloro‐3‐amino indenone derivatives was achieved from 2,3‐dichloro indenones through addition–elimination method using alkyl/aryl amines under catalyst‐free conditions. Using an in vitro reconstituted DNA repair assay, we have identified a 2‐chloro‐3‐amino indenone compound 3o to be an inhibitor of AlkB. We have determined the binding affinity, mode of interaction, and kinetic parameters of inhibition of 3o and tested its ability to sensitize cells to methyl methanesulfonate that mainly produce DNA alkylation damage. This study established the potential of indenone‐derived compounds as inhibitors of Fe(II)/2‐oxoglutarate‐dependent dioxygenase AlkB.
Long term clinical performance of 10 871 dental implants with up to 22 years of follow‐up: A cohort study in 4247 patients
Authors: French David , Ofec Ronen , Levin Liran
Published: March 2021

Background

The present retrospective study was aimed to assess the long‐term clinical performance of dental implants in a cohort study of 4247 patients.

Methods

A longitudinal observational cohort study was done on all implants performed by a single periodontist from July 1995 to April 2019. The main outcome variables of this study were implant failure and marginal bone level around implants.

Results

The study participants received a total of 10 871 implants with a mean of 2.56 implants per patient. The cohort was followed‐up to 22.2 years (mean = 4.5 ± 4.2). Among the 4247 patients of the current study, 140 patients (3.3%) experienced a combined total of 178 implant failures. According to life table analysis, at the implant level the cumulative survival rate at 3, 5, 10, and 15 years was 98.9%, 98.5%, 96.8%, and 94.0%, respectively while at patient level was 97.4%, 96.7%, 92.5%, and 86% at 3, 5, 10, and 15 years. Patients with multiple units were at a greater risk for having an implant failure. Baseline bone level was 0.09 ± 0.28 mm while at 8–10 years the mean bone level was 0.49 ± 0.74 mm. The incidence of peri‐implant mucositis at the implant level was 9.4% at 2–3 years, 9.3% at 4–5 years, 12.1% at 6–7 years, and 11.9% at 8–10 years. The incidence of peri‐implantitis was 2%, 2.6%, 3.2%, and 7.1% at 2–3, 4–5, 6–7, and 8–10 years, respectively. Cigarette smoking and diabetes mellitus were positively correlated with implant failure.

Conclusions

Though the results are promising and encouraging in terms of survival and bone level over time, it is important to emphasize the potential risk factors and consider them prior to dental implant placement.
An evaluation of the safety and preliminary efficacy of peri‐ and post‐operative treprostinil in preventing ischemia and reperfusion injury in adult orthotopic liver transplant recipients
Authors: Almazroo Omar Abdulhameed , Miah Mohammad Kowser , Pillai Venkateswaran C. , Shaik Imam H. , Xu Ruichao , Dharmayan Stalin , Johnson Heather J. , Ganesh Swaytha , Planinsic Raymond M. , Demetris Anthony J , Al‐Khafaji Ali , Lopez Roberto , Molinari Michele , Tevar Amit D. , Hughes Christopher , Humar Abhinav , Venkataramanan Raman
Published: March 2021

Background

Orthotopic liver transplantation (OLT) is the only treatment option for various end‐stage liver diseases. Ischemia and reperfusion (I/R) injury is one of the unavoidable complications/conditions in OLT. In 2019, a total of 8896 livers were transplanted of which >94% organs were procured from deceased donors. An increase in the use of extended criteria donor (ECD) livers for transplantation further unraveled the role of hepatic I/R injury on short‐term and long‐term graft outcomes. Despite promising outcomes with the use of antioxidants, free radical scavengers, and vasodilators; I/R‐mediated liver injury persists and significantly influences the overall clinical outcomes. Treprostinil, a synthetic prostacyclin I2 (PGI2) analog, due to its vasodilatory property, antiplatelet activity, and its ability to downregulate pro‐inflammatory cytokines can potentially minimize I/R injury.

Aim

We investigated the safety and preliminary efficacy of continuous intravenous infusion of treprostinil in liver transplant recipients in a prospective, single‐center, non‐randomized, interventional study.

Material and methods

This was a dose escalation (3 + 3 design) phase 1/2 study. Deceased donor liver transplant recipients received 5 ng/kg/min for two days, or 2.5, 5, and 7.5 ng/min/kg for 5 days as a continuous infusion. Multiple blood samples were collected for biochemical parameter assessment and for measuring treprostinil levels. Indocyanine green plasma disappearance rate was used as a measure of hepatic functional capacity.

Results

Subjects tolerated continuous infusion of treprostinil up to 5 ng/kg/min for 120 h with no occurrence of primary graft non‐function (PNF), minimized need for ventilation support, reduced hospitalization time, 100% graft and patient survival, and improved hepatobiliary excretory function comparable to normal healthy adults.

Discussion

Treprostinil can be administered to liver transplant patients safely during the perioperative period.

Conclusion

Based on this phase 1/2 study, further efficacy studies of treprostinil in preventing I/R injury of liver should be conducted to potentially increase the number of livers available for transplantation.
Efficiency of a novel gel product for duodenal ulcer bleeding
Authors: Miyamoto Shuichi , Suzuki Kazuharu , Kinoshita Kenji
Published: March 2021

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Precision medicine for genetic childhood movement disorders
Authors: Soo Audrey K S , Ferrini Arianna , Kurian Manju A
Published: March 2021

Increasingly effective targeted precision medicine is either already available or in development for a number of genetic childhood movement disorders. Patient‐centred, personalized approaches include the repurposing of existing treatments for specific conditions and the development of novel therapies that target the underlying genetic defect or disease mechanism. In tandem with these scientific advances, close collaboration between clinicians, researchers, affected families, and stakeholders in the wider community will be key to successfully delivering such precision therapies to children with movement disorders.

What this paper adds

Precision medicine for genetic childhood movement disorders is developing rapidly.

Accurate diagnosis, disease‐specific outcome measures, and collaborative multidisciplinary work will accelerate the progress of such strategies.
Visual processing speed is linked to functional connectivity between right frontoparietal and visual networks
Authors: Küchenhoff Svenja , Sorg Christian , Schneider Sebastian C. , Kohl Oliver , Müller Hermann J. , Napiórkowski Natan , Menegaux Aurore , Finke Kathrin , Ruiz‐Rizzo Adriana L.
Published: March 2021

Visual information processing requires an efficient visual attention system. The neural theory of visual attention (TVA) proposes that visual processing speed depends on the coordinated activity between frontoparietal and occipital brain areas. Previous research has shown that the coordinated activity between (i.e., functional connectivity and “inter‐FC”) cingulo‐opercular (COn) and right‐frontoparietal (RFPn) networks is linked to visual processing speed. However, how inter‐FC of COn and RFPn with visual networks links to visual processing speed has not been directly addressed yet. Forty‐eight healthy adult participants (27 females) underwent resting‐state (rs‐)fMRI and performed a whole‐report psychophysical task. To obtain inter‐FC, we analyzed the entire frequency range available in our rs‐fMRI data (i.e., 0.01–0.4 Hz) to avoid discarding neural information. Following previous approaches, we analyzed the data across frequency bins (Hz): Slow‐5 (0.01–0.027), Slow‐4 (0.027–0.073), Slow‐3 (0.073–0.198), and Slow‐2 (0.198–0.4). We used the mathematical TVA framework to estimate an individual, latent‐level visual processing speed parameter. We found that visual processing speed was negatively associated with inter‐FC between RFPn and visual networks in Slow‐5 and Slow‐2, with no corresponding significant association for inter‐FC between COn and visual networks. These results provide the first empirical evidence that links inter‐FC between RFPn and visual networks with the visual processing speed parameter. These findings suggest that direct connectivity between occipital and right frontoparietal, but not frontoinsular, regions support visual processing speed.
Carbon cycle inverse modeling suggests large changes in fractional organic burial are consistent with the carbon isotope record and may have contributed to the rise of oxygen
Authors: Krissansen‐Totton Joshua , Kipp Michael A. , Catling David C.
Published: March 2021

Abundant geologic evidence shows that atmospheric oxygen levels were negligible until the Great Oxidation Event (GOE) at 2.4–2.1 Ga. The burial of organic matter is balanced by the release of oxygen, and if the release rate exceeds efficient oxygen sinks, atmospheric oxygen can accumulate until limited by oxidative weathering. The organic burial rate relative to the total carbon burial rate can be inferred from the carbon isotope record in sedimentary carbonates and organic matter, which provides a proxy for the oxygen source flux through time. Because there are no large secular trends in the carbon isotope record over time, it is commonly assumed that the oxygen source flux changed only modestly. Therefore, declines in oxygen sinks have been used to explain the GOE. However, the average isotopic value of carbon fluxes into the atmosphere–ocean system can evolve due to changing proportions of weathering and outgassing inputs. If so, large secular changes in organic burial would be possible despite unchanging carbon isotope values in sedimentary rocks. Here, we present an inverse analysis using a self‐consistent carbon cycle model to determine the maximum change in organic burial since ~4 Ga allowed by the carbon isotope record and other geological proxies. We find that fractional organic burial may have increased by 2–5 times since the Archean. This happens because O2‐dependent continental weathering of 13C‐depleted organics changes carbon isotope inputs to the atmosphere–ocean system. This increase in relative organic burial is consistent with an anoxic‐to‐oxic atmospheric transition around 2.4 Ga without declining oxygen sinks, although these likely contributed. Moreover, our inverse analysis suggests that the Archean absolute organic burial flux was comparable to modern, implying high organic burial efficiency and ruling out very low Archean primary productivity.