bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo capture of bacterial cells by remote guiding
Authors: Rybkin Iaroslav , Pinyaev Sergey , Sindeeva Olga , German Sergey , Koblar Maja , Pyataev Nikolay , Čeh Miran , Gorin Dmitry , Sukhorukov Gleb , Lapanje Aleš
Published: August 2021

Recently, it has been shown that several bacterial strains can be very efficient in cancer treatment since they possess many important properties such as self-targeting, ease of detection, sensing and toxicity against tumors. However, there are only a few relevant “candidates” for such an approach, as targeting and detection one of the biggest challenges as well as there are many limitations in the use of genetic approaches. Here, it is proposed the solution that enables surface modification of alive bacterial cells without interfering with their genetic material and potentially reduces their toxic side effect. By the electrostatic interaction fluorescently labeled polyelectrolytes (PEs) and magnetite nanoparticles (NPs) were deposited on the bacterial cell surface to control the cell growth, distribution and detection of bacteria. According to the results obtained in vivo, by the magnet entrapment of the modified bacteria the local concentration of the cells was increased more than 5 times, keeping the high concentrations even when the magnet is removed. Since the PEs create a strong barrier, in vitro it was shown that the division time of the cells can be regulated for better immune presentation.
RIG-I-induced innate antiviral immunity protects mice from lethal SARS-CoV-2 infection
Authors: Marx Samira , Kümmerer Beate M. , Grützner Christian , Kato Hiroki , Schlee Martin , Bartok Eva , Renn Marcel , Hartmann Gunther
Published: August 2021

The SARS-CoV-2 pandemic has underscored the need for rapidly employable prophylactic and antiviral treatments against emerging viruses. Nucleic acid agonists of the innate immune system can be administered to activate an effective antiviral program for prophylaxis in exposed populations, a measure of particular relevance for SARS-CoV-2 infection due to its efficient evasion of the host antiviral response. In this study, we utilized the K18-hACE2 mouse model of COVID-19 to examine whether prophylactic activation of the antiviral receptor RIG-I protects mice from SARS-CoV-2 infection. Systemic treatment of mice with a specific RIG-I ligand one to seven days prior to infection with a lethal dose of SARS-CoV-2 improved their survival of by up to 50 %. Improved survival was associated with lower viral load in oropharyngeal swabs and in the lungs and brain of RIG-I-treated mice. Moreover, despite antiviral protection, the surviving mice that were treated with RIG-I ligand developed adaptive SARS-CoV-2-specific immunity. These results reveal that prophylactic RIG-I activation by synthetic RNA oligonucleotides is a promising strategy to convey short-term, unspecific antiviral protection against SARS-CoV-2 infection and may be a suitable broad-spectrum approach to constraining the spread of newly emerging viruses until virus-specific therapies and vaccines become available.
Diversity of Antibiotic Resistance genes and Transfer Elements-Quantitative Monitoring (DARTE-QM): a method for detection of antimicrobial resistance in environmental samples
Authors: Smith Schuyler D. , Choi Jinlyung , Ricker Nicole , Yang Fan , Hinsa-Leasure Shannon , Soupir Michelle , Allen Heather , Howe Adina
Published: August 2021

Effective monitoring of antibiotic resistance genes and their dissemination in environmental ecosystems has been hindered by the cost and efficiency of methods available for the task. We developed a method entitled the Diversity of Antibiotic Resistance genes and Transfer Elements-Quantitative Monitoring (DARTE-QM), a system implementing high-throughput sequencing to simultaneously sequence thousands of antibiotic resistant genes representing a full-spectrum of antibiotic resistance classes commonly seen in environmental systems. In this study, we demonstrated DARTE-QM by screening 662 antibiotic resistance genes within environmental samples originated from manure, soil, and animal feces, in addition to a mock-community used as a control to test performance. DARTE-QM offers a new approach to studying antibiotic resistance in environmental microbiomes, showing advantages in efficiency and the ability to scale for many samples. This method provides a means of data acquisition that will alleviate the obstacles that many researchers in this area currently face.
Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle
Authors: Omini Joy , Wojciechowska Izabela , Skirycz Aleksandra , Moriyama Hideaki , Obata Toshihiro
Published: August 2021

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle ‘metabolon’ which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was presented together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways.
Environmental DNA from a small sample of reservoir water can tell volumes about its biodiversity
Authors: Torres André lq , Do Amaral Danielle Las , Guimaraes Murilo , Pinheiro Henrique B , Pereira Camila M , De Castro Giovanni M , Guerreiro Luana Ta , Americo Juliana A , Rebelo Mauro F
Published: August 2021

We evaluated the potential of metabarcoding in assessing the environmental DNA (eDNA) biodiversity profile in the water column of an hydroelectric power plant reservoir in southeast Brazil. Samples were obtained in three technical replicates at 1 km from the dam at 1, 13 and 25 m depths. For each minibarcodes -- COI, 12S and 16S -- 1.5 million paired-reads (150 base pairs) were sequenced. A total of 44 unique taxa were found. COI identified most of the taxa (34 taxa; 77.2 %) followed by 16S (14; 31.8 %) and 12S (10; 22.7 %). All minibarcodes identified fishes (13 taxa), however, COI detected other aquatic macro-invertebrates (18), algae (3) and amoebas (2). Richness was the same across the three depths (35 taxa), although, beta diversity suggested slightly divergent profiles. In just one location we identified 15 taxa never reported previously, 50% of the fish species identified in the last year of fishery monitoring and 13% of the species in biodiversity surveys performed from 2012 to 2021. Clustering into Amplicon Sequence Variants (ASV) showed that 12S and 16S are able to detect predominant haplotypes of fishes, suggesting they are suitable to study population genetics of this group. In this study we reviewed the species occurring within the Três Irmãos reservoir according to previous conventional surveys and demonstrated that eDNA metabarcoding can be applied to monitor its biodiversity.
Accelerated Partner Therapy contact tracing intervention for people with chlamydia: the LUSTRUM process evaluation using programme theory
Authors: Flowers Paul , Mapp Fiona , McQueen Jean , Nandwani Rak ,   The LUSTRUM programme, Estcourt Claudia
Published: August 2021

Background

Using programme theory we report a process evaluation of Accelerated Partner Therapy (APT) - a novel contact tracing (partner notification) intervention for people with chlamydia as part of the LUSTRUM trial.

Methods

Following the specification and visualisation of initial programme theory, questions of context dependency, fidelity, and functioning of putative intervention mechanisms were addressed using deductive thematic analysis of qualitative data collected through focus groups and individual interviews with purposively sampled health care professionals (n=34 from ten sites), index patients (n=15), and sex partners who received APT (n=17). Analyses were independent of trial results.

Results

APT was anticipated to change key interactions and sexual health service organisation to accommodate safe and optimal remote care. APT training and resources transformed key interactions as anticipated. Overall intervention fidelity was good and APT was well-liked by those who delivered and received it. Putative intervention mechanisms worked mostly as expected although those concerned with local implementation sometimes worked counter to expectations. APT and its trial struggled to be implemented at scale across all sites. Considerable pressures drove services to constantly adapt to achieve efficiencies. APT was perceived as time consuming without visible impact on perceived patient numbers in clinic curtailing positive feedback loops driving normalisation.

Discussion

Using programme theory we show an evidence-based, theoretically informed, overview of how APT worked dynamically within the context of the trial and within UK sexual health services. We find a mixed picture of a well-liked, intuitive, coherent intervention struggling to gain purchase within an already pressured service.

Trial registration

ISRCTN15996256

Study protocol

doi.org/10.1136/bmjopen-2019-034806

Ethical approval

This study received ethical approval from London—Chelsea Research Ethics Committee (18/LO/0773). Findings will be published with open access licences.

Funding

This work presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (reference number RP-PG-0614-20009).
Spatiotemporal dynamics of human microglia are linked with brain developmental processes across the lifespan
Authors: Menassa D.A. , Muntslag T.A.O. , Martin-Estebané M. , Barry-Carroll L. , Chapman M.A. , Adorjan I. , Tyler T. , Turnbull B. , Rose-Zerilli M.J.J. , Nicoll J.A.R. , Krsnik Z. , Kostovic I. , Gomez-Nicola D.
Published: August 2021

Microglia, the brain’s resident macrophages, shape neural development and wiring, and are key neuroimmune hubs in the pathological signature of neurodevelopmental disorders. In the human brain, microglial development has not been carefully examined yet, and most of our knowledge derives from rodents. We established an unprecedented collection of 97 postmortem tissues enabling quantitative, sex-matched, detailed analysis of microglial across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing novel waves in microglial density across gestation and infancy, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNAseq and single-cell RNAseq datasets. This study provides unparalleled insight and detail into the spatiotemporal dynamics of microglia across the human lifespan. Our findings serve as a solid foundation for elucidating how microglia contribute to shaping neurodevelopment in humans.
A blended learning strategy: reimagining the post-Covid-19 architectural education
Authors: Megahed Naglaa , Hassan Asmaa
Published: August 2021

Purpose

The present work reviews the impacts of the Covid-19 pandemic on architecture education (AE), with the aim of discussing the interaction and integration of technology-based models.

Design/methodology/approach

Different research methods were used to achieve the research purposes including an online survey, semistructured interviews, observations and reviewing recent literature. The study proposes a theoretical framework to investigate blended learning (BL) approaches in AE, based on the blended teaching–learning continuum, the growth of online delivery mode and technology integration and the gradual responsibility adopted for the current Covid-19 pandemic.

Findings

The study proposes a vision to reimagine post-Covid-19 education and the required BL strategy to provide a theoretical framework that integrates the instructional models required to be investigated by instructors.

Research limitations/implications

The research findings are based on a theoretical approach not tested practically. A further detailed investigation is required. Thus, the road to reimagining the post-Covid-19 AE is still evolving.

Social implications

As faculty members, one should take steps toward preparing BL strategies. These strategies present other alternatives to continue teaching and learning while keeping safe in any other emergency in education. In this work, an overview of BL approaches, continuum and related technological and instructional models has been shaped to propose a new vision to post-Covid-19 AE.

Originality/value

This paper responds directly to the initiated call on the pandemic's effect on traditional education by taking a pedagogical perspective. The study presents a holistic BL strategy and proposes a new theoretical and instructional model to design a suitable and balanced BL environment in AE.
The promise of a four-day week? A critical appraisal of a management-led initiative
Authors: Delaney Helen , Casey Catherine
Published: August 2021

Purpose

This article critically investigates a management-led experiment to institute a four-day work week with stated intentions of improving productivity and worker wellbeing. The article analyses the framing and implementation of the reduced work hours (RWH) trial, the responses of employees and the outcomes and implications of the trial. It raises concerns regarding the managerial appropriation of employee aspirations for more autonomy over time and improved work life.

Design/methodology/approach

We conducted a qualitative case study of a medium-sized company operating in the financial services sector in New Zealand. Focus groups and semi-structured interviews were conducted with 45 employees.

Findings

Our study finds that the promise of a four-day week attracted employee favour and individualised benefits. However, entrenched managerialist practices of performance measurement, monitoring and productivity pressures were intensified. Pro-social and collective interests evident in labour-led campaigns were absent. We urge greater critical scrutiny into seemingly advantageous “business case” initiatives for reduced work hours.

Originality/value

Little is known about what happens to concern for social and employee interests entailed in reduced working hours initiatives when a management-led initiative is implemented. Indeed, the majority of research focuses on the macro-level rather than interrogating the “black box” of firms. Our inquiry contributes to these debates by asking, how does a management-led RWH initiative affect employees?
Predicting the effect of entrepreneurial stressors and resultant strain on entrepreneurial behaviour: an SEM-based machine-learning approach
Authors: Arshi Tahseen Anwer , Islam Sardar , Gunupudi Nirmal
Published: August 2021

Purpose

Considerable evidence suggests that although they overlap, entrepreneurial and employee stressors have different causal antecedents and outcomes. However, limited empirical data explain how entrepreneurial traits, work and life drive entrepreneurial stressors and create entrepreneurial strain (commonly called entrepreneurial stress). Drawing on the challenge-hindrance framework (CHF), this paper hypothesises the causal effect of hindrance stressors on entrepreneurial strain. Furthermore, the study posits that entrepreneurial stressors and the resultant strain affect entrepreneurial behaviour.

Design/methodology/approach

The study adopts an SEM-based machine-learning approach. Cross-lagged path models using SEM are used to analyse the data and train the machine-learning algorithm for cross-validation and generalisation. The sample consists of 415 entrepreneurs from three countries: India, Oman and United Arab Emirates. The entrepreneurs completed two self-report surveys over 12 months.

Findings

The results show that hindrances to personal and professional goal achievement, demand-capability gap and contradictions between aspiration and reality, primarily due to unique resource constraints, characterise entrepreneurial stressors leading to entrepreneurial strain. The study further asserts that entrepreneurial strain is a significant predictor of entrepreneurial behaviour, significantly affecting innovativeness behaviour. Finally, the finding suggests that psychological capital moderates the adverse impact of stressors on entrepreneurial strain over time.

Originality/value

This study contributes to the CHF by demonstrating the value of hindrance stressors in studying entrepreneurial strain and providing new insights into entrepreneurial coping. It argues that entrepreneurs cope effectively against hindrance stressors by utilising psychological capital. Furthermore, the study provides more evidence about the causal, reversed and reciprocal relationships between stressors and entrepreneurial strain through a cross-lagged analysis. This study is one of the first to evaluate the impact of entrepreneurial strain on entrepreneurial behaviour. Using a machine-learning approach is a new possibility for using machine learning for SEM and entrepreneurial strain.
Opportunities and challenges of using socially intelligent agents: increasing interaction and school participation for children suffering from a long-term illness
Authors: Mårell-Olsson Eva , Mejtoft Thomas , Tovedal Sofia , Söderström Ulrik
Published: August 2021

Purpose

Children suffering from cancer or cardiovascular disease, who need extended periods of treatment in hospitals, are subjected to multiple hardships apart from the physical implications, for example, experienced isolation and disrupted social and academic development. This has negative effects long after the child's recovery from the illness. The purpose of this paper is to examine the non-medical needs of children suffering from a long-term illness, as well as research the field of artificial intelligence (AI) – more specifically, the use of socially intelligent agents (SIAs) – in order to study how technology can enhance children's interaction, participation and quality of life.

Design/methodology/approach

Interviews were performed with experts in three fields: housing manager for hospitalized children, a professor in computing science and researcher in AI, and an engineer and developer at a tech company.

Findings

It is important for children to be able to take control of the narrative by using an SIA to support the documentation of their period of illness, for example. This could serve as a way of processing emotions, documenting educational development or keeping a reference for later in life. The findings also show that the societal benefits of AI include automating mundane tasks and recognizing patterns.

Originality/value

The originality of this study concerns the holistic approach of increasing the knowledge and understanding of these children's specific needs and challenges, particularly regarding their participation and interaction with teachers and friends at school, using an SIA.
Managing information asymmetry in public–private relationships undergoing a digital transformation: the role of contractual and relational governance
Authors: Aben Tom A.E. , van der Valk Wendy , Roehrich Jens K. , Selviaridis Kostas
Published: August 2021

Purpose

Inter-organisational governance is an important enabler for information processing, particularly in relationships undergoing digital transformation (DT) where partners depend on each other for information in decision-making. Based on information processing theory (IPT), the authors theoretically and empirically investigate how governance mechanisms address information asymmetry (uncertainty and equivocality) arising in capturing, sharing and interpreting information generated by digital technologies.

Design/methodology/approach

IPT is applied to four cases of public–private relationships in the Dutch infrastructure sector that aim to enhance the quantity and quality of information-based decision-making by implementing digital technologies. The investigated relationships are characterised by differing degrees and types of information uncertainty and equivocality. The authors build on rich data sets including archival data, observations, contract documents and interviews.

Findings

Addressing information uncertainty requires invoking contractual control and coordination. Contract clauses should be precise and incentive schemes functional in terms of information requirements. Information equivocality is best addressed by using relational governance. Identifying information requirements and reducing information uncertainty are a prerequisite for the transformation activities that organisations perform to reduce information equivocality.

Practical implications

The study offers insights into the roles of both governance mechanisms in managing information asymmetry in public–private relationships. The study uncovers key activities for gathering, sharing and transforming information when using digital technologies.

Originality/value

This study draws on IPT to study public–private relationships undergoing DT. The study links contractual control and coordination as well as relational governance mechanisms to information-processing activities that organisations deploy to reduce information uncertainty and equivocality.
India's tryst with Modi-fare 2014–19: towards a universalistic welfare regime
Authors: Nakray Keerty
Published: August 2021

Purpose

This paper examines India’s tryst with welfare/dis-fare with a specific focus on Modi Sarkar's (2014–2019) dirigiste style reforms. In the welfare regime research, Esping-Andersen (1990) classified advanced economies into three ideal-types of liberal, conservative-corporatist and social-democratic welfare states by government-led welfare provisions and levels of decommodification. The classical typology discussions include countries such as India which is classified as informal-insecurity regime due to a large informal economy with no social security for workers. Based on theoretical standpoints of the political economy of welfare states, comparative historical institutionalism and critical junctures this article examines Modifare has expanded formal welfare to its citizens.

Design/methodology/approach

The article uses crisp-set analysis to examine the social policy developments under Modi's regime in India.

Findings

This paper examines if the centre-right Modi government did bring about a radical departure from UPA I and II lacklustre welfare approach to the more strategic use of welfare reforms as a political weapon on a national scale. It concludes that Modi-fare falls short in being transformatory.

Originality/value

The article is an original contribution to the field of comparative welfare regimes.
Business, peacebuilding, violent conflict and sustainable development in Myanmar: presenting evidence from a new survey dataset
Authors: Miklian Jason , Barkemeyer Ralf
Published: August 2021

Purpose

This paper aims to present a new survey data set of 9,065 private sector respondents and other stakeholder groups, in Myanmar. The primary aim of this paper is to offer new insight avenues on local business–conflict–development interactions, and offer the full survey data set itself as an open-source research tool for scholars and practitioners.

Design/methodology/approach

The survey was conducted over smartphone in 2018. It asked questions that aimed to better understand the relationships between business, ethnic conflict, investment, corporate social responsibility and the United Nations sustainable development goals in Myanmar and in Rakhine State in particular.

Findings

The data set captures a series of significant differences in corporate leadership perspectives on the role of business in society, across sectors (e.g. banking, agriculture, retail, manufacturing, extractives) and variations across firm country of ownership (e.g. national firms, Global North firms, Indian firms, Chinese firms).

Research limitations/implications

The authors conclude with a brief discussion of possible research findings from the survey, offering suggestions for possible forward analysis. The authors offer here the raw survey data as an attachment for full global open-source use and application.

Practical implications

This data set offers a unique window into stakeholder perceptions and understandings of working through conflict, and the role of business in development in a fragile conflict-affected state (Myanmar). The authors also conduct two example analyses of the data set using ANOVA and Kruskal–Wallis tests to illustrate possible uses and findings of the data set.

Social implications

The authors briefly discuss social implications as well, particularly regarding the role of business in peacebuilding and development.

Originality/value

This data set offers a unique window into stakeholder perceptions and understandings of working through conflict, and the role of business in development in a fragile conflict-affected state (Myanmar). The authors also conduct two example analyses of the data set using ANOVA and Kruskal–Wallis tests to illustrate possible uses and findings of the data set.
Ethics and digital collections: a selective overview of evolving complexities
Authors: Mindel David
Published: August 2021

Purpose

Digital collections are becoming more commonplace at libraries, archives and museums around the world, creating potential for improved accessibility to information that may otherwise remain hidden and further support for intellectual exploration. As a result of the growing potential for digital collections to inform and influence, the conversation surrounding ethics and digital collections needs to be continually examined and adapted as technologies evolve, user expectations change and digital information plays an increasing role in our everyday lives. In this context, this paper presents an overview of multifaceted ethical realities that impact the how, why and what digital information is created, accessed and preserved.

Design/methodology/approach

Written from the perspective of a digital collections librarian, this paper relies on existing research in presenting ethical considerations and complements that research with professional observations in providing subsequent reflections on addressing challenges in the age of digital information.

Findings

There are and should be considerations given to not only what information is contained in a given collection, but also how that information is selected, accessed and consumed by the public. The conclusions offered are designed to provoke reflection on the evolving and interconnected nature of information and ethics in the context of digital collections.

Originality/value

Information ethics is multifaceted, with one of those facets relating directly to digital collections. This paper demonstrates that digital collections are more complex than simply a collection of digitized documents and photographs. As the field of information management continually evolves and adapts, so, too, do the ethical realizations identified in this paper, all of which go beyond the (virtual) walls of a library, archive or museum, and carry the potential to have a long-term impact concerning information and its integrity, equity and access.
The synergistic effect of ego-network stability and whole network position: a perspective of transnational coopetition network
Authors: Feiyang Guan , Tienan Wang , Linbing Sun , Liqing Tang
Published: August 2021

Purpose

The authors selected global automobile manufacturing firms whose sales ranked within 100 in the five years from 2014 to 2018 in the Factiva database to examine how the characteristics of a firm's whole network and ego-network in a transnational coopetition network influence network performance.

Design/methodology/approach

The authors analyzed the public news of the sample firms about the coopetition by structural content analysis to build the coopetition networks and access to data on the competitive actions of firms. Then, to measure the variables associated with the coopetition network, such as the structural hole, centrality and ego-network stability, the authors use UCINET 6 that is a widely used piece of software for social network analysis to establishing five undirected binary adjacency matrices.

Findings

The authors find that a firm's competitive aggressiveness mediates the relationship between a firm's whole network position and network performance that emphasizes the need for integrating competitive dynamics research and coopetition research and shows how valuable insights can be gained through such integration. And the interaction of structural hole and centrality impacts competitive aggressiveness and network performance, and the interaction is different under high and low ego-network stability. The integration of whole network and ego-network literature studies provides new insights into firm network literature.

Practical implications

In the process of cooperation, firms should consider whether they can occupy the structural hole and center as important indicators for partner selection. Too stable relationship will prevent firms from obtaining new resources. Firms should weigh the period of cooperation according to specific situation.

Originality/value

These results indicate that ego-network stability, as an important complementary characteristic of coopetition network, has a significant synergistic effect with structural holes and centrality on competitive aggressiveness and network performance. And these findings expand the current literature on the relationship between characteristics of network, competitive aggressiveness and network performance.
Reconstructing ecological functions provided by extinct fauna using allometrically informed simulation models: An in silico framework for ‘movement palaeoecology’
Authors: Perry George L. W. , Wilmshurst Janet M. , Wood Jamie R.
Published: August 2021

Many ecological functions, including seed dispersal, pollination and the flow of nutrients between ecosystems, result from the movement of animals. The ongoing reduction and extinction of animal populations and species means that these functions are reduced or lost. As a result, conservation and restoration activities often seek to reinstate ecological functions to the communities from which they have been depleted.

Advances in movement and allometric ecology offer a way to reconstruct the movement and emergent functions of extinct taxa. Here, we describe a framework for integrating insights from movement ecology with allometric relationships linking body mass to movement and other traits and demonstrate how this can be used to reconstruct the emergent functions of extinct taxa. Allometric relationships are best resolved for vertebrates (especially mammals), so we highlight potential gaps relevant to developing trait‐based allometric movement models for data‐depauperate taxa.

To test our framework, we use it to estimate seed dispersal kernels for seven extant bird species for which seed dispersal distances are available. We then apply it to predict the movement activity and emergent seed dispersal kernels for three extinct endemic New Zealand bird species (two flightless and one volant), spanning four orders of magnitude in body mass.

The model performs satisfactorily for the extant species, with predicted mean, median and maximum seed dispersal distances overlapping empirical estimates, but with a tendency to over‐prediction. If empirical data were available, the model could be calibrated for specific taxa or landscapes. The model shows that the three extinct bird species could have been important agents of long‐distance seed dispersal, and comparable functions are probably now absent in New Zealand's ecosystems.

Summary. Trait‐based allometric models can be used to simulate the movement and associated functions of extinct animals. Reconstructing the functions of extinct (or data depauperate) species cannot be achieved by chaining together statistical relationships; such efforts must adequately represent natural history and carefully use computational model evaluation tools. A further challenge is adequately representing the effects of past landscape heterogeneity on disperser movement, fruit distribution and hence dispersal distances.

A free Plain Language Summary can be found within the Supporting Information of this article.
Extreme flood disturbance effects on multiple dimensions of river invertebrate community stability
Authors: Eagle Lawrence J. B. , Milner Alexander M. , Klaar Megan J. , Carrivick Jonathan L. , Wilkes Martin , Brown Lee E.
Published: August 2021

Multidimensional analysis of community stability has recently emerged as an overarching approach to evaluating ecosystem response to disturbance. However, the approach has previously been applied only in experimental and modelling studies.

We applied this concept to an 18‐year time series (2000–2017) of macroinvertebrate community dynamics from a southeast Alaskan river to further develop and test the approach in relation to the effects of two extreme flood events occurring in 2005 (event 1) and 2014 (event 2).

Five components of stability were calculated for pairs of pre‐ or post‐event years. Individual components were tested for differences between pre‐ and post‐event time periods. Stability components’ pairwise correlations were assessed and ellipsoids of stability were developed for each time period and compared to a null model derived from the permuted dataset.

Only one stability component demonstrated a significant difference between time periods. In contrast, 80% of moderate and significant correlations between stability components were degraded post‐disturbance and significant changes to the form of stability ellipsoids were observed. Ellipsoids of stability for all periods after the initial disturbance (2005) were not different to the null model.

Our results illustrate that the dimensionality of stability approach can be applied to natural ecosystem time‐series data. The major increase in dimensionality of stability observed following disturbance potentially indicates significant shifts in the processes which drive stability following disturbance. This evidence improves our understanding of community response beyond what is possible through analysis of individual stability components.
ICOS+ follicular regulatory T cells are implicated in the pathogenesis of ulcerative colitis
Authors: Yao Li , Guo Jianyang , Gui Juan , Bai Feihu , Xin Ruijuan , Deng Yanhong , Wang Shaoxuan , Li Haitao
Published: August 2021

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with a rising incidence worldwide. The precise aetiology is unclear, but aberrant regulatory T cell (Treg) responses have been documented in active UC patients. Follicular regulatory T cell (Tfr) is a recently identified subset of Treg cells. In this study, the role of ICOS in Tfr cells, which is a costimulatory molecule shown to stabilize and promote Treg differentiation, was investigated in UC patients. We found that with increasing UC severity, the frequency of ICOS+CD4 T cells was increased, but the level of ICOS expression by ICOS+ CD4 T cells was decreased. ICOS+ cells were highly enriched in follicular regulatory T cells (Tfr), which is a subset of Treg cells characterized by CD25+CD127−CXCR5+Foxp3+ phenotype. Anti‐CD3, anti‐CD3/CD28, or anti‐CD3/ICOS had all significantly increased the expression of Foxp3 and IL‐10, and among the three stimulation methods, anti‐CD3/ICOS was most effective at enhancing Foxp3 and IL‐10 expression. Moreover, anti‐CD3/ICOS‐stimulated Tfr cells could suppress conventional T cell proliferation in an IL‐10‐dependent manner. Interestingly, anti‐CD3/ICOS stimulation was less effective in UC‐Mild and UC‐Active patients compared to that in healthy and UC‐Remission patients. In addition, UC patients presented impairment in ICOS upregulation following anti‐CD3 stimulation. Overall, these data indicated that ICOS+ Tfr cells were dysregulated in UC patients and the level of dysregulation was associated with the severity of UC, suggesting that ICOS+Tfr cells could serve as a biomarker of the progression of UC.
Factors affecting primary care implementation for older veterans with multimorbidity in Veterans Health Administration (VA)
Authors: Adjognon Omonyêlé L. , Shin Marlena H. , Steffen Melissa J. A. , Moye Jennifer , Solimeo Samantha , Sullivan Jennifer L.
Published: August 2021

Objective

To identify factors affecting implementation of Geriatric Patient‐Aligned Care Teams (GeriPACTs), a patient‐centered medical home model for older adults with complex care needs including multiple chronic conditions (MCC), designed to provide them with comprehensive, managed, and coordinated primary care.

Data Sources

Qualitative data were collected from key informants at eight Veterans Health Administration Medical Centers geographically spread across the United States.

Study Design

Guided by the Consolidated Framework for Implementation Research (CFIR), we collected prospective primary data through semi‐structured interviews with GeriPACT team members (e.g., physicians, nurses, social workers, pharmacists), leaders (e.g., executive leaders, middle managers), and other staff referring to the program.

Data Collection

We conducted in‐person, semi‐structured interviews with 134 key informants. Interviews were recorded with permission and professionally transcribed. Transcripts were coded in Nvivo 11. We used directed content analysis to identify key factors affecting GeriPACT implementation across sites.

Principal Findings

Five key factors affected GeriPACT implementation—five CFIR constructs within two CFIR domains. Within the intervention characteristics domain, two constructs emerged, namely, (1) the structure of the GeriPACT model and (2) design, quality, and packaging. Within the inner setting domain, we identified three constructs, namely, (1) available resources (e.g., staffing and space, and infrastructure and information technology), (2) leadership support and engagement, and (3) networks and communications including teamwork, communication, and coordination.

Conclusions

Older veterans with MCC have complex primary care needs requiring high levels of care management and coordination. Knowing what key factors affect GeriPACT implementation is critical. Study findings also contribute to the growing implementation science literature on applying CFIR to evaluate factors that affect program implementation, especially to aging research. Further studies on MCC‐focused specialty primary care will help facilitate patient‐centered care provision for older adults' complex health needs while also leveraging synergistic work across factors affecting implementation.
Validation of the Nottingham Hip Fracture Score (NHFS) for the prediction of 30‐day mortality in a Swedish cohort of hip fractures
Authors: Olsen Fredrik , Lundborg Fredrika , Kristiansson Johan , Hård af Segerstad Mathias , Ricksten Sven‐Erik , Nellgård Bengt
Published: August 2021

Background

Hip fracture is a common osteoporotic fracture with great morbidity and mortality. The utility of ASA classification is limited, as most patients are ≥ASA 3. A reliable predictor of mortality risk could support decision‐making. We aimed to evaluate Nottingham hip fracture score (NHFS) for the prediction of 30‐day mortality and then to recalibrate the formula converting NHFS to risk of 30‐day mortality.

Methods

All patients >60 years with surgically treated hip fracture surgery during 2015–16 were assessed. Data was extracted manually from routinely collected clinical data in registry and medical records. Discriminative performance of NHFS and ASA was assessed with C‐statistics. The conversion formula from NHFS to risk of 30‐day mortality was recalibrated using logistic binominal regression. Observed vs expected ratios of 30‐day mortality were compared with the 2012 NHFS‐formula and recalibration was performed in a split dataset.

Results

1864 patients were included, with 213 deaths within 30 days. C‐statistic were 0.64 for NHFS and 0.62 for ASA. Comparing expected values from the 2012‐revision with our observed deaths gave a ratio of 1.37. Relating predicted levels of 30‐day mortality based on 70% of our cohort vs. 30% test portion of our Swedish dataset gave a ratio of 0.97.

Discussion

NHFS underestimated mortality in our cohort and showed poor discrimination. Revision of the formula based on a split dataset improved calibration. We suggest NHFS to be routinely implemented to support clinical judgements, expand preoperative assessment and escalate intraoperative monitoring.
The antagonistic pleiotropy of insulin‐like growth factor 1
Authors: Zhang William B. , Ye Kenny , Barzilai Nir , Milman Sofiya
Published: August 2021

While insulin‐like growth factor‐1 (IGF‐1) is a well‐established modulator of aging and longevity in model organisms, its role in humans has been controversial. In this study, we used the UK Biobank (n = 440,185) to resolve previous ambiguities in the relationship between serum IGF‐1 levels and clinical disease. We examined prospective associations of serum IGF‐1 with mortality, dementia, vascular disease, diabetes, osteoporosis, and cancer, finding two generalized patterns: First, IGF‐1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy; younger individuals with high IGF‐1 are protected from disease, while older individuals with high IGF‐1 are at increased risk for incident disease or death. Second, the association between IGF‐1 and risk is generally U‐shaped, indicating that both high and low levels of IGF‐1 may be detrimental. With the exception of a more uniformly positive relationship between IGF‐1 and cancer, these effects were remarkably consistent across a wide range of conditions, providing evidence for a unifying pathway that determines risk for most age‐associated diseases. These data suggest that IGF‐1 signaling could be harmful in older adults, who may actually benefit from the attenuation of biological growth pathways.
MeCP2 prevents age‐associated cognitive decline via restoring synaptic plasticity in a senescence‐accelerated mouse model
Authors: Huang Jin‐Lan , Zhang Fan , Su Min , Li Jiaxin , Yi Wen , Hou Li‐Xiang , Yang Si‐Man , Liu Jin‐Yuan , Zhang Hao‐An , Ma Tengfei , Wu Deng‐Pan
Published: August 2021

Age‐related cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD), is associated with the deficits of synaptic plasticity. Therefore, exploring promising targets to enhance synaptic plasticity in neurodegenerative disorders is crucial. It has been demonstrated that methyl‐CpG binding protein 2 (MeCP2) plays a vital role in neuronal development and MeCP2 malfunction causes various neurodevelopmental disorders. However, the role of MeCP2 in neurodegenerative diseases has been less reported. In the study, we found that MeCP2 expression in the hippocampus was reduced in the hippocampus of senescence‐accelerated mice P8 (SAMP8) mice. Overexpression of hippocampal MeCP2 could elevate synaptic plasticity and cognitive function in SAMP8 mice, while knockdown of MeCP2 impaired synaptic plasticity and cognitive function in senescence accelerated‐resistant 1 (SAMR1) mice. MeCP2‐mediated regulation of synaptic plasticity may be associated with CREB1 pathway. These results suggest that MeCP2 plays a vital role in age‐related cognitive decline by regulating synaptic plasticity and indicate that MeCP2 may be promising targets for the treatment of age‐related cognitive decline in neurodegenerative diseases.
Emergency medicine research: 2030 strategic goals
Authors: Neumar Robert W. , Blomkalns Andra L. , Cairns Charles B. , D’Onofrio Gail , Kuppermann Nathan , Lewis Roger J. , Newgard Craig D. , O’Neil Brian J. , Rathlev Niels K. , Rothman Richard E. , Wright David W.
Published: August 2021

All academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 years ago, EM has struggled to fulfill its research mission. EM ranks last among clinical specialties in the percentage of medical school faculty who are National Institutes of Health (NIH)‐funded principal investigators (PIs; 1.7%) and the percentage of medical school departments with NIH‐funded PIs (33%). Although there has been a steady increase in the number of NIH‐funded projects and total NIH dollars, the slowing growth in the number of NIH‐funded PIs and lack of growth in the number of EM departments with NIH‐funded PIs is cause for concern. In response, the Association of Academic Chairs of Emergency Medicine (AACEM) Research Task Force proposes a set of 2030 strategic goals for the EM research enterprise that are based on sustaining historic growth rates in NIH funding. These goals have been endorsed by the AACEM Executive Committee and the boards of Society for Academic Emergency Medicine (SAEM), American College of Emergency Physicians (ACEP), and American Academy of Emergency Medicine (AAEM). The 2030 strategic goals include 200 NIH‐funded projects led by 150 EM PIs in at least 50 EM departments with over $100M in annual funding resulting in over 3% of EM faculty being NIH‐funded PIs. Achieving these goals will require a targeted series of focused strategies to increase the number of EM faculty who are competitive for NIH funding. This requires a coordinated, intentional effort with investments at the national, departmental, and individual levels. These efforts are ideally led by medical school department chairs, who can create the culture and provide the resources needed to be successful. The specialty of EM has the obligation to improve the health of the public and to fulfill its research mission.
Paternal alcohol exposure reduces acquisition of operant alcohol self‐administration and affects Bdnf DNA methylation in male and female offspring
Authors: Nieto Steven J. , Haile Colin N. , Quave Cana B. , Harding Mark J. , Nielsen David A. , Meisch Richard A. , Kosten Therese A.
Published: August 2021

Familial transmission of alcohol use disorder reflects genetic and environmental factors. Paternal alcohol exposure may affect rodent offspring via epigenetic modifications transmitted through the male germ line. While such exposure alters alcohol sensitivity in mouse offspring, no studies examined if it impacts the development of operant alcohol self‐administration in rats. We exposed male (sires) Wistar rats to chronic intermittent ethanol in vapour chambers (16 h/day; 5 days/week) or to air for 6 weeks. Eight weeks later, rats were mated with alcohol‐naive females. Adult alcohol‐ and control‐sired F1 offspring were assessed in acquisition of alcohol self‐administration in which increasing alcohol concentrations (2.5%, 5% and 10%, v/v) were delivered after one lever press (fixed ratio 1 or FR1). Prior to alcohol sessions, rats were trained to lever press for food delivery under an FR1 schedule of reinforcement. DNA methylation levels of the brain derived neurotrophic factor (Bdnf) gene were measured in sperm, nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) in sires and in offspring. Alcohol‐exposed sires had lower Bdnf DNA methylation levels in NAc and greater methylation levels in mPFC. Although this pattern was not recapitulated in offspring, alcohol‐sired offspring of both sexes did show aberrant Bdnf DNA methylation patterns compared to control‐sired offspring. Alcohol‐sired offspring self‐administered less alcohol (5% and 10%) with no group differences in food responding. Results indicate that paternal alcohol exposure prior to conception protects against alcohol's initial reinforcing effects but the pattern of dysregulated Bdnf methylation in reward‐related circuitry did not mimic changes seen in sires.