bluuebunny/crossref_metadata_2025 huggingface dataset:
Oil body formation inMarchantia polymorphais controlled by MpC1HDZ and serves as a defense against arthropod herbivores
Authors: Romani Facundo , Banic Elizabeta , Florent Stevie N. , Kanazawa Takehiko , Goodger Jason Q.D. , Mentink Remco , Dierschke Tom , Zachgo Sabine , Ueda Takashi , Bowman John L. , Tsiantis Miltos , Moreno Javier E.
Published: March 2020

The origin of a terrestrial flora in the Ordovician required adaptation to novel biotic and abiotic stressors. Oil bodies, a synapomorphy of liverworts, accumulate secondary metabolites, but their function and development are poorly understood. Oil bodies ofMarchantia polymorphadevelop within specialized cells as one single large organelle. Here, we show that a CLASS I HOMEODOMAIN LEUCINE-ZIPPER (C1HDZ) transcription factor controls the differentiation of oil body cells in two different ecotypes of the liverwortM. polymorpha, a model genetic system for early divergent land plants. In flowering plants, these transcription factors primarily modulate responses to abiotic stresss including drought. However, loss-of-function alleles of the single ortholog gene, MpC1HDZ, inM. polymorphadid not exhibit phenotypes associated with abiotic stress. Rather Mpc1hdzmutant plants were more susceptible to herbivory and total plant extracts of the mutant exhibited reduced antibacterial activity. Transcriptomic analysis of the mutant revealed a reduction in expression of genes related to secondary metabolism that was accompanied by a specific depletion of oil body terpenoid compounds. Through time lapse imaging we observed that MpC1HDZ expression maxima precede oil body formation indicating that MpC1HDZ mediates differentiation of oil body cells. Our results indicate thatM. polymorphaoil bodies, and MpC1HDZ, are critical for defense against herbivory but not for abiotic stress-tolerance. Thus, C1HDZ genes were co-opted to regulate separate responses to biotic and abiotic stressors in two distinct land plant lineages.
MiRNA and phasiRNAs-mediated regulation of TIR-NBS-LRR defense genes inArabidopsis thaliana
Authors: López-Márquez Diego , Del-Espino Ángel , López-Pagán Nieves , Rodríguez-Negrete Edgar A. , Rubio-Somoza Ignacio , Ruiz-Albert Javier , Bejarano Eduardo R. , Beuzón Carmen R.
Published: March 2020

Plants encode large numbers of intracellular immune receptors known as resistance (R) proteins or nucleotide-binding (NB) leucine-rich repeat (LRR) receptors (NLRs), involved in perception of pathogen-derived effectors and activation of immunity.

Here, we report a two-tiered regulatory network mediated by microRNA and secondary phased small RNAs (phasiRNA) that targets the silencing of dozens of NLR genes encoding yet uncharacterized members of the Toll/interleukin-1 (TIR)-NBS-LRR (TNLs) subfamily inArabidopsis. We show that miR825-5p downregulates expression ofArabidopsis AT5G38850gene (renamed asmicroRNA-silenced TNL 1 or MIST1) by targeting the sequence coding for a highly conserved functional amino acid motif (TIR2) within the TIR domain of the receptor. Further, we show thatMIST1functions as a regulatory hub, since miRNA825-5p triggers RDR6-mediated processing ofMIST1transcripts, to generatetrans-acting phasiRNAs that in turn target, a wide network of TNL genes for gene silencing. Regulation throughMIST1affects disease resistance against the model bacterial pathogenPseudomonas syringae, since altered levels of miRNA825-5p lead to changes inArabidopsisability to establish basal defenses against this pathogen. MiR825-5p is expressed in unchallenged adult leaves and its production is down regulated in response to PAMPs such as bacterial flagellin but also fungal chitin.
A Computational Model of Stem Cell Molecular Mechanism to Maintain Tissue Homeostasis
Authors: Khorasani Najme , Sadeghi Mehdi , Nowzari-Dalini Abbas
Published: March 2020

Stem cells, with their capacity to self-renew and to differentiate to more specialized cell types, play a key role to maintain homeostasis in adult tissues. To investigate how, in the dynamic stochastic environment of a tissue, non-genetic diversity and the precise balance between proliferation and differentiation are achieved, it is necessary to understand the molecular mechanisms of the stem cells in decision making process. By focusing on the impact of stochasticity, we proposed a computational model describing the regulatory circuitry as a tri-stable dynamical system to reveal the mechanism which orchestrate this balance. Our model explains how the distribution of noise in genes, linked to the cell regulatory networks, controls cell decision-making to maintain homeostatic state. The noise control over tissue homeostasis is achieved by regulating the probability of differentiation and self-renewal through symmetric and/or asymmetric cell divisions. Our model reveals, when mutations due to the replication of DNA in stem cell division, are inevitable, how mutations contribute to either aging gradually or the development of cancer in a short period of time. Furthermore, our model sheds some light on the impact of more complex regulatory networks on the system robustness against perturbations.
Ageing compromises mouse thymus function and remodels epithelial cell differentiation
Authors: Baran-Gale J , Morgan MD , Maio S , Dhalla F , Calvo-Asensio I , Deadman ME , Handel AE , Maynard A , Chen S , Green F , Sit RV , Neff NF , Darmanis S , Tan W , May AP , Marioni JC , Ponting CP , Holländer GA
Published: March 2020

Ageing is characterised by cellular senescence, leading to imbalanced tissue maintenance, cell death and compromised organ function. This is first observed in the thymus, the primary lymphoid organ that generates and selects T cells. However, the molecular and cellular mechanisms underpinning these ageing processes remain unclear. Here, we show that mouse ageing leads to less efficient T cell selection, decreased self-antigen representation and increased T cell receptor repertoire diversity. Using a combination of single-cell RNA-seq and lineage-tracing, we find that progenitor cells are the principal targets of ageing, whereas the function of mature thymic epithelial cells is compromised only modestly. Specifically, an early-life precursor cell population, retained in the mouse cortex postnatally, is virtually extinguished at puberty. Concomitantly, a medullary precursor cell quiesces, thereby impairing maintenance of the medullary epithelium. Thus, ageing disrupts thymic progenitor differentiation and impairs the core immunological functions of the thymus.
Mechanosensitive activation of mTORC1 mediates ventilator induced lung injury during the acute respiratory distress syndrome
Authors: Lee Hyunwook , Fei Qinqin , Streicher Adam , Zhang Wenjuan , Isabelle Colleen , Patel Pragi , Lam Hilaire C. , Pinilla-Vera Miguel , Amador-Munoz Diana , Barragan-Bradford Diana , Higuera Angelica , Putman Rachel K. , Henske Elizabeth P. , Bobba Christopher M. , Higuita-Castro Natalia , Hite R. Duncan , Christman John W. , Ghadiali Samir N. , Baron Rebecca M. , Englert Joshua A.
Published: March 2020

Acute respiratory distress syndrome (ARDS) is a highly lethal condition that impairs lung function and causes respiratory failure. Mechanical ventilation maintains gas exchange in patients with ARDS, but exposes lung cells to physical forces that exacerbate lung injury. Our data demonstrate that mTOR complex 1 (mTORC1) is a mechanosensor in lung epithelial cells and that activation of this pathway during mechanical ventilation exacerbates lung injury. We found that mTORC1 is activated in lung epithelial cells following volutrauma and atelectrauma in mice and humanized in vitro models of the lung microenvironment. mTORC1 is also activated in lung tissue of mechanically ventilated patients with ARDS. Deletion ofTsc2, a negative regulator of mTORC1, in epithelial cells exacerbates physiologic lung dysfunction during mechanical ventilation. Conversely, treatment with rapamycin at the time mechanical ventilation is initiated prevents physiologic lung injury (i.e. decreased compliance) without altering lung inflammation or barrier permeability. mTORC1 inhibition mitigates physiologic lung injury by preventing surfactant dysfunction during mechanical ventilation. Our data demonstrate that in contrast to canonical mTORC1 activation under favorable growth conditions, activation of mTORC1 during mechanical ventilation exacerbates lung injury and inhibition of this pathway may be a novel therapeutic target to mitigate ventilator induced lung injury during ARDS.
Response patterns and mechanisms of plants to water stress
Authors: Sun Yuan , Wang Cuiting , Chen Han Y.H. , Ruan Honghua
Published: March 2020

Plants are key to the functionality of many ecosystem processes. The duration and intensity of water stress are anticipated to increase in the future; however, an elucidation of the responses of plants to water stress remains incomplete. For this study, we present a global meta-analysis derived from 1301 paired observations from 84 studies to evaluate the response patterns and mechanisms of plants to water stress. The results revealed that while water stress inhibited plant growth and photosynthesis, reactive oxygen species (ROS), plasma membrane permeability, enzymatic antioxidants, and non-enzymatic antioxidants increased. These responses generally increased with the intensity of water stress but were mitigated with experimental duration. Our findings suggested that the overproduction of ROS was the primary mechanism of plants in response to water stress and that plants tend to acclimate to water stress over time to some extent. Our synthesis provides a framework for understanding the responses and mechanisms of plants under drought conditions.

One senence summary

The overproduction of ROS was the primary mechanism of plants in response to water stress and that plants tend to acclimate to water stress over time to some extent.
An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis
Authors: Xiang Guanjue , Keller Cheryl A. , Heuston Elisabeth , Giardine Belinda M. , An Lin , Wixom Alexander Q. , Miller Amber , Cockburn April , Sauria Michael E.G. , Weaver Kathryn , Lichtenberg Jens , Göttgens Berthold , Li Qunhua , Bodine David , Mahony Shaun , Taylor James , Blobel Gerd A. , Weiss Mitchell J. , Cheng Yong , Yue Feng , Hughes Jim , Higgs Douglas R. , Zhang Yu , Hardison Ross C.
Published: March 2020

Thousands of epigenomic data sets have been generated in the past decade, but it is difficult for researchers to effectively use all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for validated systematic integration of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic features and transcriptomes from many sources, including individual laboratories and consortia, to produce a comprehensive view of the regulatory landscape of differentiating hematopoietic cell types in mouse. By using IDEAS as our integrative and discriminative epigenome annotation system, we identified and assigned epigenetic states simultaneously along chromosomes and across cell types, precisely and comprehensively. Combining nuclease accessibility and epigenetic states produced a set of more than 200,000 candidate cis-regulatory elements (cCREs) that efficiently capture enhancers and promoters. The transitions in epigenetic states of these cCREs across cell types provided insights into mechanisms of regulation, including decreases in numbers of active cCREs during differentiation of most lineages, transitions from poised to active or inactive states, and shifts in nuclease accessibility of CTCF-bound elements. Regression modeling of epigenetic states at cCREs and gene expression produced a versatile resource to improve selection of cCREs potentially regulating target genes. These resources are available from our VISION website to aid research in genomics and hematopoiesis.
Embracing evaluation theory to overcome “stasis”
Authors: Macnamara Jim
Published: March 2020

Purpose

This paper aims to explore the evaluation theory in a field closely related to corporate communication and public relations (PR) as well as in other disciplines and argues that embracing the evaluation theory more broadly can break the “stasis” and “deadlock” identified in evaluation of corporate communication and PR. Specifically, this analysis seeks to show that a transdisciplinary approach can contribute to standards and demonstration of impact – two long-sought goals in evaluation of corporate communication and PR – as well as inform methodology.

Design/methodology/approach

Critical analysis is applied to review the evaluation theory in a number of fields, including international development, public administration, management and health communication, compared with major frameworks, models and methods used for evaluation of corporate communication and PR.

Findings

This analysis shows that the evaluation theory in other fields and related theory of change, program theory and program logic models can contribute to advancing evaluation of corporate communication and PR in three ways: identifying standards in terminology and approaches, shifting focus from activities and outputs to outcomes and impact and applying appropriate and rigorous methodology.

Research limitations/implications

While this paper does not present new empirical data, it expands the theoretical perspectives, models and methods applied to the evaluation of corporate communication and PR and identifies new directions for research.

Originality

As well as expanding the evaluation theory and opening up new ground for research, this analysis identifies a need for structural change in the field of practice.
The correlations between livelihood capitals and perceived recovery
Authors: Han Ziqiang , Wang Lei , Wei Jianwen
Published: March 2020

Purpose

This study examines the recovery of households after disasters from the sustainable livelihood approach (SLA) perspective.

Design/methodology/approach

This study analyzes the perception of recovery by using a longitudinal household survey data set collected from a Chinese county devastated by the 2008 Wenchuan earthquake. The analysis compares the changes of livelihood capitals (financial, natural, physical, social, human) between 2012 and 2009 and recovery perception.

Findings

The results demonstrate that both the current status of financial, natural, and social capital and the changes of the capitals between 2009 and 2012 are positively correlated with the perceived level of recovery. The associations between the current status and the change of physical capital and recovery perception are insignificant. In contrast, with a greater change of human capital between 2009 and 2012, participants have a lower perception of recovery.

Originality/value

By investigating a longitudinal data, this study indicates that (1) household recovery should be considered as multidimensional, (2) the SLA could be a feasible framework to measure recovery, and (3) individual's recovery perception is dependent on the various dimensions of recovery measures.
Brand orientation, brand-building behavior and brand identity in SMEs: an empirical evaluation
Authors: Osakwe Christian Nedu , Palamidovska-Sterjadovska Nikolina , Mihajlov Martin , Ciunova-Shuleska Anita
Published: March 2020

Purpose

This study aims to facilitate the understanding of brand building among owners/managers of SMEs by highlighting the relationships among the multidimensionality of brand orientation, brand-building behavior and brand identity.

Design/methodology/approach

In addressing the research issue, the study uses responses from 158 domesticated SMEs in North Macedonia, afterwards relying on structural equation modeling to test the research propositions.

Findings

This study validates brand orientation as a multidimensional term that is underlined by brand artefacts, norms and values. This study also validates the assumptions that brand orientation, brand-building behavior and brand identity are significantly related.

Research limitations/implications

While it is possible that our evidence base is limited to the context studied, the research findings nevertheless contribute primarily to the emergent scholarship on SMEs' brand building.

Practical implications

This study has practical consequences for SMEs' brand building. More specifically, it enriches the understanding of the interrelationships between brand orientation, brand-building behavior and brand identity.

Originality/value

This study provides an advanced perspective of brand orientation as a complex phenomenon and further provides understanding of its relations to brand-building behavior and brand identity of the domesticated SMEs.
Magnetohydrodynamic flow of Carreau liquid over a stretchable sheet with a variable thickness
Authors: Mahanthesh B.
Published: March 2020

Purpose

The magnetohydrodynamic (MHD) flow problems are important in the field of biomedical applications such as magnetic resonance imaging, inductive heat treatment of tumours, MHD-derived biomedical sensors, micropumps for drug delivery, MHD micromixers, magnetorelaxometry and actuators. Therefore, there is the impact of the magnetic field on the transport of non-Newtonian Carreau fluid in the presence of binary chemical reaction and activation energy over an extendable surface having a variable thickness. The significance of irregular heat source/sink and cross-diffusion effects is also explored.

Design/methodology/approach

The leading governing equations are constructed by retaining the effects of binary chemical reaction and activation energy. Suitable similarity transformations are used to transform the governing partial differential equations into ordinary differential equations. Subsequent nonlinear two-point boundary value problem is treated numerically by using the shooting method based on Runge–Kutta–Fehlberg. Graphical results are presented to analyze the behaviour of effective parameters involved in the problem. The numerical values of the mass transfer rate (Sherwood number) and heat transfer rate (Nusselt number) are also calculated. Furthermore, the slope of the linear regression line through the data points is determined in order to quantify the outcome.

Findings

It is established that the external magnetic field restricts the flow strongly and serves as a potential control mechanism. It can be concluded that an applied magnetic field will play a major role in applications like micropumps, actuators and biomedical sensors. The heat transfer rate is enhanced due to Arrhenius activation energy mechanism. The boundary layer thickness is suppressed by strengthening the thickness of the sheet, resulting in higher values of Nusselt and Sherwood numbers.

Originality/value

The effects of magnetic field, binary chemical reaction and activation energy on heat and mass transfer of non-Newtonian Carreau liquid over an extendable surface with variable thickness are investigated for the first time.
Shared leadership and team creativity
Authors: Lyndon Shiji , Pandey Ashish , Navare Ajinkya
Published: March 2020

Purpose

The purpose of this paper is to extend the theoretical understanding and conceptualization of shared leadership by examining the impact of cognitive trust as an antecedent of shared leadership. Further, the study examines the mediating effect of team learning on relationship between shared leadership and team creativity.

Design/methodology/approach

The study adopted a mixed method approach with sequential explanatory research strategy. Using a survey questionnaire, data from 44 teams were collected at two different time points. Semistructured interviews were carried out with 22 teams to explain the results that emerged from the quantitative study.

Findings

The study found that cognitive trust positively influences shared leadership. Further, team learning fully mediates the relationship between shared leadership and team creativity. The major themes that emerged from the qualitative study are participant's experiences of shared leadership in team, reasons to exert leadership, reasons to accept leadership and consequences of shared leadership.

Practical implications

Organizations can enhance team creativity by promoting shared leadership in the organization.

Originality/value

This study examines the mediating process of team learning between shared leadership and team creativity. Mixed method approach adopted in the study explains the shared leadership process by building on both quantitative and qualitative research.
Exploiting online environment to engage customers: social commerce brand community
Authors: Cuomo Maria Teresa , Mazzucchelli Alice , Chierici Roberto , Ceruti Francesca
Published: March 2020

Purpose

Taking jointly into account social commerce and online brand community, this paper aims to investigate how the growth of social commerce and the fast adoption of online brand communities have given firms the opportunity to establish a new kind of community, namely, the social commerce brand community. Adopting a managerial perspective, the research aims to identify the core dimensions of social commerce brand community and shed light on how they contribute in engaging customers and transform them into brand advocates.

Design/methodology/approach

Five social commerce retailers operating into five different sectors of activity have been involved in a multiple case study. Data retrieved from semi-structured interviews have been triangulated with information gathered from different sources to provide depth to the cases and enhance data validity.

Findings

This study substantiates the rise of social commerce brand community as a new phenomenon that differs from traditional online brand communities and provides firms with concrete support in selling activities and in managing relationships with customers. The multiple case study allows also to detect social commerce brand community core pillars, namely, participants’ identification, participation, conversation and social support. These four elements turned out to be crucial to develop an effective social commerce brand community.

Research limitations/implications

This study extends existing theory on social commerce and online brand community by investigating the social commerce brand community as a new phenomenon and clarifying the fundamental pillars on which it relies.

Originality/value

This study extends existing theory on social commerce and online brand community by investigating the social commerce brand community as a new phenomenon and clarifying the fundamental pillars on which it relies.
Development aid and the governance of global value chains the case of the Bangladesh accord on fire and building safety
Authors: Beierlein Laurence
Published: March 2020

Purpose

The purpose of this paper is to investigate the relevance and contradictions of development aid in crafting governance responses for enabling long term social upgrading in global garment value chains. Since governance responses are multilevel, we propose to analyse the interrelation between the global and the local level through the case study of a private regulatory initiative of a new type: the Accord on Fire and Building Security in Bangladesh, operationally run like a development aid programme. We aim at explaining the reasons why it has been banned from operating in the country.

Design/methodology/approach

We use the framework of the Global Value Chain (GVC) approach since it is operationally used in development aid and has broadened its focus to investigating the link between economic and social upgrading. It further helps to understand multilevel and multiactor governance responses. Using multiple secondary sources we describe the context in which the Accord emerged, explore its provisions and operations, and analyse the contestation pertaining to its termination. We analyse the Accord both as a global governance tool and a field-level development aid actor that addresses social issues in GVCs.

Findings

As an ILO led operational programme, the Accord, since its inception, has proven globally effective at improving workplace safety for many workers. However it has been resented for being hegemonic and, as a governance tool, it has neither succeeded in addressing the flaws of private regulatory initiatives nor changed existing power relationships in GVCs.

Originality/value

The early termination of the Accord has not yet been analysed. In light of this, we propose new insights on the rising role of development aid in private governance responses.
Random sampling in metagenomic sequencing leads to overestimated spatial scaling of microbial diversity
Authors: Tu Qichao
Published: March 2020

Revealing the spatial scaling patterns of microbial diversity is of special interest in microbial ecology. One critical question is whether the observed spatial turnover rate truly reflect the actual spatial patterns of extremely diverse microbial communities. Using simulated mock communities, this study suggested that the currently observed microbial spatial turnover rates were overestimated by random sampling processes associated with high‐throughput metagenomic sequencing. The observed z values were largely contributed by accumulated microbial taxa due to cumulative number of samples. This is a crucial issue because microbial communities already have very low spatial turnover rate due to the small size and potential cosmopolitism nature of microorganisms. Further investigations suggested a linear relationship between the observed and expected z values, which can be applied to remove random sampling noises from the observed z values. Adjustment of z values for data sets from six American forests showed much lower spatial turnover rate than that before adjustment. However, the patterns of z values among these six forests remained unchanged. This study suggested that our current understanding of microbial taxa–area relationships could be inaccurate. Therefore, cautions and efforts should be made for more accurate estimation and interpretation of microbial spatial patterns.
(Non)Urban Humans: Questions for a Research Agenda (the Work the Urban Could Do)
Authors: Simone Abdoumaliq
Published: March 2020

This interventions essay deploys the notion of the (non)urban human to address the conundrums associated with identifying spaces, operations and entities outside of urbanization's planetary encompassment. In the piece, the objective of which is to call for a programme of prospective research collaborations, it seeks to explore domains of intersection among that which appears ‘left out’ of urbanization's purported advantages, that whose time has yet to come, and forms of the human that exceed the possibilities of self‐reflexive consciousness and free will. The essay draws upon the temporalities, rhythms, spatial arrangements and sensoria generated through histories of blackness and ‘natural worlds’ and their interactions, to posit extensionality—a dispersal of bodies and their capacities into more reciprocal and mutual enactments with the earthly surrounds—as a generative by‐product of extended urbanization.
Physicochemical properties and organoleptic aspects of ice cream enriched with microencapsulated pistachio peel extract
Authors: Ghandehari Yazdi Amir Pouya , Barzegar Mohsen , Ahmadi Gavlighi Hassan , Sahari Mohammad Ali , Mohammadian Amir Hoseein
Published: March 2020

The purpose of this study was to produce a functional ice cream by the addition of microcapsules of pistachio peel extract (MPPE). Various properties of the resulting ice cream were investigated. By increasing the amount of MPPE the total phenolic content and antioxidant activity increased about 2.0‐ and 3.7‐fold, respectively, compared with the control sample. The rheological properties of the mixes were fitted by the Power Law model. All mixes showed non‐Newtonian pseudoplastic behaviour. By increasing the concentration of MPPE, the consistency coefficient (m), viscosity, and shear sensitivity were increased, but the flow behaviour index (n) decreased. The addition of MPPE to ice cream mixes improved the melting resistance, first dripping times and functional properties of ice cream such as antioxidant activity and total phenolic content. The results of the sensory analysis showed that the addition of MPPE had no significant effect on the overall acceptability of the product. Based on our findings, MPPE has the potential to be used as an added‐value ingredient in the ice cream industry to enhance the functional properties of their products.
Volatile organic compound profiles of yoghurt produced from cow's milk with different somatic cell counts
Authors: Ivanov Galin , Bilgucu Ertugrul , Ivanova Ivelina , Dimitrova Milena
Published: March 2020

The present study aimed to investigate the effect of somatic cell count (SCC) of raw cow's milk on the volatile organic compound (VOC) profiles of yoghurt. Test yoghurt samples were produced from three batches of cow's milk with low, medium and high SCC, respectively. The VOCs were determined by gas chromatography–mass spectrometry (GC–MS) analysis. A lower diacetyl and acetoin content and a higher content of 2‐heptanone, and butanoic and hexanoic acids were established in the yoghurt samples from batches with high SCC of above 1 000 000 cells/cm3. The increased SCC of cow's milk had a negative effect on the volatile organic compound profiles of yoghurt.
Adverse pregnancy outcomes and subsequent development of connective tissue disease in the UK: an epidemiological study
Authors: Kither H , Heazell A , Bruce IN , Tower C , Crocker I
Published: March 2020

Objective

This study assessed prevalence of connective tissue disease (CTDs), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) in women with previous adverse pregnancy outcome compared with uncomplicated livebirths.

Design

Retrospective case–control study.

Setting

UK Primary Care.

Population or sample

Records of women, 18 years and older, within the Clinical Practice Research Datalink (CPRD) (1 January 2000–31 December 2013).

Methods

Clinical Practice Research Datalink was searched for pregnancy terms to identify adverse pregnancy outcome. Each identified case was matched to five livebirths.

Main outcome measures

Diagnosis of SLE, CTD, APS or autoimmune antibodies. Poisson regression was performed to calculate relative risk ratios (RR), comparing adverse pregnancy outcome with livebirth cohorts.

Results

Clinical Practice Research Datalink identified 20 123 adverse pregnancy outcomes matched to 97 323 livebirths, with a total of 875 590 person‐years follow up. Median follow up from study entry was 7.29 years (SD 4.39). Compared with women with an uncomplicated livebirth, women with adverse pregnancy outcome had an increased risk of developing CTD or autoimmune antibodies (RR 3.20, 95% CI 2.90–3.51). Risk was greatest following a stillbirth (RR 5.82, 95% CI 4.97–6.81). For CTD and SLE, the risk was greatest within the first 5 years of adverse pregnancy outcome. Risk for aPL and APS diagnosis was highest ≥5 years from adverse pregnancy outcome.

Conclusions

Adverse pregnancy outcome is associated with increased risk of developing maternal CTD, including SLE. Either immunological factors predispose women to adverse pregnancy outcome and subsequent CTD diagnosis or, alternatively, adverse pregnancy outcome initiates autoimmune events which culminate in CTD in later life.

Tweetable abstract

Stillbirth is associated with increased maternal risk of developing systemic lupus erythematosus (SLE).
Paper Versus Practice: A Field Investigation of Integrity Hotlines
Authors: SOLTES EUGENE
Published: March 2020

In an effort to motivate firms to more rapidly detect potential misconduct, legislators, regulators, and enforcement agencies incentivize firms to have integrity or “whistleblowing” hotlines. These hotlines provide individuals an opportunity to report alleged misconduct and seek guidance about how to appropriately respond. Beyond some isolated examples, little is known about the responsiveness of hotlines to actual claims of alleged misconduct. I undertake a field study to investigate how hotlines function in practice by making four different inquiries involving alleged misconduct to nearly 250 firms. I find that one‐fifth of firms have impediments (e.g., phone line disconnected, email bounce back, direct to incorrect website) that hinder reporting and approximately 10% of firms do not respond in a timely manner. Overall, this investigation illuminates several differences between integrity hotlines “on paper” and how they actually perform in practice.
Mucosectomy device‐assisted endoscopic resection of gastric subepithelial lesions
Authors: Li Lian Yong , Li Bai Wen , Mekaroonkamol Parit , Chen Hui Min , Shen Shan Shan , Luo Hui , Dacha Sunil , Xue Yue , Cristofaro Sarah , Keilin Steven , Willingham Field , Cai Qiang
Published: March 2020

Objective

Some gastrointestinal subepithelial tumors (SETs) have malignant potential and complete resection may be required. However, endoscopic submucosal dissection (ESD) can be a tedious procedure and requires a long and extensive training to master. Devices for endoscopic full‐thickness resection (EFTR) are limited and are not widely available. We report here a simpler endoscopic method to resect small SETs using a commercially available endoscopic mucosal resection (EMR) kit and enucleation technique.

Methods

All patients with SET who underwent device‐assisted resection at our tertiary care hospital from April 2015 to November 2016 were enrolled in this retrospective study. All procedures were performed by a single expert endoscopist with an advanced endoscopy trainee. A mucosectomy and a limited dissection under mucosa were performed to preserve the mucosa before a device‐assisted enucleation of the tumor to facilitate endoscopic closure of the defect closure in all cases.

Results

A total of 12 patients aged 38–70 y, of whom six were males, were included. Most of the tumors originated from the muscularis propria and were located at the proximal gastric body. The mean procedural duration was 53 minutes (range 23‐91 min). The average size of the lesions was 13 mm (range 9–21 mm). The mean duration of hospitalization was 1.3 days. Bleeding and intentional perforation were all successfully managed during the procedure and did not result in any clinically significant adverse event.

Conclusion

A device‐assisted EFTR using a commercially available EMR kit is a safe and feasible method for the endoscopic resection of small gastric extrovert SETs.
Trend analysis of lung cancer mortality and years of life lost (YLL) rate from 1999 to 2016 in Tianjin, China: Does the lung cancer burden in rural areas exceed that of urban areas?
Authors: Zheng Wenlong , Zhang Hui , Shen Chengfeng , Zhang Shuang , Wang Dezheng , Li Wei , Jiang Guohong
Published: March 2020

Background

The aim of this study was to examine the trends in the mortality rate and years of life lost (YLL) rate of lung cancer in Tianjin, China, during the period from 1999 to 2016.

Methods

Lung cancer death data were obtained from Tianjin residents' all‐cause death monitoring system, which covers the whole population of Tianjin. Crude mortality rate, age‐standardized mortality rate, truncated rate (35–64 years), YLL and age‐standardized YLL rate data were calculated and trends examined.

Results

From 1999 to 2016, a total of 93 358 lung cancer deaths were reported in Tianjin, which accounted for 38.0% of all cancer deaths (93 358/245744). The crude mortality rate of lung cancer had increased 58.5% from 1999 (40.15/100000) to 2016 (63.64/100000), average annual percent change (AACP) = 2.9%, P < 0.01. However, the age‐standard YLL rate had decreased to 13.3% in 2016 than in 1999, AACP = –0.8%, P < 0.01, with a stable trend in males (AACP = –0.2%), and noticeable decreasing trend in females (AACP = –1.4%). The lung cancer mortality rate (ASRW) in urban areas was higher than that in rural areas in 1999, with a ratio of 1.99:1. However, it was lower in 2016, with the ratio of 0.98:1. For the truncated rate (35–64 years), it had decreased in urban areas compared with rural areas since the year 2013.

Conclusion

Lung cancer remains the most fatal cancer in Tianjin. However, the age‐standard YLL rate of lung cancer has decreased considerably accompanied by a decline in smoking rate years ago, especially in women and people living in urban areas. Considerable attention is therefore needed in the rural areas where cases of lung cancer are still rapidly increasing.
Patterns of response in metastatic NSCLC during PD‐1 or PD‐L1 inhibitor therapy: Comparison of the RECIST 1.1 and iRECIST criteria
Authors: Liang Hongge , Xu Yan , Chen Minjiang , Zhong Wei , Wang Mengzhao , Zhao Jing
Published: March 2020

Background

Immunotherapy plays an important role in advanced non‐small cell lung cancer (NSCLC). However, radiological evaluation is challenging due to the potential inflammatory effects of immunotherapy, which can lead to atypical response patterns. Identifying these atypical responses is critical to making treatment decisions and prognostication.

Methods

We performed a retrospective analysis of consecutive advanced NSCLC patients treated with immunotherapy (alone or in combination). We collected patients' clinical and pathological data, analyzed the proportion of patients who continued immunotherapy beyond progressive disease (PD) per RECIST 1.1, and compared the differences in response patterns between the RECIST 1.1 and iRECIST criteria.

Results

A total of 43 patients treated at the Peking Union Medical College, China from January 2018 to April 2019 were included. Continued immunotherapy beyond PD per RECIST 1.1 was observed in 10 (33.3%, 10/30) patients, of which there were discordant assessments (30%, 3/10) between the RECIST 1.1 and iRECIST, which were evaluated as PD by RECIST 1.1 and immune unconfirmed PD by iRECIST. Among seven patients with immune confirmed PD, one (1/30, 3.3%) had pseudoprogression. Patients who continued immunotherapy beyond PD (n = 10) experienced significantly prolonged overall survival (not reached vs. 8.1 months: hazard ratio, 2.8; 95% confidence interval: 2.7–13.6, P = 0.03) compared with patients who did not continue immunotherapy beyond PD (n = 20).

Conclusions

RECIST 1.1 evaluation underestimated the benefit of immunotherapy. Further research is required to optimize iRECIST and establish some criteria for selecting patients who will benefit from continued immunotherapy beyond PD per RECIST 1.1.
The effect of four materials on direct pulp capping: An animal study
Authors: Zaen El‐Din Ahmed M. , Hamama Hamdi H. , Abo El‐Elaa Mohammed A. , Grawish Mohammed E. , Mahmoud Salah H. , Neelakantan Prasanna
Published: March 2020

The aim of this study was to investigate the outcomes of direct pulp capping performed with two types of tricalcium silicate‐based materials (mineral trioxide aggregate/MTA and Biodentine/BD); nano‐hydroxyapatite (nHAP) crystals or calcium hydroxide (CH) in dogs. Following mechanical exposure, the pulps were randomly capped with one of the four materials. Histological analyses were performed to examine the outcomes after 7 days or 3 months. At 7 days, BD and nHAP showed significantly less inflammatory cell response than MTA and CH. At 3 months, the inflammatory cell response and tissue necrosis were significantly higher in the CH group. There was no significant difference between the tested materials in the calcific bridge formation after 7 days; however, a significant difference was noticed at the 3‐month period. Tricalcium silicate‐based cements and nHAP are potential alternatives to CH in vital pulp therapy following accidental pulp exposure.
Colorectal cancer in the United States and a review of its heterogeneity among Asian American subgroups
Authors: Gu Mofan , Thapa Susan
Published: March 2020

Colorectal cancer is the third most common cancer in the United States. Established risk factors include older age, unhealthy lifestyle (high consumptions of red/preserved meat, low consumptions of fruit and vegetables, smoking, high alcohol consumption, and lack of physical activities), personal and family medical histories and low socioeconomic status (low insurance coverage, education and income). Asian American subgroups vary significantly in terms of culture, socioeconomic status, and health behaviors, yet most registries and researches aggregate all Asian Americans as one group. In this review, we summarized and compared colorectal cancer incidence among different Asian American subgroups, and to explore the reasons behind the heterogeneity. Based on limited literatures, we found that Japanese Americans have the highest colorectal cancer incidence among all Asian Americans. The incidence is decreasing among most Asian American subgroups except for Korean Americans. Such heterogeneity is influenced by lifestyle factors related to the country of origin and the United States, as well as colorectal cancer screening.
Exclusive breastfeeding for the first 3 months of life may reduce the risk of respiratory allergies and some asthma in children at the age of 6 years
Authors: Bigman Galya
Published: March 2020

Aim

We examined the associations between breastfeeding and respiratory allergies and types of asthma in American children.

Methods

This longitudinal study used data from mother‐infant pairs who took part in the Infant Feeding Practices Study II in 2005‐2007 and the Year 6 Follow‐Up Study in 2012. The mothers reported breastfeeding practices on a monthly basis for the first year of life, childhood asthma and allergies at age 6 years, and associated factors. Generalised linear models were used in statistical analyses.

Results

Overall, 1177 mother‐infant pairs were included in the sample. A third (32.9%) of the children were exclusively breastfed until the age of 3 months and by the age of 6 years 20.8% had been diagnosed with respiratory allergies and 11.3% with asthma. In the multivariable analyses, exclusive breastfeeding for 3 months was associated with a reduced relative risk of respiratory allergies of 0.77 at the age of 6 years. It also reduced the relative risk of asthma to 0.66, but only if the children did not have a family history of asthma.

Conclusion

This longitudinal study provided evidence that exclusive breastfeeding for the first 3 months may reduce the risk of respiratory allergies and asthma in children 6 years of age, but concerning asthma, statistical significance was reached only in children without a family predisposition to asthma.
Integrative policy development for healthier people and ecosystems: A European case analysis
Authors: White Piran C. L. , Guégan Jean‐François , Keune Hans , De Bell Sian , Geijzendorffer Ilse R. , Hermans Tia , Prieur‐Richard Anne‐Hélène , Iroegbu Chinny , Stone Dave , Vanwambeke Sophie , de Vries Sjerp , Ford Adriana , Graham Hilary
Published: March 2020

There is growing evidence of the inter‐relationships between ecosystems and public health. This creates opportunities for the development of cross‐sectoral policies and interventions that provide dual benefits to public health and to the natural environment. These benefits are increasingly articulated in strategy documents at national and regional level, yet implementation of integrative policies on the ground remains limited and fragmented. Here, we use a workshop approach to identify some features of this evidence–implementation gap based on policy and practice within a number of western European countries. The driving forces behind some recent moves towards more integrative policy development and implementation show important differences between countries, reflecting the non‐linear and complex nature of the policy‐making process. We use these case studies to illustrate some of the key barriers to greater integrative policy development identified in the policy analysis literature. Specific barriers we identify include: institutional barriers; differing time perspectives in public health and ecosystem management; contrasting historical development of public health and natural environment disciplinary policy agendas; an incomplete evidence base relating investment in the natural environment to benefits for public health; a lack of appropriate outcome measures including benefit–cost trade‐offs; and finally a lack of integrative policy frameworks across the health and natural environment sectors. We also identify opportunities for greater policy integration and examples of good practice from different countries. However, we note there is no single mechanism that will deliver integrative policy for healthier people and ecosystems in all countries and situations. National governments, national public agencies, local governments, research institutions, and professional bodies all share a responsibility to identify and seize opportunities for influencing policy change, whether incremental or abrupt, to ensure that ecosystems and the health of society are managed so that the interests of future generations, as well as present generations, can be protected.
Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry
Authors: Català Albert , Ali Salah S. , Cuvelier Geoffrey D. E. , Steele MacGregor , Klaassen Robert J. , Fernandez Conrad V. , Pastore Yves D. , Abish Sharon , Rayar Meera , Jardine Lawrence , Breakey Vicky R. , Brossard Josee , Sinha Roona , Silva Mariana , Goodyear Lisa , Lipton Jeffrey H. , Michon Bruno , Corriveau‐Bourque Catherine , Sung Lillian , Lauhasurayotin Supanun , Zlateska Bozana , Cada Michaela , Dror Yigal
Published: March 2020

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.
Effect of direct‐acting oral anticoagulants (DOACs) on bleeding and blood product usage in cardiac surgery compared to warfarin and controls
Authors: Little Christopher , Szydlo Richard , Aw TC , Laffan Mike , Arachchillage Deepa R. J.
Published: March 2020

In this retrospective, single‐centre, observational study, we assessed (i) use of anticoagulant and antiplatelet (AP) therapy, (ii) the duration of direct‐acting oral anticoagulant (DOAC) discontinuation, (iii) renal function and (iv) PT and APTT as predictors of bleeding and blood product usage; in adults (>18 years) undergoing major cardiac surgery from 01.01.2015 to 31.12.2018. Comparisons were made between each treatment group (warfarin, DOAC and DOAC + AP) and untreated controls, and between warfarin and DOAC. A total of 2928 patients were included for analysis. Median (range) of DOAC discontinuation prior to surgery was five days (1–22) for DOAC and five days (2–7) for DOAC + AP. There were no differences in bleeding between anticoagulant groups versus control, or DOAC versus warfarin. There were no differences in blood product use between DOAC and warfarin patients. The duration of DOAC discontinuation but not the creatinine clearance influenced bleeding and blood products use. Thrombosis occurred in 0·7% and 3·1% in controls and patients on warfarin respectively (P = 0·099) with none among patients on DOAC or DOAC + AP. The PT/APTT had no predictive value. Median five‐day discontinuation of DOAC +/− AP irrespective of renal function prevents an increase in bleeding compared to patients on warfarin or controls with no increase in thrombosis.