bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the translational machinery in gastrointestinal stromal tumors (GIST) – a new therapeutic vulnerability
Authors: Lee Donna M. , Sun Angela , Patil Sneha S. , Liu Lijun , Rao Aparna , Trent Parker , Ali Areej A. , Liu Catherine , Rausch Jessica L. , Presutti Laura , Kaczorowski Adam , Schneider Felix , Amankulor Nduka , Shuda Masahiro , Duensing Anette
Published: September 2021

Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Resistance mechanisms mainly involve secondary mutations in the KIT receptor tyrosine kinase gene indicating continued dependency on the KIT signaling pathway. The fact that the type of secondary mutation confers either sensitivity or resistance towards TKIs and the notion that secondary mutations exhibit intra- and intertumoral heterogeneity complicates the optimal choice of treatment in the imatinib-resistant setting. Therefore, new strategies that target KIT independently of its underlying mutations are urgently needed. Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthesis and is FDA-approved for the treatment of chronic myeloid leukemia (CML) that is resistant to at least two TKIs. HHT has also shown activity in KIT-mutant mastocytosis models, which are intrinsically resistant to imatinib and most other TKIs. We hypothesized that HHT could be effective in GIST through downregulation of KIT expression and subsequent decrease of KIT activation and downstream signaling. Testing several GIST cell line models, HHT led to a significant reduction in nascent protein synthesis and was highly effective in the nanomolar range in IM-sensitive and IM-resistant GIST cell lines. HHT treatment resulted in a rapid and complete abolishment of KIT expression and activation, while KIT mRNA levels were minimally affected. The response to HHT involved induction of apoptosis as well as cell cycle arrest. The antitumor activity of HHT was confirmed in a GIST xenograft model. Taken together, inhibition of protein biosynthesis is a promising strategy to overcome TKI resistance in GIST.
Transcriptional control of hypoxic hyphal growth in the fungal pathogen Candida albicans
Authors: Henry Manon , Burgain Anais , Tebbji Faiza , Sellam Adnane
Published: September 2021

Background

The ability of Candida albicans, an important human fungal pathogen, to develop filamentous forms is a crucial determinant for host invasion and virulence. Filamentation is triggered by different host environmental cues. Hypoxia, the dominant conditions that C. albicans encounters inside the human host, promote filamentation, however, the contributing mechanisms remain poorly characterized.

Methods

We performed a quantitative analysis of gene deletion mutants from different collections of protein kinases and transcriptional regulators in C. albicans to identify specific modulators of the hypoxic filamentation. We used genome-wide transcriptional profiling (Microarrays) and promoter occupancy (ChIP-chip) to characterize regulons of two transcription factors that were associated with the hypoxic filamentation. Genetic interactions were also used to assess functional relationships among the newly identified modulators of hypoxic filamentation and the well-known C. albicans core morphogenetic regulators.

Results

Our genetic screen uncovered two transcription factors, Ahr1 and Tye7, that act as prominent regulators of C. albicans filamentation specifically under hypoxia. Both ahr1 and tye7 mutants exhibited a hyperfilamentous phenotype specifically under an oxygen-depleted environment suggesting that these transcription factors act as negative regulators of hypoxic filamentation. By combining microarray and ChIP-chip data, we have characterized the set of genes that are directly modulated by Ahr1 and Tye7. We found that both Ahr1 and Tye7 modulate a different set of genes and biological processes. Our genetic epistasis analysis supports our genomic finding and suggests that Ahr1 and Tye7 act independently to modulate hyphal growth in response to hypoxia. Furthermore, our genetic interaction experiments uncovered that Ahr1 and Tye7 repress the hypoxic filamentation growth via the Efg1 and Ras1/Cyr1 pathways, respectively.

Conclusion

In sum, this investigation represents an informative resource toward the understanding of how hypoxia, the predominant condition inside the host, shapes the invasive filamentous growth of C. albicans.
Offspring of first-generation hatchery steelhead trout (Oncorhynchus mykiss) grow faster in the hatchery than offspring of wild fish, but survive worse in the wild: possible mechanisms for inadvertent domestication and fitness loss in hatchery salmon
Authors: Blouin Michael S , Wrey Madeleine C , Bollmann Stephanie R. , Skaar James C. , Twibell Ronald , Fuentes Claudio
Published: September 2021

Salmonid fish raised in hatcheries often have lower fitness (number of returning adult offspring) than wild fish when both spawn in the wild. Body size at release from hatcheries is positively correlated with survival at sea. So one explanation for reduced fitness is that hatcheries inadvertently select for trait values that enhance growth rate under the unnatural environment of a hatchery, but that are maladaptive in the wild environment. A simple prediction of this hypothesis is that juveniles of hatchery origin should grow more quickly than fish of wild origin under hatchery conditions, but should have lower survival under wild conditions. We tested that hypothesis using multiple full sibling families of steelhead (Oncorhynchus mykiss) that were spawned using either two wild parents (WxW) or two first-generation hatchery (HxH) parents. Offspring from all the families were grown together under hatchery conditions and under semi-natural conditions in artificial streams. HxH families grew significantly faster in the hatchery, but had significantly lower survival in the streams. That we see this tradeoff after only a single generation of selection suggests that the traits involved are under very strong selection. We also considered one possible alteration to the hatchery environment that might reduce the intensity of selection among families in size at release. Here we tested whether reducing the fat content of hatchery feed would reduce the variance among families in body size. Although fish raised under a low-fat diet were slightly smaller, the variation among families in final size was unchanged. Thus, there is no evidence that reducing the fat content of hatchery feed would reduce the opportunity for selection among families on size at release.
Systems analysis shows a role of cytophilic antibodies in shaping innate tolerance to malaria
Authors: Lautenbach Maximilian Julius , Yman Victor , Kadri Nadir , Plaza David Fernando , Angenendt Sina , Sondén Klara , Färnert Anna , Sundling Christopher
Published: September 2021

The mechanism of acquisition and maintenance of natural immunity against Plasmodium falciparum malaria remains unclear. Although, clinical immunity develops over time with repeated malaria episodes, disease tolerance is more rapidly acquired compared to protective immunity. It remains unclear, how pre-existing immune responses impacts the mechanism responsible for disease tolerance. Here, we investigated a cohort of returning travelers treated for acute symptomatic P. falciparum malaria, either infected for the first time, or with a previous history of malaria. Through repeated sampling over one year in a malaria free setting, we were able to study the acute and longitudinal effects of the infection. We combined comprehensive immune cell and plasma protein profiling with integrated and data driven analysis, describing the immune landscape from acute disease to one year after infection. We identified a strong association between pro-inflammatory signatures and γδ T cell expansion. The association was significantly impacted by previous exposure to malaria, resulting in a dampened pro-inflammatory response, which translated to reduced Vδ2+ γδ T cell expansion compared to primary infected individuals. The dampened inflammatory signal was associated with early expansion of FcγRIII+ monocytes and parasite-specific antibodies of IgG1 and IgG3 isotypes.

Our data suggest that the interplay of FcγRIII+ monocytes and a cytophilic parasite-specific IgG during the early blood stage infection lead to lower parasitemia and a dampened pro-inflammatory response with reduced γδ T cell expansion. This enhanced control and reduced inflammation points to a potential mechanism on how tolerance is established following repeated malaria exposure.

One Sentence Summary

A systems immunology analysis on natural malaria sheds light on disease tolerance mechanism associated with gamma delta T cell expansion
A resource for improved predictions ofTrypanosomaandLeishmaniaprotein three-dimensional structure
Authors: Wheeler Richard John
Published: September 2021

AlphaFold2 and RoseTTAfold represent a transformative advance for predicting protein structure. They are able to make very high-quality predictions given a high-quality alignment of the protein sequence with related proteins. These predictions are now readily availableviathe AlphaFold database of predicted structures and AlphaFold/RoseTTAfold Colaboratory notebooks for custom predictions. However, predictions for some species tend to be lower confidence than model organisms. This includesTrypanosoma cruziandLeishmania infantum: important unicellular eukaryotic human parasites in an early-branching eukaryotic lineage. The cause appears to be due to poor sampling of this branch of life in the protein sequences databases used for the AlphaFold database and ColabFold. Here, by comprehensively gathering openly available protein sequence data for species from this lineage, significant improvements to AlphaFold2 protein structure prediction over the AlphaFold database and ColabFold are demonstrated. This is made available as an easy-to-use tool for the parasitology community in the form of Colaboratory notebooks for generating multiple sequence alignments and AlphaFold2 predictions of protein structure forTrypanosoma,Leishmaniaand related species.
Distal-lessandspaltare distal organisers of pierid wing patterns
Authors: Qi Wee Jocelyn Liang , Banerjee Tirtha Das , Prakash Anupama , Seah Kwi Shan , Monteiro Antónia
Published: September 2021

Two genes,Distal-less (Dll)andspalt (sal), are known to be involved in establishing nymphalid butterfly wing patterns. They function in several ways: in the differentiation of the eyespot’s central signaling cells, or foci; in the differentiation of the surrounding black disc; in overall scale melanisation (Dll); and in elaborating marginal patterns, such as parafocal elements. However, little is known about the functions of these genes in the development of wing patterns in other butterfly families. Here, we study the expression and function ofDllandsalin the development of spots and other melanic wing patterns of the Indian cabbage white,Pieris canidia, a pierid butterfly. InP. canidia, both Dll and Sal proteins are expressed in the scale-building cells at the wing tips, in chevron patterns along the pupal wing margins, and in areas of future scale melanisation. Additionally,Sal alone is expressed in the future black spots. CRISPR knockouts ofDllandsalshowed that each gene is required for the development of melanic wing pattern elements, and repressing pteridine granule formation, in the areas where they are expressed. We conclude that both genes likely play ancestral roles in organising distal butterfly wing patterns, across pierid and nymphalid butterflies, but are unlikely to be differentiating signalling centers in pierids black spots. The genetic and developmental mechanisms that set up the location of spots and eyespots are likely distinct in each lineage.
What do we know about survival of Common cranes? An elementary introduction with Euring databank
Authors: Bautista Luis M. , Alonso Juan C.
Published: September 2021

The increase of the western populations of Common cranes (Grus grus) in the last five decades highlights the need to estimate survival rates. According to Euring databank (EDB), the oldest Common crane ever known was 27 years old in year 2017. This lifespan was obtained by means of 24,900 recoveries of 2,124 ringed cranes collected between years 1936 and 2017. Nearly all cranes were ringed and observed in the last 30 years, and therefore the elapsed time was not enough to reach the maximum longevity reported for the species in captivity (43 years, Mitchell 1911). Life expectancy was five years on average after the ring was attached. Here we provide some elementary analyses to calculate the annualapparentsurvival rate (ϕ = 0.85) and the annual encounter probability (p= 0.45) of Common cranes, as a first step to advance in the knowledge of the species’ population dynamics. The great increase of breeding and wintering crane populations in western Europe in the last decades remains largely unexplained.
Mate choice enhances post-zygotic barriers to gene flow via ancestry bundling
Authors: Muralidhar Pavitra , Coop Graham , Veller Carl
Published: September 2021

Hybridization and subsequent genetic introgression are now known to be common features of the histories of many species, including our own. Following hybridization, selection often purges introgressed DNA genome-wide. While mate choice can prevent hybridization in the first place, it is also known to play an important role in post-zygotic selection against hybrids, and thus the purging of introgressed DNA. However, this role is usually thought of as a direct one: a mating preference for conspecifics reduces the sexual fitness of hybrids, reducing the transmission of introgressed ancestry. Here, we explore a second, indirect role of mate choice as a barrier to gene flow. Under assortative mating, parents covary in their ancestry, causing ancestry to be “bundled” in their offspring and later generations. This bundling effect increases ancestry variance in the population, enhancing the efficiency with which post-zygotic selection purges introgressed DNA. Using whole-genome simulations, we show that the bundling effect can comprise a substantial portion of mate choice’s overall effect as a post-zygotic barrier to gene flow, and that it is driven by ancestry covariances between and within maternally and paternally inherited genomes. We derive a simple method for estimating the impact of the bundling effect from standard measures of assortative mating. Applying this method to data from a diverse set of hybrid zones, we find that the bundling effect increases the purging of introgressed DNA by between 1.2-fold (in a baboon system with weak assortative mating) and 14-fold (in a swordtail system with strong assortative mating). Thus, the bundling effect of mate choice contributes substantially to the genetic isolation of species.
Transendothelial migration induces differential migration dynamics of leukocytes in tissue matrix
Authors: van Steen Abraham C.I. , Kempers Lanette , Schoppmeyer Rouven , Blokker Max , Beebe David J. , Nolte Martijn A. , van Buul Jaap D.
Published: September 2021

Leukocyte extravasation into inflamed tissue is a complex process that is difficult to capture as a whole in vitro. We employed a blood-vessel-on-a-chip model in which endothelial cells were cultured in a tube-like lumen in a collagen-1 matrix. The vessels are leak-tight, creating a barrier for molecules and leukocytes. Addition of inflammatory cytokine TNF-α caused vasoconstriction, actin remodelling and upregulation of ICAM-1. Introducing leukocytes into the vessels allowed real-time visualisation of all different steps of the leukocyte transmigration cascade including migration into the extracellular matrix. Individual cell tracking over time distinguished striking differences in migratory behaviour between T-cells and neutrophils. Neutrophils cross the endothelial layer more efficiently than T-cells, but upon entering the matrix, neutrophils display high speed but low persistence, whereas T-cells migrate with low speed and rather linear migration. In conclusion, 3D imaging in real-time of leukocyte extravasation in a vessel-on-a-chip enables detailed qualitative and quantitative analysis of different stages of the full leukocyte extravasation process in a single assay.

A functional hydrogel-based blood-vessel-on-a-chip model is used to study the complete leukocyte transendothelial migration process in real time. T-lymphocytes and neutrophils exhibit distinct migration dynamics in the extravascular matrix after transendothelial migration, which can be altered using a chemotactic gradient.
Nutrient availability shifts the biosynthetic potential of soil-derived microbial communities
Authors: Chevrette Marc G , Himes Bradley , Carlos-Shanley Camila
Published: September 2021

Secondary metabolites produced by microorganisms are the main source of antimicrobials other pharmaceutical drugs. Soil microbes have been the primary discovery source for these secondary metabolites, often producing complex organic compounds with specific biological activities. Research suggests that secondary metabolism broadly shapes microbial ecological interactions, but little is known about the factors that shape the abundance, distribution, and diversity of biosynthetic gene clusters in the context of microbial communities. In this study, we investigate the role of nutrient availability on the abundance of biosynthetic gene clusters in soil-derived microbial consortia. We found that soil microbial consortia enriched in medium with 150 mg/L of glucose and 200 mg/L of trehalose (here defined as high sugar) had more biosynthetic gene cluster and higher inhibitory activity than soil microbial consortia enriched in medium with 15 mg/L of glucose + 20 mg/L of trehalose (here defined as low sugar). Our results demonstrate that laboratory microbial communities are a promising tool to study ecology of specialized metabolites.
Defective Desmosomal Adhesion Causes Arrhythmogenic Cardiomyopathy by involving an Integrin-αVβ6/TGF-β Signaling Cascade
Authors: Schinner Camilla , Franz Henriette , Zimmermann Aude , Wanuske Marie-Therès , Geier Florian , Pelczar Pawel , Lorenz Vera , Xu Lifen , Stüdle Chiara , Maly Piotr I , Kauferstein Silke , Beckmann Britt Maria , Kuster Gabriela M , Spindler Volker
Published: September 2021

Background

Arrhythmogenic Cardiomyopathy (ACM) is characterized by progressive loss of cardiomyocytes with fibrofatty replacement, systolic dysfunction and life-threatening arrhythmias. A substantial proportion of ACM is caused by mutations in genes of the desmosomal cell-cell adhesion complex, but the underlying mechanisms are not well understood. So far, treatment options are only symptomatic. Here, we investigate the relevance of defective desmosomal adhesion for ACM development and progression.

Methods

We mutated the binding site of desmoglein-2 (DSG2), a crucial desmosomal adhesion molecule in cardiomyocytes. This DSG2-W2A mutation abrogates the tryptophan swap, a central interaction mechanism of DSG2 based on structural data. Impaired adhesive function of DSG2-W2A was confirmed by cell-cell dissociation assays and force spectroscopy measurements by atomic force microscopy. We next generated a DSG2-W2A knock-in mouse model, which was analyzed by echocardiography and histological and bio-molecular techniques including RNA sequencing, transmission electron and super-resolution microscopy. The results were compared to ACM patient samples and their relevance was confirmed in cardiac slice cultures.

Results

The DSG2-W2A mutation induced impaired binding and desmosomal adhesion dysfunction on cellular and molecular level. Mice bearing this mutation develop a severe cardiac phenotype recalling the characteristics of ACM, including cardiac fibrosis, impaired systolic function and arrhythmia. A comparison of the transcriptome of mutant mice with ACM patient data suggested deregulated integrin-αVβ6 and subsequent TGF-β signaling as driver of cardiac fibrosis. Accordingly, blocking antibodies targeting integrin-αVβ6 or inhibition of TGF-β receptor signaling both led to reduced expression of pro-fibrotic markers in cardiac slice cultures.

Conclusions

Here, we show that disruption of desmosomal adhesion is sufficient to induce ACM, which confirms the dysfunctional adhesion hypothesis. Mechanistically, deregulation of integrin-αVβ6 signaling was identified as a central step towards fibrosis. This highlights the value of this model to discern mechanisms of cardiac fibrosis and to identify and test novel treatment options for ACM.
Genetic and genomic architecture in eight strains of the laboratory opossumMonodelphis domestica
Authors: Xiong Xiao , Samollow Paul B. , Cao Wenqi , Metz Richard , Zhang Chao , Leandro Ana C. , VandeBerg John L. , Wang Xu
Published: September 2021

The gray short-tailed opossum is an established laboratory-bred marsupial model for biomedical research. It serves as a critical species for comparative genomics research, providing the pivotal phylogenetic outgroup for studies of derived vs. ancestral states of genomic/epigenomic characteristics for all eutherian mammal lineages. To characterize the current genetic profile of this laboratory marsupial, we examined 79 individuals from eight established laboratory strains. Double digest restriction-site associated DNA sequencing (ddRAD-seq) and whole-genome resequencing experiments were performed to investigate the genetic architecture in these strains. A total of 66,640 high-quality single nucleotide polymorphisms (SNPs) were identified. We analyzed SNP density, average heterozygosity, nucleotide diversity, and population differentiation parameter Fst within and between the eight strains. Principal component and population structure analysis clearly resolve the strains at the level of their ancestral founder populations, and the genetic architecture of these strains correctly reflects their breeding history. We confirmed the successful establishment of the first inbred laboratory opossum strain LSD (inbreeding coefficient F > 0.99) and a nearly inbred strain FD2M1 (0.98 < F < 0.99), each derived from a different ancestral background. These strains are suitable for various experimental protocols requiring controlled genetic backgrounds and for intercrosses and backcrosses that can generate offspring with informative SNPs for studying a variety of genetic and epigenetic processes. Together with recent advances in reproductive manipulation and CRISPR/Cas9 techniques forM. domestica, the existence of distinctive inbred strains will enable genome editing on different genetic backgrounds, greatly expanding the utility of this marsupial model for biomedical research.
A high resolution single molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis
Authors: Zhang Runxuan , Kuo Richard , Coulter Max , Calixto Cristiane P. G. , Entizne Juan Carlos , Guo Wenbin , Marquez Yamile , Milne Linda , Riegler Stefan , Matsui Akihiro , Tanaka Maho , Harvey Sarah , Gao Yubang , Wießner-Kroh Theresa , Crespi Martin , Denby Katherine , Hur Asa ben , Huq Enamul , Jantsch Michael , Jarmolowski Artur , Koester Tino , Laubinger Sascha , Li Qingshun Quinn , Gu Lianfeng , Seki Motoaki , Staiger Dorothee , Sunkar Ramanjulu , Szweykowska-Kulinska Zofia , Tu Shih-Long , Wachter Andreas , Waugh Robbie , Xiong Liming , Zhang Xiao-Ning , Reddy Anireddy S.N. , Barta Andrea , Kalyna Maria , Brown John WS
Published: September 2021

Background

Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single molecule long read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation or incomplete cDNA synthesis.

Results

We present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 160k transcripts - twice that of the best current Arabidopsis transcriptome and including over 1,500 novel genes. 79% of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We developed novel methods to determine splice junctions and transcription start and end sites accurately. Mis- match profiles around splice junctions provided a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identified high confidence transcription start/end sites and removed fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provided higher resolution of transcript expression profiling and identified cold- and light-induced differential transcription start and polyadenylation site usage.

Conclusions

AtRTD3 is the most comprehensive Arabidopsis transcriptome currently available. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single molecule sequencing analysis from any species.
Wildlife in Cameroon harbor diverse coronaviruses including many isolates closely related to human coronavirus 229E
Authors: Ntumvi Nkom F. , Ndze Valantine Ngum , Gillis Amethyst , Doux Diffo Joseph Le , Tamoufe Ubald , Takuo Jean-Michel , Mouiche Moctar M. M. , Nwobegahay Julius , LeBreton Matthew , Rimoin Anne W. , Schneider Bradley S. , Monagin Corina , McIver David J. , Roy Sanjit , Ayukekbong James A. , Saylors Karen , Joly Damien O. , Wolfe Nathan D. , Rubin Edward M. , Lange Christian E.
Published: September 2021

Zoonotic spillover of animal viruses into human populations is a continuous and increasing public health risk. SARS-CoV-2 highlights the global impact emergence events can have. Considering the history and diversity of coronaviruses (CoVs), especially in bats, SARS-CoV-2 will likely not be the last to spillover from animals into human populations.

We sampled and tested wildlife in the central African country Cameroon to determine which CoVs are circulating and how they relate to previously detected human and animal CoVs. We collected animal and ecological data at sampling locations and used family-level consensus PCR combined with amplicon sequencing for virus detection.

Between 2003 and 2018, samples were collected from 6,580 animals of several different orders. CoV RNA was detected in 175 bats, a civet, and a shrew. The CoV RNAs detected in the bats represented 17 different genetic clusters, coinciding with alpha (n=8) and beta (n=9) CoVs. Sequences resembling human CoV-229E (HCoV-229E) were found in 40 Hipposideridae bats. Phylogenetic analyses place the human derived HCoV-229E isolates closest to those from camels in terms of the S and N genes, but closest to isolates from bats for the E, M, and RdRp genes. The CoV RNA positivity rate in bats varied significantly (p<0.001) between the wet (8.2%) and dry season (4.5%). Most sampled species accordingly had a wet season high and dry season low, while for some the opposite was found.

Eight of the suspected CoV species of which we detected RNA appear to be entirely novel CoV species, which suggests that CoV diversity in African wildlife is still rather poorly understood. The detection of multiple different variants of HCoV-229E-like viruses supports the bat reservoir hypothesis for this virus, with the phylogenetic results casting some doubt on camels as an intermediate host. The findings also support the previously proposed influence of ecological factors on CoV circulation, indicating a high level of underlying complexity to the viral ecology. These results indicate the importance of investing in surveillance activities among wild animals to detect all potential threats as well as sentinel surveillance among exposed humans to determine emerging threats.
“It needs to be the right blend”: a qualitative exploration of remote e-workers’ experience and well-being at work
Authors: Charalampous Maria , Grant Christine Anne , Tramontano Carlo
Published: September 2021

Purpose

This present qualitative study explores the impact of the remote e-working experience on employees’ well-being.

Design/methodology/approach

Forty (23 male) remote e-workers working for a British IT company were interviewed about their work-related well-being. Semi-structured interviews were framed within an existing theoretical of work-related well-being; hence, questions targeted five distinct dimensions of affective, professional, social, cognitive and psychosomatic well-being. However, data collection was not constrained by this model, allowing the exploration of other aspects interviewees considered relevant to their work-related well-being. Interview data were analysed using thematic analysis, where key themes emerged.

Findings

Findings support the relevance of a multidimensional approach to understanding remote e-workers’ well-being as it provides an in-depth understanding of the inter-connectedness between relevant dimensions. Further insight into the overlooked issues of detachment from work and health-related behaviours when e-working remotely is also provided.

Practical implications

This study proposes practical implications related to the organisational, managerial and individual level; providing individuals tailored guidance on how to remote e-work effectively and raising the importance of cultural change to support remote e-workers to be open about their working preferences.

Originality/value

An original contribution to the field of remote e-working is provided, by adopting a holistic approach to explore well-being, disentangling the interconnections between different well-being dimensions and discussing pivotal contributing factors that seemed to be understudied within extant remote e-working literature.
Assessing audit outcomes of pre-determined objectives in a public institution (South Africa)
Authors: Mosimege Stella Banyana , Masiya Tyanai
Published: September 2021

Purpose

Many developing countries such as South Africa have been introducing measurement of results to improve public service delivery. The practice of development of performance measures in the public service emanates from pressure exerted by citizens who are calling for more efficiency and effectiveness in delivering services. This article examines the implementation of the audit of pre-determined objectives at the Department of Basic Education (DBE).

Design/methodology/approach

This study is based on a qualitative case study approach. Secondary sources of data were used in order to analyse the DBE's challenges in managing performance information. Key secondary documents used include the AGSA annual audit reports as well as the DBE 2010/11–2014/15 Strategic Plan and Annual Performance Plans (APP) that provide the pre-determined objectives selected by the Department to measure performance for the five-year period.

Findings

The findings indicate that there are shortcomings in the processes of managing performance information. Based on the findings, it is incumbent upon the senior management of the DBE to strive towards understanding and improving their oversight roles and responsibilities in the management of pre-determined objectives.

Originality/value

The study generates a deeper understanding of what has been happening when pre-determined objectives were developed, reported or assessed in the DBE. This will assist the Department and similar public institutions to make further improvements in order to achieve pre-determined objectives.
Growing pains – a case study from higher education
Authors: Kyvik Oyvin
Published: September 2021

Theoretical basis

The teaching case study is based on a (real-life) complex organizational and strategic context, and several bodies of literature may be used to interpret, analyze, explore and discuss alternative solutions. Among several relevant theoretical basis are (educational) leadership, strategy, institutional change, organization, practice orientation of education and organizational learning. The Instructors’ Manual gives suggestions as to how the case may be used in teaching and gives references to relevant literature.

Research methodology

The teaching case study is based on participatory action research. The narrative of the case is based on empirical observations in form of a research diary recording events, dialogues and discussion with colleagues and organizational leaders during a five-year period. The case study is based on real proceedings. But, the narrative is generic, and names are anonymized, and organizational contexts and events are disguised. Any similarities to real institutions are coincidental.

Case overview/synopsis

The case tells the story of Birk Grimson (PhD), a professional who returns to academia after many years of business practice in the private sector. He is struck by how different the work ambience is in academia and how bureaucracy and a rigid organizational structure seem to quell innovation, resulting in resistance to systematic learning, organizational development and strategic change.

Complexity academic level

The teaching case study is appropriate for business, organizational or administrative students at master’s, PhD level or executive education. For students with other disciplinary educational backgrounds (such as engineering, education or health care), some basic knowledge of organization and management or alternatively relevant experience is recommended.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.
Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications
Authors: Agusti Alvar , Fabbri Leonardo , Lahousse Lies , Singh Dave , Papi Alberto
Published: September 2021

A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long‐acting β2 adrenergic bronchodilators (LABA). The addition of long‐acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single‐inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS‐LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.
“The odds were stacked against me”: a qualitative study of underrepresented minorities in surgical training
Authors: Villanueva Claudia , Cain Justin , Greenhill Jennene , Nestel Debra
Published: September 2021

Background

The Royal Australasian College of Surgeons (RACS) is expected to provide surgical care to a diverse patient population across Australia and New Zealand (ANZ). To improve the quality‐of‐care individuals receive, the surgical workforce must reflect the population it serves. Achieving diversity within RACS will strengthen therapeutic relationships with patients and promote an inclusive culture. This study investigates the perspectives of underrepresented minority (URM) trainees to highlight barriers for the selection and completion of the RACS Surgical Education and Training (SET) program.

Methods

This qualitative study used online, semi‐structured, in‐depth interviews of URM trainees. Participants were recruited by self‐identification and were invited to participate based on inclusion criterion. Interviews took place between August and October 2020, were transcribed and de‐identified. Framework analysis was used to identify themes.

Findings

Eight participants from four surgical specialities were interviewed, six from Australia and two from New Zealand. There were six female and two male participants. The findings identified barriers that were grouped into eight broad areas: discouragement; structural racism, discrimination and unconscious bias; language barriers; policies and procedures; lack of role models; homophobia; sexual harassment and women in surgery.

Conclusion

The findings offer guidance to RACS and the surgical community to explore new strategies to improve the experience of URM SET trainees. While on a small scale, the study draws directly on the URMs' experiences to inform strategies addressing equity, diversity and inclusion. The aim is to produce a diverse surgical workforce that better delivers healthcare services to a diverse population.
Assessment of post‐surgical donor‐site morbidity in vastus lateralis free flap for head and neck reconstructive surgery: an observational study
Authors: Seth Ishith , Hewitt Lyndel , Yabe Takako , Dunn Masako , Wykes James , Clark Jonathan R. , Ashford Bruce
Published: September 2021

Background

Vastus lateralis (VL) can be used to reconstruct defects of the head and neck. Whilst the advantages are documented, donor‐site morbidity is not well described. This study aimed to assess donor‐site morbidity after VL flap harvest. Results will determine future directions for preventative and post‐operative care to improve patient health outcomes.

Methods

Ten participants (mean age 55 years) were assessed for the presence of donor‐site morbidity after VL harvest. Musculoskeletal (pain, muscle strength, muscle length and tactile sensation), quality of life (SF‐12), lower extremity function, gait (function and speed) and sit to stand were assessed using validated and standardized procedures. The outcomes were compared to age‐matched healthy reference values or to the non‐operative side. Analyses were conducted using descriptive statistics and non‐parametric tests.

Results

There was no difference in muscle strength (knee extension), muscle length, ability to sit‐to‐stand, or gait function (all P > 0.05). Knee flexor muscle strength was significantly less on the operated leg compared to the non‐operated leg (P = 0.02) and walking speed was slower than age‐matched healthy values (P < 0.001). Thigh tactile sensation was impaired in 89% of participants. Quality of life was significantly less for the physical health component of the SF‐12 (P < 0.001). The mental health component of the SF‐12 was similar to healthy controls (P = 0.256).

Conclusion

There was no effect on donor site morbidity with regards to knee extensor strength, pain, walking function, ability to sit‐to‐stand and muscle length. VL harvest affected donor‐site knee flexion strength, walking speed, tactile sensation and physical health‐related quality of life.
Emergency cervical cerclage in twin and singleton pregnancies with 0‐mm cervical length or prolapsed membranes
Authors: Freegard Georgina D. , Donadono Vera , Impey Lawrence W. M.
Published: September 2021

Introduction

Cervical cerclage is controversial in twin pregnancies, although recent data from the USA supports its use where “physical examination‐indicated”. Limited data exist, however, in the extreme situation of 0‐mm ultrasound‐measured cervical length or even prolapsed membranes. This research compares the success of emergency cervical cerclage in multiple and singleton pregnancies.

Material and methods

This is a retrospective cohort study of all such cerclages performed at a tertiary hospital over a 15‐year period. “Emergency” was where transvaginal ultrasound‐assessed cervical length was 0 mm, with amniotic membranes at or beyond the external cervical os. Exclusion criteria were clinical or biochemical evidence of infection, regular contractions, bleeding, ruptured membranes, or gestation beyond 24+0 weeks. The primary outcome, or “success”, was defined as birth >27+6 weeks of gestation, with the neonate alive 28 days later with no markers of adverse outcome (seizures, periventricular leukomalacia, intracranial hemorrhage more than Grade 2, or necrotizing enterocolitis). Demographic and cerclage variables were assessed against the primary outcome. Variables correlated with success were analyzed between multiple and singleton pregnancies. Comparison of all adverse outcomes was then adjusted using logistic regression.

Results

A total of 135 pregnancies were included (107 singletons and 28 multiples [all twins]). Success was achieved in 79 (58.5%; 57.9% in singletons, 60.7% in twins). Nulliparity, in utero transfer, symptoms, prolapsed membranes, and dilation more than 3 cm were predictors of failure, but twin pregnancy was not. After controlling for potential confounding variables, there was no significant difference in measures of success between singleton and twin pregnancies, apart from higher rates of neonatal unit admission.

Conclusions

Emergency cervical cerclage, even in extreme situations, is as effective in twin pregnancies as it is in singletons.
Examining self‐affirmation as a tactic for recruiting inactive women into exercise interventions
Authors: More Kimberly R. , Phillips Leigh Alison , Green Zoie , Mentzou Aikaterini
Published: September 2021

Recruitment of insufficiently active individuals into exercise interventions is difficult due to many different barriers, including motivational barriers and negative body image. The present study provided an initial conceptual test of whether self‐affirmation can help increase recruitment of insufficiently active women to an exercise intervention. Emerging adult women were randomly assigned to complete a self‐affirmation or control task prior to reading the same message concerning the consequences of inactivity. In addition to completing demographic and body image measures at baseline, U.S. undergraduate participants (N = 254) indicated their interest in registering for an intervention and their intention to exercise after the experimental manipulation. Data did not support hypotheses that (1) self‐affirmed women would find the message less threatening and less manipulative, (2) self‐affirmed women would have higher intentions to exercise, (3) self‐affirmed women would be more likely to register interest for a future exercise intervention, and (4) condition and body dissatisfaction would interact such that the intervention would be particularly beneficial for women with high body dissatisfaction. Results revealed that 70% of participants were unwilling to register for an exercise intervention, which indicates that other novel exercise intervention recruitment techniques need to be tested.
Tick paralysis in Australian birds caused by Ixodes holocyclus
Authors: Hill AG , Clark NJ , Tokonami F
Published: September 2021

Tick paralysis is an uncommon cause of neuromuscular paralysis affecting 0.12% of wild birds presented to Currumbin Wildlife Sanctuary, Queensland, with a strong seasonal predilection towards spring and summer. Clinical signs and progression of paralysis showed similarities to companion animals and were consistent across 20 species. Tick location, number of engorged ticks and number of clinical signs did not affect the outcome; however, all mortalities occurred within 4 days of admission. Treatment with canine‐derived tick antiserum resulted in clinical improvement within 24 h and a recovery rate of 73%. Average time to resolution of clinical signs was 4.3 days, with juvenile birds recovering more quickly than adults. The treatment and release of wild birds affected by tick paralysis are both achievable and rewarding, further research is required to establish treatment guidelines in birds.
Mimics and artefacts of measurable residual disease in a highly sensitive multicolour flow cytometry assay for B‐lymphoblastic leukaemia/lymphoma: critical consideration for analysis of measurable residual disease
Authors: Chatterjee Gaurav , Sriram Harshini , Ghogale Sitaram , Deshpande Nilesh , Khanka Twinkle , Girase Karishma , Verma Shefali , Arolkar Gauri , Dasgupta Niharika , Narula Gaurav , Shetty Dhanalaxmi , Dhamne Chetan , Moulik Nirmalya R. , Rajpal Sweta , Patkar Nikhil V. , Banavali Shripad , Gujral Sumeet , Subramanian Papagudi G. , Tembhare Prashant R.
Published: September 2021

High‐sensitivity multicolour flow cytometry (MFC)‐based B‐lymphoblastic leukaemia (B‐ALL) measurable residual disease (BMRD) assay is increasingly being used in clinical practice. Herein, we describe six consistently present low‐level populations immunophenotypically mimicking abnormal B‐ALL blasts in 441 BMRD samples from 301 children. These included CD19+CD123+ plasmacytoid dendritic cells differentiating from lymphoid precursors, CD10+ transitional B cells with CD10+/CD38dim‐to‐negative/CD20bright/CD45bright phenotype, CD19+ natural killer (NK) cells, CD73bright/CD10+ mesenchymal stromal/stem cells, CD73bright/CD34+ endothelial cells, and a CD34+CD38dim‐to‐negative/CD10−/CD20bright/CD45bright subset of mature B cells. We provide the proportions, comprehensive immunophenotype, and practical clues for proper identification of these low‐level populations. Knowledge regarding the presence and immunophenotype of these mimics is essential for accurate interpretation in high‐sensitivity MFC‐BMRD analysis.
Entry deterrence by cheap talk
Authors: Kim Jeong‐Yoo
Published: September 2021

The conventional wisdom is that an incumbent can deter the rival firm's entry by costly limit pricing but cannot deter entry by a costless signal, so‐called cheap talk. In this short paper, we show that an incumbent can deter entry of a potential competitor by cheap talk if there is another potential entrant producing complementary goods. In equilibrium, which is partially revealing, the incumbent can use publicly observable cheap talk that can deter entry of the rival firm with some positive probability.
A landscape‐scale framework to identify refugia from multiple stressors
Authors: Rojas Isabel M. , Jennings Megan K. , Conlisk Erin , Syphard Alexandra D. , Mikesell Jack , Kinoshita Alicia M. , West Krista , Stow Doug , Storey Emanuel , De Guzman Mark E. , Foote Diane , Warneke Alexandria , Pairis Amber , Ryan Sherry , Flint Lorraine E. , Flint Alan L. , Lewison Rebecca L.
Published: September 2021

From a conservation perspective, quantifying potential refugial capacity has been predominantly focused on climate refugia, which is critical for maintaining the persistence of species and ecosystems. However, protection from other stressors, such as human‐induced changes in fire and hydrology, that cause habitat loss, degradation, and fragmentation is also necessary to ensure that conservation efforts focused on climate are not undermined by other threats. Thus, conceptual and methodological advances for quantifying potential refugia from multiple anthropogenic stressors are important to support conservation efforts. We devised a new conceptual approach, the domains of refugia, for assessing refugial capacity that identifies areas where exposure to multiple stressors is low. In our framework, patterns of environmental variability (e.g., increased frequency of warm summers), thresholds of resilience, and extent and intensity of stressors are used to identify areas of potential refugia from a suite of ongoing anthropogenic stressors (e.g., changes in fire regime). To demonstrate its utility, we applied the framework to a Southern California landscape. Sites with high refugial capacity (super‐refugia sites) had on average 30% fewer extremely warm summers, 20% fewer fire events, 10% less exposure to altered river channels and riparian areas, and 50% fewer recreational trails than the surrounding landscape. Our results suggest that super‐refugia sites (∼8200 km2) for some natural communities are underrepresented in the existing protected area network, a finding that can inform efforts to expand protected areas. Our case study highlights how considering exposure to multiple stressors can inform planning and practice to conserve biodiversity in a changing world.