bluuebunny/crossref_metadata_2025 huggingface dataset:
Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditiselegans
Authors: Charar Chayki , Metsuyanim-Cohen Sally , Gruenbaum Yosef , Bar Daniel Z
Published: October 2020

Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation oflmn-1, the singleCaenorhabditis eleganslamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation oflmn-1restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.
Counterfactual Hypothesis Testing of Tumor Microenvironment Scenarios Through Semantic Image Synthesis
Authors: Li Daniel , Chen Jennifer , Ma Qiang , Xie Yubin , Liu Andrew , Cheung Justin , Gudjonson Herman , Nawy Tal , Pe’er Dana , Pe’er Itsik
Published: October 2020

Abstract

Recent multiplexed protein imaging technologies characterize cells, their spatial organization, and interactions within microenvironments at an unprecedented resolution. Although observational data can reveal spatial associations, it does not allow users to infer salient biological relationships and cellular interactions. To address this challenge, we develop a generative model that allows users to test hypotheses about the effect of cell-cell interactions on protein expression through in silico perturbation. Our Cell-Cell Interaction GAN (CCIGAN) model employs a generative adversarial network (GAN) architecture to generate high fidelity synthetic multiplexed images from semantic cell segmentations. Our approach is unique in that it learns relationships between all imaging channels simultaneously and yields biological insights from multiple imaging technologies in silico, capturing known tumor-immune cell interactions missed by other state-of-the-art GAN models.
Nature of active forces in tissues: how contractile cells can form extensile monolayers
Authors: Balasubramaniam Lakshmi , Doostmohammadi Amin , Saw Thuan Beng , Sankara Narayana Gautham Hari Narayana , Mueller Romain , Dang Tien , Thomas Minnah , Gupta Shafali , Sonam Surabhi , Yap Alpha S. , Toyama Yusuke , Mège René-Marc , Yeomans Julia , Ladoux Benoît
Published: October 2020

Actomyosin machinery endows cells with contractility at a single cell level. However, at a tissue scale, cells can show either contractile or extensile behaviour based on the direction of pushing or pulling forces due to neighbour interactions or substrate interactions. Previous studies have shown that a monolayer of fibroblasts behaves as a contractile system1while a monolayer of epithelial cells2,3or neural crest cells behaves as an extensile system.4How these two contradictory sources of force generation can coexist has remained unexplained. Through a combination of experiments using MDCK (Madin Darby Canine Kidney) cells, and in-silico modeling, we uncover the mechanism behind this switch in behaviour of epithelial cell monolayers from extensile to contractile as the weakening of intercellular contacts. We find that this switch in active behaviour also promotes the buildup of tension at the cell-substrate interface through an increase in actin stress fibers and higher traction forces. This in turn triggers a mechanotransductive response in vinculin translocation to focal adhesion sites and YAP (Yes-associated protein) transcription factor activation. Our studies also show that differences in extensility and contractility act to sort cells, thus determining a general mechanism for mechanobiological pattern formation during cell competition, morphogenesis and cancer progression.
Multiple Holins Contribute to Extracellular DNA Release inPseudomonas aeruginosaBiofilms
Authors: Hynen Amelia L. , Lazenby James J. , Savva George M. , McCaughey Laura C. , Turnbull Lynne , Nolan Laura M. , Whitchurch Cynthia B.
Published: October 2020

Bacterial biofilms are comprised of aggregates of cells encased within a matrix of extracellular polymeric substances (EPS). One key EPS component is extracellular DNA (eDNA), which acts as a ‘glue’, facilitating cell-cell and cell-substratum interactions. We have previously demonstrated that eDNA is produced inPseudomonas aeruginosabiofilms via explosive cell lysis. This phenomenon involves a subset of the bacterial population explosively lysing, due to peptidoglycan degradation by the endolysin Lys. Here we demonstrate that inP. aeruginosathree holins, AlpB, CidA and Hol, are involved in Lys-mediated eDNA release within both submerged (hydrated) and interstitial (actively expanding) biofilms, albeit to different extents, depending upon the type of biofilm and the stage of biofilm development. We also demonstrate that eDNA release events determine the sites at which cells begin to cluster to initiate microcolony formation during the early stages of submerged biofilm development. Furthermore, our results show that sustained release of eDNA is required for cell cluster consolidation and subsequent microcolony development in submerged biofilms. Overall, this study adds to our understanding of how eDNA release is controlled temporally and spatially withinP. aeruginosabiofilms.
GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells
Authors: Fernandez Rafael J , Gardner Zachary J G , Slovik Katherine J , Liberti Derek C , Estep Katrina N , Yang Wenli , Chen Qijun , Santini Garrett T , Perez Javier V , Root Sarah , Bhatia Ranvir , Tobias John W , Babu Apoorva , Morley Michael P , Frank David B , Morrisey Edward E , Lengner Christopher J , Johnson F. Brad
Published: October 2020

Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human iPSC-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured DC mutant iAT2 cells accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC related pathologies.
“Being on the wrong side of the digital divide”: seeking technological interventions for education in Northeast Nigeria
Authors: Martens Marianne , Hajibayova Lala , Campana Kathleen , Rinnert Gretchen Caldwell , Caniglia Joanne , Bakori Isa Garba , Kamiyama Tsukuru , Mohammed Liman Audu , Mupinga Davison M. , Oh Olivia Jeonghwa
Published: October 2020

Purpose

This paper aims to report the initial findings of a project aiming to re-establish basic education in conflict-ravaged states in Northeastern Nigeria and to improve education providers' ability to plan and deliver basic educational services. The authors present a preliminary analysis of Nigerian teachers' access to information communication technology (ICT), their technology skills, as well associated national ICT policies.

Design/methodology/approach

This case study uses results from two co-designed tools, administered using KoboToolbox to Education Managers in the first instance, and teachers in the second. The data from the tools form the basis for analysis.

Findings

In the first instance, educational managers reported a lack of access to technology, the internet and to training and professional development. In the second instance, teachers reported issues present in the classroom environment, including poor infrastructure, a lack of resources and over-crowded classrooms. Very few teachers had access to computers or to the internet.

Research limitations/implications

The 33 educational managers represent a small sample size and may not be fully representative of the region covered. The ICT Capacity Audit tool listed Excel in two different areas – basic Excel skills and using Excel for data analysis – which could have caused confusion for participants. The data collection should be repeated, expanded and compared for consistency. For the team, changes to the proposed (SENSE) box content meant that we were not able to deliver low-tech tools, such as Boogie Boards, or high-tech tools, such as tablets, to schools.

Originality/value

Despite seemingly insurmountable challenges, the research team identified low-tech tools as a feasible resource in the classroom. Existing tools, such as teachers' smartphones and use of the WhatsApp application, can be used for sharing educational resources and providing teacher training. This paper argues that Nigeria needs up-to-date national ICT policies to guide in-country efforts to develop implementation of information technology initiatives for education.
Safety plugins for risks prevention through design resourcing BIM
Authors: Rodrigues Fernanda , Antunes Flávio , Matos Raquel
Published: October 2020

Purpose

The use of building information modelling (BIM) methodology has been increasing in the architecture, engineering, construction and operation sector, driven to a new paradigm of work with the use of three-dimensional (3D) parametric models. However, building information modelling (BIM) has been mostly used for as-built models of a building, not yet been widely used by designers during project and construction phases for occupational risks prevention and safety planning. This paper aims to show the capacity of developing tools that allow adding functionalities to Revit software to improve safety procedures and reduce the time spent on modelling them during the design phase.

Design/methodology/approach

To reach this objective, a structural 3D model of a building is used to validate the developed tools. A plugin prototype based on legal regulations was developed, allowing qualitative safety assessment through the application of job hazard analysis (JHA), SafeObject and checklists. These tools allow the automated detection of falls from height situations and the automated placement of the correspondent safety systems.

Findings

Revit application programming interface allowed the conception and addition of several functionalities that can be used in BIM methodology, and more specifically in the prevention of occupational risks in construction, contributing this paper to the application of a new approach to the prevention through design.

Originality/value

This paper is innovative and important because the developed plugins allowed: automated detection of potential falls from heights in the design stage; automated introduction of safety objects from a BIM Safety Objects Library; and the intercommunication between a BIM model and a safety database, bringing JHA integration directly on the project. The prototype of this work was validated for fall from height hazards but can be extended to other potentials hazards since the initial design stage.
Residents’ perception towards tourism impacts in Kashmir
Authors: Charag Asif Hamid , Fazili Asif Iqbal , Bashir Irfan
Published: October 2020

Purpose

The purpose of this study is to understand the residents’ perception towards environmental, social, cultural and economic impacts of tourism development in Kashmir.

Design/methodology/approach

The research instrument containing 27 items pertaining to six variables is adopted from the literature. A mix-method survey approach is used to solicit residents’ perceptions regarding environmental, social, cultural and economic impacts of the current level of tourism development. A total of 326 useful responses were subjected to descriptive statistics, analysis of variance (ANOVA) and post hoc analysis using SPSS (Version 22.0).

Findings

In general, the negative and positive impacts of tourism development are well perceived by the residents. The results indicate that the residents display positive perception regarding economic impacts, however, social and environmental impacts are negatively perceived. Furthermore, barring level of education, the study found no significant difference in the residents’ perception towards tourism impacts (environmental, social, cultural, economic, quality of life and cost of living).

Research limitations/implications

The paper identifies perceived impacts and issues of tourism development thereby, proposing possible mitigating measures. Also, the study identifies the need to develop a comprehensive policy framework addressing the issues related to the resident’s negative feelings towards tourism impacts. Further, the study envisages the need for engaging residents in developing a progressive and participatory planning process for future tourism activities in the area.

Social implications

The study offers critical social implications for city tourism development. It suggests a community-based approach should be adopted to sensitize residents about the positive benefits of tourism.

Originality/value

The study is a novel attempt concerning residents’ residents perceptual differences towards tourism impacts. Furthermore, this study investigated socio-cultural impacts of tourism under two separate categories for better understanding. in doing so, this study provides finer understanding of perception of residents towards tourism impacts in Indian context. The findings of the study will prove critical for different stakeholders in developing future tourism framework and policies in the region.
Sensitivity about inventory leanness
Authors: Chakrabarty Subrata , Wang Liang (Lucas)
Published: October 2020

Purpose

This study aims to suggest that firms and stock market investors are more sensitive about inventory leanness when industry information technology (IT) usage is high. First, when industry IT usage is high, a firm's inventory leanness is more responsive to information inputs (cash holding and sales efficiency). Second, when industry IT usage is high, the price-to-earnings ratio (indicative of stock market investors' willingness to pay a premium) is more sensitive to the firm's inventory leanness.

Design/methodology/approach

This study highlights the contextual role of industry IT usage during the 1998–2009 lost decade (wherein the steepest falls in manufacturing jobs happened in the USA).

Findings

The results highlight the significant contextual role of industry IT usage. In manufacturing industry sectors with high IT usage, (1) inventory levels of firms are more responsive to information inputs and (2) stock market investors have greater appreciation for inventory leanness.

Originality/value

The lost decade, 1998–2009, was a difficult period for the manufacturing industry. Nonetheless, there was variation in stock market valuations of manufacturing firms, with many firms outperforming others. Stock market investors were sensitive to inventory leanness. Firms that positively impressed stock market investors were strategically positioned in high IT usage industry sectors and prioritized inventory leanness. Further, their inventories were sensitive to information inputs – their inventories were leaner in response to improved sales-efficiency and/or shortage in cash.
Managing expectations with emotional accountability: making City Hospitals accountable during the COVID-19 pandemic in Turkey
Authors: Demirag Istemi , Fırtın Cemil Eren , Tekin Bilbil Ebru
Published: October 2020

Purpose

This paper explores the role of the COVID-19 pandemic in the financial and parliamentary accountability mechanisms of public-private partnership (PPP) “City Hospitals” in Turkey. Diverse and changing accountability mechanisms are explored regarding budgetary, affordability and emotions during the COVID-19 pandemic.

Design/methodology/approach

This is a case study of City Hospitals in Turkey. Empirical data are collected and analyzed qualitatively from publicly available government and related sources, Turkish National Audit reports (Sayistay), strategic healthcare investment plans, relevant laws, decrees and NGO reports and news articles.

Findings

Existing accountability mechanisms for arranging and/or delivering value-for-money (VfM) in Turkish PPP hospitals are weak. This provided policy makers with more flexibility to manage expectations of its citizens in dealing with COVID-19 pandemic. Political decision makers, through PPPs, created political capital for themselves by engaging in emotional accountability at the expense of better financial and parliamentary accountability.

Originality/value

This article contributes to the literature by articulating how roles of accountability change in crisis and introduces the concept of emotional accountability during a period of heavy infrastructure investments in City Hospitals in Turkey.
Understanding managerial ambidexterity: a people–situation interaction approach
Authors: Wang Ruifang , Gibbons Patrick
Published: October 2020

Purpose

It is increasingly recognised that managers play a central role in organisational ambidexterity. While some scholars have recently begun to explain the nature and antecedents of ambidextrous behaviour among managers, much remains to be learned about the micro-foundations of this behaviour. Adopting a people–situation interaction approach, this paper investigates the antecedents to managerial ambidexterity from both situational and individual difference considerations.

Design/methodology/approach

This study adopts a quantitative approach using a combination of survey and archival data from 305 managers.

Findings

The results indicate that learning goal orientation is positively related with managerial ambidexterity, whereas there is no significant relationship between functional experience breadth and managerial ambidexterity. In testing moderation effects, discretionary slack is found to positively moderate the association between learning goal orientation and ambidexterity and between functional experiences and ambidexterity.

Practical implications

This paper provides suggestions on employees selection and training, along with organisational support, in enacting managerial ambidexterity.

Originality/value

Guided by individual difference theory, this paper adds value to one’s understanding of the antecedents to managerial ambidexterity. It contributes to the ambidexterity literature from the micro-foundation perspective.
Capability development in startup and mature enterprises
Authors: Ma Hongjia , Lang Chunting , Sun Qing , Singh Deeksha
Published: October 2020

Purpose

The purpose of this study is to review the literature of enterprise capability, which comprises the three dimensions of operational, dynamic and improvisational capabilities, and analyze their differences. Through this review, the authors aim to enrich the enterprise capability theory and provide some directions for entrepreneurial practice in the face of volatility, uncertainty, complexity and ambiguity (VUCA).

Design/methodology/approach

The study is based on a systematic review of the literature on enterprise capability as it relates to entrepreneurial firms, following the content analysis approach as described in Gaur and Kumar (2018).

Findings

The authors’ conceptual model compares the capability levels of startups and mature enterprises and presents a model for the dynamic evolution of the capability levels of enterprises. In doing so, this study enriches the enterprise capability theory and lays the theoretical foundation for the follow-up empirical research. The authors also provide guidance for entrepreneurial practice in the face of VUCA.

Originality/value

In recent years, scholars have begun to explore the issue of enterprise capability in the field of entrepreneurship. However, because of different research perspectives, one lacks clarity on the concept and dimensions of enterprise capability. The capability theory is relatively weak in guiding the practice of enterprises; enterprises lack effective response strategies in a changing environment, and the failure rate of startups is high. This study aims to develop a deeper understanding of enterprise capability.
The role of network structural properties in supply chain sustainability: a systematic literature review and agenda for future research
Authors: Alinaghian Leila , Qiu Jilin , Razmdoost Kamran
Published: October 2020

Purpose

The purpose of this paper is to systematically review and assess the current status of research on supply chain sustainability from a network structural perspective and provide an organising framework for future scholarship in this area.

Design/methodology/approach

By adopting an evidence-based approach, this study conducts a systematic review of 73 articles from 18 peer-reviewed journals published between 2000 and 2020.

Findings

Adopting a social network analysis approach, the review identifies specific node-level (i.e. degree centrality, closeness centrality and betweenness centrality) and network-level (i.e. network density, network sub-groups and network diversity) structural properties that play a role in supply chain sustainability. The results reveal that structural properties determine the extent of perception of sustainability risks, the diffusion of sustainability targets, introduction of sustainable innovations, development of sustainability capabilities, adoption of sustainability initiatives and the monitoring of sustainability performance throughout the supply chain.

Originality/value

By distinguishing between supply network and sustainable supply network types, this study extends the existing understandings of the role of network connectivity patterns in supply chain sustainability through synthesising and evaluating the extant literature. This study further clarifies the role of these network structural properties in supply chain sustainability by describing their impact on a set of sustainable supply chain management practices through which firms achieve sustainability goals across their supply chains.
Theorising health professionals’ prevention and management practices with children and young people experiencing self‐harm: a qualitative hospital‐based case study
Authors: MacDonald Sarah , Sampson Catherine , Biddle Lucy , Kwak Sung Yeon , Scourfield Jonathan , Evans Rhiannon
Published: October 2020

Self‐harm in young people remains a significant concern. Studies of emergency departments have centred on negative professional attitudes. There has been limited interrogation and theorisation of what drives such attitudes, and the contexts that sustain them. Adopting a complex systems lens, this study aimed to explore how systems shape professional and patient interactions. It draws upon interviews with healthcare and affiliated professionals (n = 14) in a UK case study hospital, with primary focus on the emergency department. Data were analysed using a thematic approach and the principles of grounded theory. Four themes emerged, with the first three centralising how professionals’ practices operate within: (1) a framework of risk management; (2) expectations of progressing patients through the care pathway; and (3) a culture of specialist expertise, with resulting uncertainty about who is responsible for self‐harm. The fourth theme considers barriers to system change. A small number of participants described efforts to enact positive modifications to practices, but these were frustrated by entrenched system structures. The potential detrimental impacts for patient care and professional wellbeing are considered. Future practice needs systemic action to support professionals in treating patients experiencing self‐harm, while future research requires more ethnographic explorations of the complex system in situ.
A novel workflow to improve genotyping of multigene families in wildlife species: An experimental set‐up with a known model system
Authors: Gillingham Mark A. F. , Montero B. Karina , Wihelm Kerstin , Grudzus Kara , Sommer Simone , Santos Pablo S. C.
Published: October 2020

Genotyping complex multigene families in novel systems is particularly challenging. Target primers frequently amplify simultaneously multiple loci leading to high PCR and sequencing artefacts such as chimeras and allele amplification bias. Most genotyping pipelines have been validated in nonmodel systems whereby the real genotype is unknown and the generation of artefacts may be highly repeatable. Further hindering accurate genotyping, the relationship between artefacts and genotype complexity (i.e. number of alleles per genotype) within a PCR remains poorly described. Here, we investigated the latter by experimentally combining multiple known major histocompatibility complex (MHC) haplotypes of a model organism (chicken, Gallus gallus, 43 artificial genotypes with 2–13 alleles per amplicon). In addition to well‐defined ‘optimal’ primers, we simulated a nonmodel species situation by designing ‘cross‐species’ primers based on sequence data from closely related Galliform species. We applied a novel open‐source genotyping pipeline (ACACIA; https://gitlab.com/psc_santos/ACACIA), and compared its performance with another, previously published pipeline (AmpliSAS). Allele calling accuracy was higher when using ACACIA (98.5% versus 97% and 77.8% versus 75% for the ‘optimal’ and ‘cross‐species’ data sets, respectively). Systematic allele dropout of three alleles owing to primer mismatch in the ‘cross‐species’ data set explained high allele calling repeatability (100% when using ACACIA) despite low accuracy, demonstrating that repeatability can be misleading when evaluating genotyping workflows. Genotype complexity was positively associated with nonchimeric artefacts, chimeric artefacts (nonlinearly by levelling when amplifying more than 4–6 alleles) and allele amplification bias. Our study exemplifies and demonstrates pitfalls researchers should avoid to reliably genotype complex multigene families.
Cognitive control beliefs and cognitive functioning in mid‐ to late‐life
Authors: Raldiris Tarah L. , Perez Elliottnell , Donovan Emily K. , Dzierzewski Joseph M.
Published: October 2020

Objectives

Older adults experience age‐related cognitive declines and often feel as if the severity of these declines is out of their control. Recent research suggests, though, that control beliefs may be related to less age‐related declines. The aim of the current study was to investigate cognitive domain‐specific control beliefs and the link between those cognitive control beliefs and cognitive functioning among a nationwide sample of adults (N = 3,670), as well as to explore whether cognitive control beliefs moderated the relationship between age and cognitive functioning.

Method

The aims were addressed using data from the national Midlife in the United States study (MIDUS II). Cognitive functioning was assessed using the Brief Test of Adult Cognition by Telephone (BTACT), and cognitive control beliefs were assessed with the Personality in Intellectual Aging Contexts (PIC) Inventory Control Scales.

Results

Regression analyses revealed that adults with higher control beliefs demonstrated better cognitive functioning. Moderation analyses indicated cognitive control beliefs moderated the relationship between age and executive functioning, but not the association between age and episodic memory.

Conclusion

Results suggested that the relationship between age and executive functioning was weaker at high levels of cognitive control beliefs. Future research should establish the directionality of the effect between cognitive control beliefs and cognition and investigate the association between control beliefs and cognition in samples at higher risk for substantial cognitive decline, including the oldest‐old.
ATTRIBUTE NONATTENDANCE AND CITIZEN PREFERENCES FOR ECOSYSTEM‐BASED FISHERIES MANAGEMENT: THE CASE OF ATLANTIC MENHADEN
Authors: Harrison Jane L. , Naumenko Alexandra , Whitehead John C.
Published: October 2020

A survey revealed preferences for ecosystem‐based management of the Atlantic menhaden fishery. Survey results informed fisheries managers who consider tradeoffs between harvest levels and jobs compared to ecosystem services. Increases in commercial fishing revenue and jobs increased the probability that a respondent would vote in favor of a harvest quota increase. Increased quotas associated with lower water quality and reductions in game fish stock and shore bird populations led to a decrease in the probability of a vote for increased quotas. Accounting for stated attribute nonattendance altered the marginal rate of substitution between economic attributes and ecosystem attributes substantively. (JEL Q22, Q28, Q51)
Endobronchial ultrasound guided transbronchial cryobiopsy versus forceps biopsy in peripheral lung lesions
Authors: Torky Mohamed , Elshimy Wafaa S. , Ragab Mohamed AE. , Attia Ghada A. , Lopez Raquel , Mate Jose Luis , Centeno Carmen , Serra Pere , Tazi Mezalek Rachid , Pérez Eli Nancy , Manzano Juan Ruiz , Rosell Antonio , Andreo Felipe
Published: October 2020

Introduction

Radial probe endobronchial ultrasound (RP‐EBUS) is a modern technique for diagnosis of peripheral lung lesions. It is assumed that the addition of transbronchial cryobiopsy (TBCB) could increase the diagnostic value for RP‐EBUS.

Objectives

The main objectives were to evaluate the efficacy and safety of RP‐EBUS‐guided TBCB for diagnosis of peripheral lung lesions and comparing it with RP‐EBUS‐guided transbronchial forceps biopsy.

Methods

Sixty patients with peripheral lung diseases were divided into two groups. Group I included 45 patients who were eligible for TBCB and they subjected to forceps transbronchial biopsy (forceps TBB) and TBCB guided by RP‐EBUS. Fifteen patients who were not eligible for TBCB were included in group II and they were subjected to forceps TBB and/or cytology retrieval procedures guided by RP‐EBUS.

Results

In group I, forceps TBB had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of; 67.5%, 100%, 100%, 18.8%, and 69.8%, respectively, while TBCB had sensitivity, specificity, PPV, NPV, and accuracy of 75%, 100%, 100%, 23.1%, and 76.7%, respectively. The sensitivity in group II was 80% and the overall results including both groups were sensitivity, specificity, PPV, NPV, and accuracy of 85.2%, 100%, 100%, 42.8%, and 86.7%, respectively. Regarding the complications, only one patient (1.7%) had significant bleeding. One patient (1.7%) had pneumothorax and another patient (1.7%) suffered from hypoxemia.

Conclusions

RP‐EBUS‐guided TBCB is a safe and effective technique for diagnosis of peripheral lung lesions. TBCB has achieved higher diagnostic values and better quality of samples.
Visual function subtyping in children with early‐onset cerebral visual impairment
Authors: Sakki Hanna , Bowman Richard , Sargent Jenefer , Kukadia Roopen , Dale Naomi
Published: October 2020

Aim

To develop a data‐driven subgrouping method to identify and profile subtypes of early‐onset childhood cerebral visual impairment (CVI).

Method

Sixty‐three children with suspected or diagnosed congenital CVI were recruited (28 males, 35 females, median age=8y, range=5–16y). Cognitive, basic, and higher‐order vision functions were assessed and quality of life, functional vision questionnaire, neurodevelopmental, and ophthalmological data were collected. Cluster analysis and other statistical analyses were undertaken to determine and validate the subgrouping.

Results

Forty‐three participants completing the full test battery were included in cluster analysis, revealing two subgroups. Group A1 (n=15) showed selective visual perception and visuomotor deficits. Group A2 (n=28) showed more severe and broader visual perception and visuomotor deficits, and variable visual acuity. A third, lower‐functioning group, Group B (n=20), was differentiated and showed significant visual acuity reduction compared with Group A (p<0.001, V=0.69). External validation showed significant cooccurring ophthalmological (e.g. strabismus p<0.001, V=0.59) and motor impairment differences (χ2=16.26, p<0.001, V=0.51) between the three groups. All groups had lowered parent‐reported quality of life and everyday functional vision.

Interpretation

Statistical analyses revealed three subgroups with differentiated vision function characteristics on a gradient of severity. The subgrouping method provides the first steps in developing a novel classification system to underpin future clinical diagnostics and profiling of early‐onset CVI.

What this paper adds

Three data‐driven subgroups of vision function deficits were identified.

A similar severity gradient was shown in cooccurring cognitive and neurodevelopmental deficits.

Reported quality of life and functional vision difficulties were low across all groups.
How low can we go? Influence of sample rate on equine pelvic displacement calculated from inertial sensor data
Authors: Pfau Thilo , Reilly Patrick
Published: October 2020

Background

Low‐cost sensor devices are often limited in terms of sample rate. Based on signal periodicity, the Nyquist theorem allows determining the minimum theoretical sample rate required to adequately capture cyclical events, such as pelvic movement in trotting horses.

Objectives

To quantify the magnitude of errors arising with reduced sample rates when capturing biological signals using the example of pelvic time‐displacement series and derived minima and maxima used to quantify movement asymmetry in lame horses.

Study design

Data comparison.

Methods

Root mean square (RMS) errors between the ‘reference’ time‐displacement series, captured with a validated inertial sensor at 100 Hz sample rate, and down‐sampled time‐series (8 Hz to 50 Hz) are calculated. Accuracy and precision are determined for maxima and minima derived from the time‐displacement series.

Results

Average RMS errors are <2 mm at 50 Hz sample rate, <4 mm at 40 Hz, <7 mm between 25 and 35 Hz, and increase to up to 20 mm at 20 Hz and below. Accuracy for maxima and minima is generally below 1mm. Precision is 1 mm at 50 Hz sample rate, 3 mm at 40Hz and ≥9 mm at 20 Hz and below.

Main limitations

Only sample rate, no other sensor parameters were investigated.

Conclusions

Sample rate related errors for inertial sensor derived time‐displacement series of pelvic movement are <2mm at 50 Hz, a rate that many low‐cost loggers, smartphones or wireless sensors can sustain hence rendering these devices valid options for quantifying parameters relevant for lameness examinations in horses.
Implantable loop recorders can detect paroxysmal atrial fibrillation in Standardbred racehorses with intermittent poor performance
Authors: Buhl Rikke , Nissen Sarah D. , Winther Marie L. K. , Poulsen Sofie K. , Hopster‐Iversen Charlotte , Jespersen Thomas , Sanders Prashanthan , Carstensen Helena , Hesselkilde Eva M.
Published: October 2020

Background

Limited information is available on paroxysmal atrial fibrillation (PAF) in the horse. Indeed, undiagnosed PAF could result in poor performance. Due to the intermittent occurrence, PAF is difficult to diagnose. However, implanting a small ECG device (implantable loop recorder, ILR) subcutaneously, allows the continuous and automatic detection of PAF.

Objectives

The aim was to investigate the potential of ILRs as a tool for diagnosing PAF in horses with poor performance.

Study design

Prospective field study.

Methods

Twelve racing Standardbred trotters with intermittent reduced performance (mean age: six years) were enrolled prospectively. The ILR was implanted subcutaneously at the fifth or sixth left intercostal space and data from the ILR was collected during the study period in which the horses were followed for a median duration of 7.5 month (range 6‐28).

Results

The ILR was able to detect PAF in four out of twelve racehorses. The ILR also detected sustained atrial fibrillation (AF) in one horse during the study. The ILRs rely on RR detection and R waves were correctly identified in 96%. One hundred episodes were categorised as AF by the ILRs and subsequently visual ECG inspection categorised 12 as sinus rhythm (SR), 28 as sinus arrhythmia (SA), 14 as other arrhythmias and 46 as AF episodes. The Root Mean Square of the Successive Differences (RMSSD) values were significantly increased for AF compared to SR and SA.

Main limitations

Few horses included and duration of study period varied among the horses. Further it was not possible to assess the sensitivity of the device in the current study and the ILRs proved to have a high rate of false positive misclassifications.

Conclusions

This study indicates that ILRs can be used for detection of PAF episodes and could be a useful ECG tool for horses presenting with poor performance. This methodology provides a platform to facilitate the long‐term assessment of AF development and quantification of AF burden in horses. Further studies including both healthy and poor performing horses are needed in order to learn more about PAF prevalence in racehorses.
Stimulation of GMP formation in hGBP1 is mediated by W79 and its effect on the antiviral activity
Authors: Raninga Nikunj , Nayeem Shahid M. , Gupta Sowmiya , Mullick Ranajoy , Pandita Esha , Das Saumitra , Deep Shashank , Sau Apurba Kumar
Published: October 2020

Interferon‐inducible large GTPases are critical for innate immunity. The distinctive feature of a large GTPase, human guanylate binding protein‐1 (hGBP1), is the sequential hydrolysis of GTP into GMP via GDP. Despite several structural and biochemical studies, the underlying mechanism of assembly‐stimulated GMP formation by hGBP1 and its role in immunity are not fully clarified. Using a series of biochemical, biophysical, and in silico experiments, we studied four tryptophan residues, located near switch I‐II (in and around the active site) to understand the conformational changes near these regions and also to investigate their effect on enhanced GMP formation. The W79A mutation showed significantly reduced GMP formation, whereas the W81A and W180A substitutions exhibited only a marginal defect. The W114A mutation showed a long‐range effect of further enhanced GMP formation, which was mediated through W79. We also observed that after first phosphate cleavage, the W79‐containing region undergoes a conformational change, which is essential for stimulated GMP formation. We suggest that this conformational change helps to reposition the active site for the next cleavage step, which occurs through a stable contact between the indole moiety of W79 and the main chain carbonyl of K76. We also showed that stimulated GMP formation is crucial for antiviral activity against hepatitis C. Thus, the present study not only provides new insight for the stimulation of GMP formation in hGBP1, but also highlights the importance of the enhanced second phosphate cleavage product in the antiviral activity.
Linkage mapping evidence for a syntenic QTL associated with flowering time in perennial C4 rhizomatous grasses Miscanthus and switchgrass
Authors: Jensen Elaine , Shafiei Reza , Ma Xue‐Feng , Serba Desalegn D. , Smith Daniel P. , Slavov Gancho T. , Robson Paul , Farrar Kerrie , Thomas Jones Sian , Swaller Timothy , Flavell Richard , Clifton‐Brown John , Saha Malay C. , Donnison Iain
Published: October 2020

Flowering in perennial species is directed via complex signalling pathways that adjust to developmental regulations and environmental cues. Synchronized flowering in certain environments is a prerequisite to commercial seed production, and so the elucidation of the genetic architecture of flowering time in Miscanthus and switchgrass could aid breeding in these underdeveloped species. In this context, we assessed a mapping population in Miscanthus and two ecologically diverse switchgrass mapping populations over 3 years from planting. Multiple flowering time quantitative trait loci (QTL) were identified in both species. Remarkably, the most significant Miscanthus and switchgrass QTL proved to be syntenic, located on linkage groups 4 and 2, with logarithm of odds scores of 17.05 and 21.8 respectively. These QTL regions contained three flowering time transcription factors: Squamosa Promoter‐binding protein‐Like, MADS‐box SEPELLATA2 and gibberellin‐responsive bHLH137. The former is emerging as a key component of the age‐related flowering time pathway.
HLA genotyping meets response to immune checkpoint inhibitors prediction: A story just started
Authors: Ivanova Milena , Shivarov Velizar
Published: October 2020

The implementation of the immune checkpoint blockade as a therapeutic option in contemporary oncology is one of the significant immunological achievements in the last century. Constantly accumulating evidence suggests that the response to immune checkpoint inhibitors (ICIs) is not universal. Therefore, it is critical to identify determinants for response, resistance and adverse effects of immune checkpoint therapy that could be developed as prognostic and predictive markers. Recent large scale analyses of cancer genome data revealed the key role of HLA class I and class II molecules in cancer immunoediting, and it appears that HLA diversity can predict response to ICIs. In the present review, we summarize the emerging data on the role of HLA germline variations as a marker for response to ICIs.
Addressing the challenges of artificial intelligence in medicine
Authors: Smith Marcus , Heath Jeffery Rachael C.
Published: October 2020

The application of artificial intelligence in medicine, particularly in relation to screening and diagnosis of disease through imaging analysis, will have a profound impact over the next decade. This communication discusses regulatory challenges that should be considered by physicians and how potential issues may be mitigated using a collaborative approach, drawing on the combined expertise of relevant stakeholders.
Experience with research paradigms relates to infants’ direction of preference
Authors: Santolin Chiara , Garcia‐Castro Gonzalo , Zettersten Martin , Sebastian‐Galles Nuria , Saffran Jenny R.
Published: October 2020

Interpreting and predicting direction of preference in infant research has been a thorny issue for decades. Several factors have been proposed to account for familiarity versus novelty preferences, including age, length of exposure, and task complexity. The current study explores an additional dimension: experience with the experimental paradigm. We reanalyzed the data from 4 experiments on artificial grammar learning in 12‐month‐old infants run using the head‐turn preference procedure (HPP). Participants in these studies varied substantially in their number of laboratory visits. Results show that the number of HPP studies is related to direction of preference: Infants with limited experience with the HPP setting were more likely to show familiarity preferences than infants who had amassed more experience with this paradigm. This evidence has important implications for the interpretation of experimental results: Experience with a given method or, more broadly, with the laboratory environment may affect infants’ patterns of preferences.
Dynamic changes in numerical acuity in 4‐month‐old infants
Authors: Wang Jinjing (Jenny) , Feigenson Lisa
Published: October 2020

Preverbal infants represent the approximate numerosity of visual and auditory arrays: By 6 months old, they reliably discriminate eight dots or tones from 16 (a 1:2 ratio), but not eight from 12 (a 2:3 ratio). The precision of this approximate number sense improves gradually over childhood and into adulthood. However, less is known about numerical abilities in younger infants, and in particular, whether there is developmental change in the number sense in the first half year of life. Here, in four experiments, we measured numerical precision in 4‐month‐old infants (N = 128) using a visual habituation task comparable to that in studies of older infants. We found that 4‐month‐olds exhibited poorer numerical discrimination than the 6‐month‐olds tested in previous studies, dishabituating to a 1:4 change in numerical ratio, but not a 1:3 change. Like older infants, 4‐month‐olds’ numerical precision improved when they were provided with redundant visual and auditory input; when both visual and auditory information were present, 4‐month‐olds discriminated a 1:3 but not a 1:2 ratio. These results suggest that Approximate Number System precision develops in early infancy and may be sensitive to intersensory redundancy as early as four months of age.
Blow to the Northeast? Intraspecific differentiation of Populus davidiana suggests a north‐eastward skew of a phylogeographic break in East Asia
Authors: Song Xinya , Milne Richard I. , Fan Xiaoyan , Xie Siyu , Zhang Lei , Zheng Honglei , Fan Liqiang , Chung Jae Min , Chung Myong Gi , Ma Tao , Xu Xiaoting , Wang Jing , Mao Kangshan
Published: October 2020

Aim

There is increasing interest in the role that biological traits, and historical and biogeographic processes, play in the formation of phylogeographic patterns. An arid belt that once existed in northern China might have affected many plants, but this has yet to be tested in an arid‐tolerant, wind‐dispersed species. Here, we tested how intrinsic and extrinsic factors have affected the phylogeography of Populus davidiana.

Location

East Asia.

Methods

Genetic variation was surveyed across 40 populations (555 individuals) covering the Chinese range of P. davidiana, using 16 nuclear microsatellite loci (nSSRs) and four chloroplast fragments (cpDNA). Demographic and migration hypotheses were tested using coalescent‐based approaches, and the present and past potential distributions were predicted using species distribution modelling.

Results

Molecular data divide P. davidiana into two lineages, north‐eastern China (NECR) and central and northern China (CNCR); however, the dividing line is around 118ºE for nSSRs, but 122ºE for cpDNA. The range and habitat of the two lineages barely overlap at present, and their ecological separation may have initiated around the Pliocene‐Quaternary boundary, when major intraspecific cpDNA clades diverged. NECR and CNCR experienced post‐glacial north‐eastward and northward range shifts respectively. Bi‐directional historical gene flow was detected between NECR and CNCR for both bi‐parentally inherited nSSRs and maternally inherited cpDNA. Demographic inferences suggest a severe bottleneck for CNCR and especially NECR, around the latest Pleistocene.

Main conclusions

The phylogeographic break within P. davidiana reflects the impacts of biogeographic history, climate and biological traits. Its plumed, wind‐dispersed seeds might be especially significant because prevailing south‐western spring winds may have moved the NECR‐CNCR boundary further east than similar phylogenetic breaks in other species, and also moved the cpDNA boundary relative to that for nuclear markers. Biological traits, therefore, should also be considered when examining the genetic and ecological differentiation between closely related taxa.
The carboxy‐terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC‐activation
Authors: Dafinger Claudia , Mandel Amrei M. , Braun Alina , Göbel Heike , Burgmaier Kathrin , Massella Laura , Mastrangelo Antonio , Dötsch Jörg , Benzing Thomas , Weimbs Thomas , Schermer Bernhard , Liebau Max C.
Published: October 2020

Autosomal recessive polycystic kidney disease (ARPKD) is mainly caused by variants in the PKHD1 gene, encoding fibrocystin (FC), a large transmembrane protein of incompletely understood cellular function. Here, we show that a C‐terminal fragment of human FC can suppress a signalling module of the kinase SRC and signal transducer and activator of transcription 3 (STAT3). Consistently, we identified truncating genetic variants specifically affecting the cytoplasmic tail in ARPKD patients, found SRC and the cytoplasmic tail of fibrocystin in a joint dynamic protein complex and observed increased activation of both SRC and STAT3 in cyst‐lining renal epithelial cells of ARPKD patients.