bluuebunny/crossref_metadata_2025 huggingface dataset:
Gigapixel behavioral and neural activity imaging with a novel multi-camera array microscope
Authors: Thomson Eric E , Harfouche Mark , Konda Pavan C , Seitz Catherine , Kim Kanghyun , Cooke Colin , Xu Shiqi , Jacobs Whitney S , Blazing Robin , Chen Yang , Sharma Sunanda , Dunn Timothy W , Park Jaehee , Horstmeyer Roarke , Naumann Eva A
Published: October 2021

The dynamics of living organisms are organized across many spatial scales. However, current cost-effective imaging systems can measure only a subset of these scales at once. We have created a scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution recording from multiple spatial scales simultaneously, ranging from cellular structures to large-group behavioral dynamics. By collecting data from up to 96 cameras, we computationally generate gigapixel-scale images and movies with a field of view over hundreds of square centimeters at 5um sensitivity. This allows us to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales, including larval zebrafish, fruit flies, nematodes, carpenter ants, and slime mold. The MCAM architecture allows stereoscopic tracking of the z-position of organisms using the overlapping field of view from adjacent cameras. Further, we demonstrate the ability to acquire dual color fluorescence video of multiple freely moving zebrafish, recording neural activity via ratiometric calcium imaging. Overall, the MCAM provides a powerful platform for investigating cellular and behavioral processes across a wide range of spatial scales by removing the bottlenecks imposed by single-camera image acquisition systems.
Towards CRISPR/Cas9-based gene drive in the diamondback mothPlutella xylostella
Authors: Xu X. , Harvey-Samuel T. , Siddiqui H. , Ang J. , Anderson M.A.E , Reitmayer C. , Lovett E. , Leftwich P.T. , You M. , Alphey L.
Published: October 2021

Promising to provide powerful genetic control tools, gene drives have been constructed in multiple dipterans, yeast and mice, for the purposes of population elimination or modification. However, it remains unclear whether these techniques can be applied to lepidopterans. Here, we used endogenous regulatory elements to drive Cas9 and sgRNA expression in the diamondback moth, (Plutella xylostella), and test the first split-drive system in a lepidopteran. The diamondback moth is an economically important global agriculture pest of cruciferous crops and has developed severe resistance to various insecticides, making it a prime candidate for such novel control strategy development. A very high level of somatic editing was observed in Cas9/sgRNA transheterozygotes, although no significant homing was revealed in the subsequent generation. Although heritable, Cas9-medated germline cleavage, as well as maternal and paternal Cas9 deposition was observed, rates were far lower than for somatic cleavage events, indicating robust somatic but limited germline activity of Cas9/sgRNA under the control of selected regulatory elements. Our results provide valuable experience, paving the way for future construction of gene drive-based genetic control strategies in DBM or other lepidopterans.
AREAdata: a worldwide climate dataset averaged across spatial units at different scales through time
Authors: Smith Thomas P. , Stemkovski Michael , Koontz Austin , Pearse William D.
Published: October 2021

In an era of increasingly cross-discipline collaborative science, it is imperative to produce data resources which can be quickly and easily utilised by non-specialists. In particular, climate data often require heavy processing before they can be used for analyses. Here we describe AREAdata, a free-to-use online global climate dataset, pre-processed to provide the averages of various climate variables across differing administrative units (e.g., countries, states). These are daily estimates, based on the Copernicus Climate Data Store’s ERA-5 data, regularly updated to the near-present and provided as direct downloads from our website (https://pearselab.github.io/areadata/). The daily climate estimates from AREAdata are consistent with other openly available data, but at much finer-grained spatial and temporal scales than available elsewhere. AREAdata complements the existing suite of climate resources by providing these data in a form more readily usable by researchers unfamiliar with GIS data-processing methods, and we anticipate these resources being of particular use to environmental and epidemiological researchers.
Hematopoietic stem and progenitor cells integrate Bacteroides-derived innate immune signals to promote gut tissue repair
Authors: Hayashi Yoshikazu , Sezaki Maiko , Nakato Gaku , Biswas Subinoy , Morishima Tatsuya , Fakruddin Md , Moon Jieun , Ahn Soyeon , Kim Pilhan , Miyamoto Yuji , Baba Hideo , Fukuda Shinji , Takizawa Hitoshi
Published: October 2021

Bone marrow (BM)-resident hematopoietic stem and progenitor cells (HSPCs) are often activated by bacterial insults to replenish the host hemato-immune system, but how they integrate the associated tissue damage signals to initiate distal tissue repair is largely unknown. Here, we showed that acute gut inflammation expands HSPCs in the BM through GM-CSFR activation, and directs them to inflamed mesenteric lymph nodes for further differentiation into myeloid cells specialized in gut tissue repair. We also identified that this process is exclusively mediated by Bacteroides, a commensal gram-negative bacteria, that activates innate immune signaling. In contrast, chronic gut inflammation reduces HSC potential for hematopoietic reconstitution and immune response against infection. Similarly, microbial signals contribute to aging-associated HSPC expansion. These findings establish a cross-organ communication that promotes tissue regeneration, but if sustained, impairs tissue homeostasis that may be relevant to aging and chronic disorders.

The infiltrating microbiota Bacteroides upon acute colitis directed MPP migration from the BM to the MLN for their subsequent expansion and differentiation into tissue-repairing Ly6C+/G+ cells, whereas chronic colitis impairs HSC functionality similarly as aging.
Chlorhexidine reduced susceptibility associated to tetracycline resistance in clinical isolates of Escherichia coli
Authors: Royer Guilhem , Ortiz de la Rosa Jose-Manuel , Vuillemin Xavier , Lacombe Béatrice , Chau Françoise , Clermont Olivier , Mercier-Darty Mélanie , Decousser Jean-Winoc , Ricard Jean-Damien , Nordmann Patrice , Denamur Erick , Poirel Laurent
Published: October 2021

Chlorhexidine is a widely used antiseptic in hospital and community healthcare. Decreased susceptibility to this compound has been recently described in Klebsiella pneumoniae and Pseudomonas aeruginosa, together with cross-resistance to colistin. Surprisingly, few data are available for Escherichia coli, the main species responsible for community and healthcare-associated infections. In order to decipher chlorhexidine resistance mechanisms in E. coli, we studied both in vitro derived and clinical isolates through whole-genome sequence analysis. Comparison of strains grown in vitro under chlorhexidine pressure identified mutations in the gene mlaA coding for a phospholipid transport system. Phenotypic analyses of single-gene mutant from the Keio collection confirmed the role of this mutation in the decreased susceptibility to chlorhexidine. However, mutations in mlaA were not found in isolates from large clinical collections. In contrast, genome wide association studies (GWAS) showed that, in clinical strains, chlorhexidine reduced susceptibility was associated with the presence of tetA genes of class B coding for efflux pumps and located in a Tn10 transposon. Construction of recombinant strains in E. coli K-12 confirmed the role of tetA determinant in acquired resistance to both chlorhexidine and tetracycline. Our results reveal two different evolutionary paths leading to chlorhexidine decreased susceptibility: one restricted to in vitro evolution conditions and involving a retrograde phospholipid transport system; the other observed in clinical isolates associated with efflux pump TetA. None of these mechanisms provides cross-resistance to colistin or to the cationic surfactant octenidine. This work demonstrates the GWAS power to identify new resistance mechanisms in bacterial species.
Determination of oligomeric states of proteins via dual-color colocalization with single molecule localization microscopy
Authors: Tan Hua Leonhard , Bungert-Plümke Stefanie , Kortzak Daniel , Fahlke Christoph , Stölting Gabriel
Published: October 2021

The oligomeric state of plasma membrane proteins is the result of the interactions between individual proteins and an important determinant of their function. Most approaches used to address this question rely on extracting these complexes from their native environment, which may disrupt weaker interactions. Therefore, microscopy techniques have been increasingly used in recent years to determine oligomeric states in situ. Classical light microscopy suffers from insufficient resolution, but super-resolution methods such as single molecule localization microscopy (SMLM) can circumvent this problem. When using SMLM to determine oligomeric states of proteins, subunits are labeled with fluorescent proteins that only emit light following activation or conversion at different wavelengths. Typically, individual molecules are counted based on a binomial distribution analysis of emission events detected within the same diffraction-limited volume. This strategy requires low background noise, a high recall rate for the fluorescent tag and intensive post-imaging data processing. To overcome these limitations, we developed a new method based on SMLM to determine the oligomeric state of plasma membrane proteins. Our dual-color colocalization (DCC) approach allows for accurate in situ counting even with low efficiencies of fluorescent protein detection. In addition, it is robust in the presence of background signals and does not require temporal clustering of localizations from individual proteins within the same diffraction limited volume, which greatly simplifies data acquisition and processing. We used DCC-SMLM to resolve the controversy surrounding the oligomeric state of two SLC26 multifunctional anion exchangers and to determine the oligomeric state of four members of the SLC17 family of organic anion transporters.
TREM2+ and interstitial macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques
Authors: Upadhyay Amit A. , Hoang Timothy N. , Pino Maria , Boddapati Arun K. , Viox Elise G. , Lee Michelle Y.H. , Corry Jacqueline , Strongin Zachary , Cowan David A. , Beagle Elizabeth N. , Horton Tristan R. , Hamilton Sydney , Aoued Hadj , Harper Justin L. , Nguyen Kevin , Pellegrini Kathryn L. , Tharp Gregory K. , Piantadosi Anne , Levit Rebecca D. , Amara Rama R. , Barratt-Boyes Simon M. , Ribeiro Susan P. , Sekaly Rafick P. , Vanderford Thomas H. , Schinazi Raymond F. , Paiardini Mirko , Bosinger Steven E.
Published: October 2021

The COVID-19 pandemic remains a global health crisis, yet, the immunopathological mechanisms driving the development of severe disease remain poorly defined. Here, we utilize a rhesus macaque (RM) model of SARS-CoV-2 infection to delineate perturbations in the innate immune system during acute infection using an integrated systems analysis. We found that SARS-CoV-2 initiated a rapid infiltration (two days post infection) of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and induction of interferon-stimulated genes. At this early interval, we also observed a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generated a novel compendium of RM-specific lung macrophage gene expression using a combination of sc-RNA-Seq data and bulk RNA-Seq of purified populations under steady state conditions. Using these tools, we generated a longitudinal sc-RNA-seq dataset of airway cells in SARS-CoV-2-infected RMs. We identified that SARS-CoV-2 infection elicited a rapid recruitment of two subsets of macrophages into the airway: a C206+MRC1-population resembling murine interstitial macrophages, and a TREM2+ population consistent with CCR2+ infiltrating monocytes, into the alveolar space. These subsets were the predominant source of inflammatory cytokines, accounting for ~75% of IL6 and TNF production, and >90% of IL10 production, whereas the contribution of CD206+MRC+ alveolar macrophages was significantly lower. Treatment of SARS-CoV-2 infected RMs with baricitinib (Olumiant®), a novel JAK1/2 inhibitor that recently received Emergency Use Authorization for the treatment of hospitalized COVID-19 patients, was remarkably effective in eliminating the influx of infiltrating, non-alveolar macrophages in the alveolar space, with a concomitant reduction of inflammatory cytokines. This study has delineated the major subsets of lung macrophages driving inflammatory and anti-inflammatory cytokine production within the alveolar space during SARS-CoV-2 infection.

One sentence summary

Multi-omic analyses of hyperacute SARS-CoV-2 infection in rhesus macaques identified two population of infiltrating macrophages, as the primary orchestrators of inflammation in the lower airway that can be successfully treated with baricitinib
Tales of schizomid tails: patterns in schizomid flagellum shape from elliptical Fourier analysis
Authors: Kallal Robert J. , de Miranda Gustavo Silva , Garcia Erika L. , Wood Hannah M.
Published: October 2021

The arachnid order Schizomida is a relatively understudied group of soil-dwelling predators found on all continents except Antarctica. While efforts to understand their biology are growing, there is still much to know about them. A curious aspect of their morphology is the male flagellum, a sexually dimorphic, tail-like structure which differs in shape across the order and functions in their courtship rituals. The flagellar shape is important for taxonomic classification, yet few efforts have been made to examine shape diversity across the group. Using elliptical Fourier analysis, a type of geometric morphometrics based on outline shape, we quantified shape differences across a combined nearly 550 outlines in the dorsal and lateral views, categorizing them based on genus, family, biogeographic realm, and habitat, with special emphasis on Caribbean and Cuban fauna. We tested for allometric relationships, differences in disparity based on locations and sizes in morphospace among these categories, and for clusters of shapes in morphospace. We found multiple differences in all categories despite apparent overlaps in morphospace, evolutionary allometry, and evidence for discrete clusters in some flagellum shapes. This study can serve as a foundation for further study on the evolution, diversification, and taxonomic utility of the male flagellum.
Topological properties accurately predict cell division events and organization of Arabidopsis thaliana’s shoot apical meristem
Authors: Matz Timon W. , Wang Yang , Kulshreshtha Ritika , Sampathkumar Arun , Nikoloski Zoran
Published: October 2021

Cell division and the resulting changes to the cell organization affect the shape and functionality of all tissues. Thus, understanding the determinants of the tissue-wide changes imposed by cell division is a key question in developmental biology. Here, we use a network representation of live cell imaging data from shoot apical meristems (SAMs) in Arabidopsis thaliana to predict cell division events and their consequences at a tissue level. We show that a classifier based on the SAM network properties is predictive of cell division events, with validation accuracy of 82%, on par with that based on cell size alone. Further, we demonstrate that the combination of topological and biological properties, including: cell size, perimeter, distance, and shared cell wall between cells, can further boost the prediction accuracy of resulting changes in topology triggered by cell division. Using our classifiers, we demonstrate the importance of microtubule mediated cell-to-cell growth coordination in influencing tissue-level topology. Altogether, the results from our network-based analysis demonstrates a feedback mechanism between tissue topology and cell division in A. thaliana’s SAMs.

Summary statement

we use a network representation of live cell imaging data from SAMs in Arabidopsis thaliana to predict cell division events and their consequences at a tissue level.
The membrane-proximal domain of the periplasmic adapter protein plays a role in vetting substrates utilising channels 1 and 2 of RND efflux transporters
Authors: Alav Ilyas , Bavro Vassiliy N. , Blair Jessica M. A.
Published: October 2021

Active efflux by resistance-nodulation-division (RND) efflux pumps is a major contributor to antibiotic resistance in clinically relevant Gram-negative bacteria. Tripartite RND pumps, such as AcrAB-TolC ofSalmonella entericaserovar Typhimurium, comprise of an inner membrane RND transporter, a periplasmic adaptor protein (PAP) and an outer membrane factor. Previously, we elucidated binding sites within the PAP AcrA (termed binding boxes) that were important for AcrB-transporter recognition. Here, we have refined the binding box model by identifying the most critical residues involved in PAP-RND binding and show that the corresponding RND-binding residues in the closely related PAP AcrE are also important for AcrB interactions. In addition, our analysis identified a membrane-proximal domain (MPD)-residue in AcrA (K366), that when mutated, differentially affects transport of substrates utilising different AcrB efflux-channels, namely channels 1 and 2, supporting a potential role for the PAP in sensing the substrate-occupied state of the proximal binding pocket (PBP) of the transporter and substrate vetting. Our model predicts that there is a close interplay between the MPD of the PAP and the RND transporter in the productive export of substrates utilising the PBP.

Importance

Antibiotic resistance greatly threatens our ability to treat infectious diseases. In Gram-negative bacteria, overexpression of tripartite efflux pumps, such as AcrAB-TolC, contributes to multidrug resistance because they export many different classes of antibiotics. The AcrAB-TolC pump is made up of three components: the periplasmic adaptor protein (PAP) AcrA, the RND-transporter AcrB, and the outer-membrane factor TolC. Here, we identified critical residues of AcrA that are important for its function with AcrB inSalmonella entericaserovar Typhimurium. Also, we show that AcrA shares these critical residues with AcrE, a closely related PAP, explaining their interoperability with AcrB. Importantly, we identified a residue in the membrane-proximal domain of AcrA that when mutated affected how different substrates access AcrB and impacted downstream effluxviaTolC channel. Understanding the role that PAPs play in the assembly and function of tripartite RND pumps can guide novel ways to inhibit their function to combat antibiotic resistance.
Assessing microbial growth monitoring methods for challenging strains and cultures
Authors: Brown Damon , Turner Raymond J.
Published: October 2021

This is a paper focusing on the comparison of growth curves using field relevant testing methods and moving away from colony counts. Challenges exist to explore antimicrobial growth of fastidious strains, poorly culturable bacterial and bacterial communities of environmental interest. Thus, various approaches have been explored to follow bacteria growth that can be an efficient surrogate for classical optical density or colony forming unit measurements.

Here we tested optical density, ATP assays, DNA concentrations and 16S rRNA qPCR as means to monitor pure culture growth of six different species including Acetobacterium woodii, Bacillus subtilis, Desulfovibrio vulgaris, Geoalkalibacter subterraneus, Pseudomonas putida and Thauera aromatica. Optical density is and excellent, rapid monitoring method of pure culture planktonic cells but cannot be applied to environmental or complex samples. ATP assays provide rapid results but conversions to cell counts may be misleading for different species. DNA concentration is a very reliable technique which can be used for any sample type and provides genetic materials for downstream applications. qPCR of the 16S rRNA gene is a widely applicable technique for monitoring microbial cell concentrations but is susceptible to variation between replicates. DNA concentrations were found to correlate the best with the other three assays and provides the advantages of rapid extraction, consistency between replicates and potential for downstream analysis, DNA concentrations is determined to be the best universal monitoring method for complex environmental samples.
A cell-free assay for rapid screening of inhibitors of hACE2-receptor - SARS-CoV-2-Spike binding
Authors: Kikuchi Nanami , Willinger Or , Granik Naor , Navon Noa , Ackerman Shanny , Samuel Ella , Antman Tomer , Katz Noa , Goldberg Sarah , Amit Roee
Published: October 2021

We present a cell-free assay for rapid screening of candidate inhibitors of protein binding, focusing on inhibition of the interaction between the SARS-CoV-2 Spike receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2). The assay has two components: fluorescent polystyrene particles covalently coated with RBD, termed virion-particles (v-particles), and fluorescently-labeled hACE2 (hACE2F) that binds the v-particles. When incubated with an inhibitor, v-particle - hACE2F binding is diminished, resulting in a reduction in the fluorescent signal of bound hACE2F relative to the non-inhibitor control, which can be measured via flow cytometry or fluorescence microscopy. We determine the amount of RBD needed for v-particle preparation, v-particle incubation time with hACE2F, hACE2F detection limit, and specificity of v-particle binding to hACE2F. We measure the dose response of the v-particles to a known inhibitor. Finally, we demonstrate that RNA-hACE2F granules trap v-particles effectively, providing a basis for potential RNA-hACE2F therapeutics.
Social media influencer marketing: the moderating role of materialism
Authors: Koay Kian Yeik , Cheung Man Lai , Soh Patrick Chin-Hooi , Teoh Chai Wen
Published: October 2021

Purpose

Social media influencers (SMIs) have become an important source of influence that affects consumer behaviours in their decision-making processes. As such, this justifies scholarly attention in understanding how SMIs transfer their meanings to endorsed brands and drive consumers’ positive behavioural intentions. With the intention to fill this knowledge gap, this paper aims to examine the impact of SMIs’ credibility, as manifested by trustworthiness, attractiveness and expertise, along with the moderating effects of materialism, on followers’ purchase intention.

Design/methodology/approach

Self-administrated online surveys were used to collect data from Instagram users. A total of 191 usable data were collected and analysed using partial least square structural equation modelling.

Findings

The results show that SMIs’ trustworthiness and expertise are significant predictors of followers’ purchase intention. Moreover, the moderating effect of materialism on the relationship between attractiveness and purchase intention is significant. Notably, the influence of attractiveness on purchase intention is greater when materialism is high.

Originality/value

This research contributes to the SMI literature by examining the influence of SMIs’ trustworthiness, attractiveness and expertise, along with the moderating effect of materialism, on followers’ purchase intention.
Future public policy guidelines for the sustainable development of Guaviare, Colombia for the year 2035
Authors: Camarena José Luis , Osorio Vera Francisco Javier , Rojas Jimenez Hector Heraldo , Borda Medina Ernesto , Esteban Torregroza Juan Camilo , Tabares-Valencia Jesús David
Published: October 2021

Purpose

This paper aims to propose future public policy guidelines (FPPG) in sustainable regional development for Guaviare (Colombia) – a territory affected by environmental and social distress – for the year 2035.

Design/methodology/approach

Following collective action theory and sustainable regional development literature, a foresight exercise was conducted using site focus groups and semi-structured interviews with local participants to identify future strategic change drivers and the most relevant social actors for the attainment of economic, social and environmental development in the Guaviare through FPPG.

Findings

The findings suggest that the development of public policies regarding building consensus around Guaviare’s economic, environmental and social issues, reducing conflict between the region’s cultural and environmental ways, decreasing isolation from the centers of decision-making, increasing the transparency of public institutions and reducing insecurity to attract investments are all crucial to attaining sustainable regional development.

Originality/value

Interdisciplinarity is implicit in the local perspectives on the problem that impedes sustainable development in San José del Guaviare. The paper’s main contribution is the long-term vision that breaks away from the traditional short-termism in public policy guidelines in a Latin American context. Methodologically, the significant contribution is the convergent alignment of specific foresight methods toward public policy guidelines’ analysis and design processes.
An analogy between analytical, approximate and numerical methods in nonlinear buckling of functionally graded columns
Authors: Salmalian Kaveh , Alijani Ali , Ramezannejad Azarboni Habib
Published: October 2021

Purpose

The purpose of this study is to investigate the post-buckling analysis of functionally graded columns by using three analytical, approximate and numerical methods. A pre-defined function as an initial assumption for the post-buckling path is introduced to solve the differential equation. The finite difference method is used to approximate the lateral deflection of the column based on the differential equation. Moreover, the finite element method is used to derive the tangent stiffness matrix of the column.

Design/methodology/approach

The non-linear buckling analysis of functionally graded materials is carried out by using three analytical, finite difference and finite element methods. The elastic deformation and Euler-Bernoulli beam theory are considered to establish the constitutive and kinematics relations, respectively. The governing differential equation of the post-buckling problem is derived through the energy method and the calculus variation.

Findings

An incremental iterative solution and the perturbation of the displacement vector at the critical buckling point are performed to determine the post-buckling path. The convergence of the finite element results and the effects of geometric and material characteristics on the post-buckling path are investigated.

Originality/value

The key point of the research is to compare three methods and to detect error sources by considering the derivation process of relations. This comparison shows that a non-incremental solution in the analytical and finite difference methods and an initial assumption in the analytical method lead to an error in results. However, the post-buckling path in the finite element method is traced by the updated tangent stiffness matrix in each load step without any initial limitation.
Lessons learned from the impact of COVID-19 on the global construction industry
Authors: Ogunnusi Mercy , Omotayo Temitope , Hamma-Adama Mansur , Awuzie Bankole Osita , Egbelakin Temitope
Published: October 2021

Purpose

The construction industry represents most of every country’s finances and vital to continued economic growth and activities, especially in developing countries. The impact of the severe acute respiratory syndrome-2 disease (COVID19) on the government’s income resulted in the expectation of many public projects being cancelled or delayed providing little opportunity for the emergence of new public projects. This study collated a global qualitative perspective (survey interviews) on the lessons learned during the COVID-19 pandemic and the positive and negative impacts for future-proofing the construction sector.

Design/methodology/approach

In total, 76 respondents from five continents excluding South America responded to the online open-ended structured questionnaire. Data collected were analysed through artificial inteligence analytics tool – Zoho analytics.

Findings

The themes indicating the positive impact obtained from the interview were overhead cost reduction, remote working environment, focus on health and safety, improved productivity and sustainability goals while the themes signifying the negative impact were low business turnover, delays in construction payment and output, difficulties working from home and job losses. Supply chain management, construction project management improvement, concentration on health and safety and effective virtual working environment were collated as themes on lessons learned.

Social implications

The major findings of this study emphasise on the need to improve the occupational health and safety and onsite safety measures for future proofing of the construction industry.

Originality/value

The findings from the analyses made clear the imperativeness of the built environment research, with a focus on novel framework and strategies for future proofing the construction industry.
“I didn’t want to be a troublemaker” – doctoral students’ experiences of change in supervisory arrangements
Authors: Schmidt Manuela , Hansson Erika
Published: October 2021

Purpose

During the lengthy process of PhD studies, supervisory changes commonly occur for several different reasons, but their most frequent trigger is a poor supervisory relationship. Even though a change in supervisors is a formal bureaucratic process and not least the students’ rights, in practice it can be experienced as challenging. Therefore, the purpose of this study is to explore how doctoral students experience a change in supervisory arrangements.

Design/methodology/approach

This study highlights the voices of 19 doctoral students who experienced at least one supervisory change during their doctoral studies.

Findings

The findings were structured chronologically, revealing the students’ experiences prior, during and after the changes. In total, 12 main themes were identified. Most of the interviewed students experienced the long decision-making processes as stressful, difficult and exhausting, sometimes causing a lack of mental well-being. However, once the change was complete, they felt renewed, energized and capable of continuing with their studies. It was common to go through more than one change in supervisory arrangements. Further, the students described both the advantages of making a change yet also the long-lasting consequences of this change that could affect them long after they had completed their PhD programs.

Originality/value

The study fulfills an identified need to investigate the understudied perspective of doctoral students in the context of change in supervisory arrangements. A change in the academic culture is needed to make any changes in supervisory arrangements more acceptable thus making PhD studies more sustainable.
Effect of NPC1L1 polymorphism on warfarin stable dose in Chinese patients under heart valve replacement surgery
Authors: Ma Siqing , Luo Zhiying , Zhou Xinmin , Zhou Honghao , Chen Ling , Zhang Wei
Published: October 2021

Warfarin is the most often anticoagulant choice for preventable thromboembolism. Notably, vitamin K plays a vital role in the process of warfarin's anticoagulant effect. Therefore, we presume NPC1L1, a key transporter of vitamin K (VK) intestinal absorption, may modulate the anticoagulant effect of warfarin. Studies have shown that NPC1L1(‐762T>C, rs2073548) and p53 (P72R, rs1042522) variations are implicated in influencing NPC1L1 expression. This study aimed to assess the association between these two variants and warfarin stable dose (WSD). A two‐stage extreme phenotype design was used to explore the influence of these two variants (rs2073548, rs1042522) on WSD variance in 655 Chinese patients undergoing heart valve replacement surgery. NPC1L1 rs2073548, p53 rs1042522, VKORC1 rs9923231 and CYP2C9*1/*3 polymorphisms were genotyped by polymerase chain reaction‐restriction fragment polymorphism (PCR‐RFLP) or Sanger sequencing, respectively. WSD was identified when target monitoring international normalized ratio (INR) value at 2.0‐3.0. In the discovery phase, NPC1L1 rs2073548 A allele carriers occupied a significantly higher rate in the low dose group (P = .019). However, in the validation group, warfarin dosage in patients with the rs2073548 AA, AG and GG genotypes were 2.91 ± 0.97 mg/day, 3.02 ± 1.00 mg/day and 3.00 ± 1.06 mg/day, respectively. Multiple linear regression analysis results suggested that CYP2C9*3 and VKORC1 rs9923231, but not NPC1L1 rs2073548, were independent predictors of WSD in Chinese heart valve replacement (HVR) surgical patients.
In defense of Direct Care: Limiting access to military hospitals could worsen quality and safety
Authors: Zogg Cheryl K. , Lichtman Judith H. , Dalton Michael K. , Learn Peter A. , Schoenfeld Andrew J. , Perez Koehlmoos Tracey , Weissman Joel S. , Cooper Zara
Published: October 2021

Objective

Ongoing health care reforms within the US Military Health System (MHS) are expected to shift >1.9 million MHS beneficiaries from military treatment facilities (MTFs) into local civilian hospitals over the next 1–2 years. The objective of this study was to examine how such health care reforms are likely to affect the quality of MHS care.

Data sources

Adult MHS beneficiaries, aged 18–64 years, treated in MTFs (under a program known as Direct Care) were compared against (1) MHS beneficiaries treated in locally available civilian hospitals (under a program known as Purchased Care) and (2) similarly‐aged adult civilian patients across the United States. MHS beneficiaries in Direct and Purchased Care were identified from fiscal‐year 2016–2018 MHS inpatient claims. National inpatients were identified in the 2017 Nationwide Readmissions Database.

Study design

Retrospective cohort.

Data collection

Differences in quality were compared using two sets of quality metrics endorsed by the US Agency for Healthcare Research and Quality (AHRQ): Inpatient Quality Indicators, 19 quality metrics that look at differences in in‐hospital mortality, and Patient Safety Indicators, 18 quality metrics that look at differences in in‐hospital morbidity and adverse events. Among MHS beneficiaries (Direct and Purchased Care), we further simulated what changes in quality indicators might look like under various proposed scenarios of reduced access to Direct Care.

Principal findings

A total of 502,252 MHS admissions from 37 MTFs and surrounding civilian hospitals were included (326,076 Direct Care, 179,176 Purchased Care). Nationwide, 9.34 million adult admissions from 2453 hospitals were included. On average, MHS beneficiaries treated in MTFs experienced better inpatient quality and improved patient safety compared with MHS beneficiaries treated in locally available civilian hospitals (e.g., summary observed‐to‐expected ratio for medical mortality: 0.98 vs. 1.03, p < 0.001) and adult patients across the United States (0.98 vs. 1.02, p < 0.001). Simulations of proposed changes resulted in consistently worse outcomes for MHS patients, whether reducing MTF access by 10%, 20%, or 50% nationwide; limiting MTF access to active‐duty beneficiaries; or closing MTFs with the worst performance on patient safety (p < 0.001 for overall quality indicators for each).

Conclusions

Reducing access to MTFs could result in significant harm to MHS patients. The results underscore the importance of health‐policy planning based on evidence‐based evaluation and the need to consider the consequential downstream effects caused by changes in access to care.
Multispecies site occupancy modelling and study design for spatially replicated environmental DNA metabarcoding
Authors: Fukaya Keiichi , Kondo Natsuko Ito , Matsuzaki Shin‐ichiro S. , Kadoya Taku
Published: October 2021

Environmental DNA (eDNA) metabarcoding has become widely applied to gauge biodiversity in a non‐invasive and cost‐efficient manner. The detection of species using eDNA metabarcoding is, however, imperfect owing to various factors that can cause false negatives in the inherent multistage workflow. Imperfect detection in the multistage workflow of eDNA metabarcoding also raises an issue of study design, namely, how available resources should be allocated among the different stages to optimize survey efficiency.

Here, we propose a variant of the multispecies site occupancy model for eDNA metabarcoding studies where samples are collected at multiple sites within a region of interest. Unlike traditional site occupancy models that deal with binary detection data, this model describes the variation in sequence reads, the output of the high‐throughput sequencers. It explicitly accounts for the hierarchical workflow of eDNA metabarcoding and interspecific heterogeneity and allows the analysis of the sources of variation in the detectability of species throughout the different stages of the workflow. We also introduced a Bayesian decision analysis framework to identify the study design that optimizes the effectiveness of species detection with a limited budget.

An application of the model to freshwater fish communities in the Lake Kasumigaura watershed, in Japan, highlighted a remarkable inhomogeneity in the detectability of species, indicating a potential risk of the biased detection of specific species. Species with lower site occupancy probabilities tended to be difficult to detect as they had lower capture probabilities and fewer sequence reads. The expected abundance of sequence reads was predicted to vary by up to 23.5 times among species. An analysis of the study design suggested that ensuring multiple within‐site replications of the environmental samples is preferred to achieve higher species detection effectiveness, provided that tens of thousands of sequence reads were secured per replicate.

The proposed framework makes the application of eDNA metabarcoding more error‐tolerant, allowing ecologists to monitor ecological communities more efficiently.
Impact of single‐stage laparoscopic trans‐cystic exploration on hospital procedures, admissions and length‐of‐stay in common bile duct stone clearance
Authors: Vu Anh N. , Eskander Jacqueline , Chan Steven T. F. , Houli Nezor , Bui Hai T.
Published: October 2021

Background

Single‐stage approach with bile duct exploration is considered the most efficient and cost‐effective method of bile duct clearance. In Australia, apart from centres with subspecialty interests, notably in Brisbane, Queensland, a multi‐stage approach with endoscopic retrograde cholangiopancreatography (ERCP) is used more frequently. We aim to evaluate the impact of single stage laparoscopic trans‐cystic exploration (LTCE) versus multi‐stage approach for choledocholithiasis.

Methods

This was a retrospective cohort study. Medicare Benefits Schedule codings were used to identify patients who had the following procedures between December 2011 and December 2019: laparoscopic cholecystectomy (LC) and ERCP, LC and LTCE, LC and LTCE and ERCP. Primary outcomes were number of hospital procedures, admissions and additive length of stay (aLOS), the cumulative hospital stay from admission to discharge.

Results

Of 607 patients, 204 (34%) patients received a single‐stage LTCE, while 403 (66%) patients had a multi‐stage approach. In the LTCE group, 82% (168) patients and 93% (190) patients had one procedure and one admission respectively for stone clearance (P = 0.001). The median aLOS was 4 days for LTCE versus 7 days for multi‐stage approach (P = 0.001; 95% CI for difference − 3 to −2). In the multi‐stage group, 16% (65) patients had three or more procedures and 49% (199) patients required two or more hospital admissions to achieve stone clearance.

Conclusion

LTCE for stone clearance can be successfully accomplished with reductions in hospital admissions, number of procedures and length of stay. This has further economic and health resource implications.
Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma
Authors: Li Jie , Zhao Yu‐Hang , Tian Su‐Fang , Xu Cheng‐Shi , Cai Yu‐Xiang , Li Kai , Cheng Yan‐Bing , Wang Ze‐Fen , Li Zhi‐Qiang
Published: October 2021

Aims

Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post‐radiochemotherapy.

Methods

Somatic mutation profile in GBM and SGS was examined using whole‐genome sequencing and deep‐whole‐exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis.

Results

A mutation cluster containing two founding mutations in tumor‐suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating‐agents – exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy.

Conclusions

Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.
Can a Robot Lie? Exploring the Folk Concept of Lying as Applied to Artificial Agents
Authors: Kneer Markus
Published: October 2021

The potential capacity for robots to deceive has received considerable attention recently. Many papers explore the technical possibility for a robot to engage in deception for beneficial purposes (e.g., in education or health). In this short experimental paper, I focus on a more paradigmatic case: robot lying (lying being the textbook example of deception) for nonbeneficial purposes as judged from the human point of view. More precisely, I present an empirical experiment that investigates the following three questions: (a) Are ordinary people willing to ascribe deceptive intentions to artificial agents? (b) Are they as willing to judge a robot lie as a lie as they would be when human agents engage in verbal deception? (c) Do people blame a lying artificial agent to the same extent as a lying human agent? The response to all three questions is a resounding yes. This, I argue, implies that robot deception and its normative consequences deserve considerably more attention than they presently receive.
Language Processing Differences Between Blind and Sighted Individuals and the Abstract Versus Concrete Concept Difference
Authors: Canessa Enrique , Chaigneau Sergio E. , Moreno Sebastián
Published: October 2021

In the property listing task (PLT), participants are asked to list properties for a concept (e.g., for the concept dog, “barks,” and “is a pet” may be produced). In conceptual property norming (CPNs) studies, participants are asked to list properties for large sets of concepts. Here, we use a mathematical model of the property listing process to explore two longstanding issues: characterizing the difference between concrete and abstract concepts, and characterizing semantic knowledge in the blind versus sighted population. When we apply our mathematical model to a large CPN reporting properties listed by sighted and blind participants, the model uncovers significant differences between concrete and abstract concepts. Though we also find that blind individuals show many of the same processing differences between abstract and concrete concepts found in sighted individuals, our model shows that those differences are noticeably less pronounced than in sighted individuals. We discuss our results vis‐a‐vis theories attempting to characterize abstract concepts.
Discerning Mouse Trajectory Features With the Drift Diffusion Model
Authors: Leontyev Anton , Yamauchi Takashi
Published: October 2021

Mouse tracking, a new action‐based measure of behavior, has advanced theories of decision making with the notion that cognitive and social decision making is fundamentally dynamic. Implicit in this theory is that people's decision strategies, such as discounting delayed rewards, are stable over task design and that mouse trajectory features correspond to specific segments of decision making. By applying the hierarchical drift diffusion model and the Bayesian delay discounting model, we tested these assumptions. Specifically, we investigated the extent to which the “mouse‐tracking” design of decision‐making tasks (delay discounting task, DDT and stop‐signal task, SST) deviate from the standard “keypress” design of decision making tasks. We found remarkable agreement in delay discounting rates (intertemporal impatience) obtained in the keypress and mouse‐tracking versions of DDT (ρ = 0.90) even though these tasks were given about 1 week apart. Rates of evidence accumulation converged well in the two versions (DDT, ρ = .86; SST, ρ = .55). Omission/commission error in SST showed high agreement (ρ = .42, ρ = .53). Mouse‐motion features such as maximum velocity and AUC (area under the curve) correlated well with nondecision time (ρ = −.42) and boundary separation (ρ = .44)—the amount of information needed to accumulate prior to making a response. These results indicate that the response time (RT) and motion‐based decision tasks converge well at a fundamental level, and that mouse‐tracking features such as AUC and maximum velocity do indicate the degree of decision conflict and impulsivity.
Anti‐thymocyte globulin and post‐transplant cyclophosphamide predisposes to inferior outcome when using cryopreserved stem cell grafts
Authors: Novitzky‐Basso Igor , Remberger Mats , Chen Carol , Pasić Ivan , Lam Wilson , Law Arjun , Gerbitz Armin , Viswabandya Auro , Lipton Jeffrey H. , Kim Dennis D. , Kumar Rajat , Mattsson Jonas , Michelis Fotios V.
Published: October 2021

During 2020, the concurrent novel COVID‐19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft‐versus‐host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched‐related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post‐HSCT, possibly due to the combination of ATG and post‐transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.