bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast and compact matching statistics analytics
Authors: Cunial Fabio , Denas Olgert , Belazzougui Djamal
Published: October 2021

Motivation

Fast, lightweight methods for comparing the sequence of ever larger assembled genomes from ever growing databases are increasingly needed in the era of accurate long reads and pan-genome initiatives. Matching statistics is a popular method for computing whole-genome phylogenies and for detecting structural rearrangements between two genomes, since it is amenable to fast implementations that require a minimal setup of data structures. However, current implementations use a single core, take too much memory to represent the result, and do not provide efficient ways to analyze the output in order to explore local similarities between the sequences.

Results

We develop practical tools for computing matching statistics between large-scale strings, and for analyzing its values, faster and using less memory than the state of the art. Specifically, we design a parallel algorithm for shared-memory machines that computes matching statistics 30 times faster with 48 cores in the cases that are most difficult to parallelize. We design a lossy compression scheme that shrinks the matching statistics array to a bitvector that takes from 0.8 to 0.2 bits per character, depending on the dataset and on the value of a threshold, and that achieves 0.04 bits per character in some variants. And we provide efficient implementations of range-maximum and range-sum queries that take a few tens of milliseconds while operating on our compact representations, and that allow computing key local statistics about the similarity between two strings. Our toolkit makes construction, storage, and analysis of matching statistics arrays practical for multiple pairs of the largest genomes available today, possibly enabling new applications in comparative genomics.

Availability ad implementation

Our C/C++ code is available at https://github.com/odenas/indexed_ms under GPL-3.0.
A model for the intrinsic limit of cancer therapy: duality of treatment-induced cell death and treatment-induced stemness
Authors: Angelini Erin , Wang Yue , Zhou Joseph X. , Qian Hong , Huang Sui
Published: October 2021

Abstract

Intratumor cellular heterogeneity and non-genetic cell plasticity in tumors pose a recently recognized challenge to cancer treatment. Because of the dispersion of initial cell states within a clonal tumor cell population, a perturbation imparted by a cytocidal drug only kills a fraction of cells. Due to dynamic instability of cellular states the cells not killed are pushed by the treatment into a variety of functional states, including a “stem-like state” that confers resistance to treatment and regenerative capacity. This immanent stress-induced stemness competes against cell death in response to the same perturbation and may explain the near-inevitable recurrence after any treatment. This double-edged-sword mechanism of treatment complements the selection of preexisting resistant cells in explaining post-treatment progression. Unlike selection, the induction of a resistant state has not been systematically analyzed as an immanent cause of relapse. Here, we present a generic elementary model and analytical examination of this intrinsic limitation to therapy. We show how the relative proclivity towards cell death versus transition into a stem-like state, as a function of drug dose, establishes either a window of opportunity for containing tumors or the inevitability of progression following therapy. The model considers measurable cell behaviors independent of specific molecular pathways and provides a new theoretical framework for optimizing therapy dosing and scheduling as cancer treatment paradigms move from “maximal tolerated dose,” which may promote therapy induced-stemness, to repeated “minimally effective doses” (as in adaptive therapies), which contain the tumor and avoid therapy-induced progression.
Silencing XIST on the future active X: Searching human and bovine preimplantation embryos for the repressor
Authors: Aksit Melis A , Yu Bo , Roelen Bernard AJ , Migeon Barbara R.
Published: October 2021

X inactivation is the means of equalizing the dosage of X chromosomal genes in male and female eutherian mammals, so that only one X is active in each cell. The XIST locus (in cis) on each additional X chromosome initiates the transcriptional silencing of that chromosome, making it an inactive X. How the active X in both males and females is protected from inactivation by its own XIST locus is not well understood in any mammal. Previous studies of autosomal duplications suggest that gene(s) on the short arm of human chromosome 19 repress XIST function on the active X. Here, we examine the time of transcription of some candidate genes in preimplantation embryos using single-cell RNA sequencing data from human embryos and qRT-PCR from bovine embryos. The candidate genes assayed are those transcribed from 19p13.3-13.2, which are widely expressed and can remodel chromatin. Our results confirm that XIST is expressed at low levels from the future active X in embryos of both sexes; they also show that the XIST locus is repressed in both sexes when pluripotency factors are being upregulated, during the 4-8 cell and morula stages in human and bovine embryos – well before the early blastocyst (E5) when XIST on the inactive X in females begins to be upregulated. Our data suggest a role for DNMT1, UHRF1, SAFB and SAFB2 in XIST repression; they also exclude XACT and other 19p candidate genes and provide the transcriptional timing for some genes not previously assayed in human or bovine preimplantation embryos.
Choose carefully, act quickly: Efficient decision making with selective inhibition in attractor neural networks
Authors: Liu Belle , Lo Chung-Chuan , Wu Kuo-An
Published: October 2021

The ability to decide swiftly and accurately in an urgent scenario is crucial for an organism’s survival. The neural mechanisms underlying the perceptual decision and trade-off between speed and accuracy have been extensively studied in the past few decades. Among several theoretical models, the attractor neural network model has successfully captured both behavioral and neuronal data observed in many decision experiments. However, a recent experimental study revealed additional details that were not considered in the original attractor model. In particular, the study shows that the inhibitory neurons in the posterior parietal cortex of mice are as selective to decision making results as the excitatory neurons, whereas the previous attractor model assumes the inhibitory neurons to be unselective. In this study, we investigate the attractor model with selective inhibition (selective model), which can be considered as a general case of the previous attractor model (unselective model). Our model reproduces several behavioral and neurophysiological observations. To analyze the dynamics of the selective model, we reduce it and show that selectivity adds a time-varying component to the energy landscape. This time dependence of the energy landscape allows the selective model to integrate information carefully in initial stages, then quickly converge to an attractor once the choice is clear. This results in the selective model having a more efficient speed-accuracy trade-off that is unreachable by unselective models.
Engineered endosymbionts capable of directing mammalian cell gene expression
Authors: Madsen Cody S. , Makela Ashley V. , Greeson Emily M. , Hardy Jonathan W. , Contag Christopher H.
Published: October 2021

Modular methods for directing mammalian gene expression would enable advances in tissue regeneration, enhance cell-based therapeutics and improve modulation of immune responses. To address this challenge, engineered endosymbionts (EES) that escape endosomal destruction, reside in the cytoplasm of mammalian cells, and secrete proteins that are transported to the nucleus to control host cell gene expression were developed. Microscopy confirmed that EES escape phagosomes, replicate within the cytoplasm, and can secrete reporter proteins into the cytoplasm that were then transported to the nucleus. Synthetic operons encoding the mammalian transcription factors,Stat-1andKlf6orKlf4andGata-3were recombined into the EES genome. Using controlled induction, these EES were shown to direct gene expression in J774A.1 macrophage/monocyte cells and modulate the host cell fates. Expressing mammalian transcription factors from engineered intracellular bacteria as endosymbionts comprises a new tool for directing host cell gene expression for therapeutic and research purposes.

Graphical abstract
Immunodominant and neutralizing linear B cell epitopes spanning the spike and membrane proteins of Porcine Epidemic Diarrhea Virus
Authors: Polyiam Kanokporn , Ruengjitchatchawalya Marasri , Mekvichitsaeng Phenjun , Kaeoket Kampon , Hoonsuwan Tawatchai , Joiphaeng Pichai , Roshorm Yaowaluck Maprang
Published: October 2021

Porcine Epidemic Diarrhea Virus (PEDV) is the causative agent of PED, an enteric disease that causes high mortality rates in piglets. PEDV is an alphacoronavirus that has high genetic diversity. Insights into neutralizing B cell epitopes of all genetically diverse PEDV strains are of importance, particularly for designing a vaccine that can provide broad protection against PEDV. In this work, we aimed to explore the landscape of linear B cell epitopes on the spike (S) and membrane (M) proteins of global PEDV strains. All amino acid sequences of the PEDV S and M proteins were retrieved from the NCBI database and grouped. Immunoinformatics-based methods were next developed and used to identify putative linear B cell epitopes from 14 and 5 consensus sequences generated from distinct groups of the S and M proteins, respectively. ELISA testing predicted peptides with PEDV-positive sera revealed 9 novel immunodominant epitopes on the S protein. Importantly, 7 of these novel immunodominant epitopes and other subdominant epitopes were demonstrated to be neutralizing epitopes by neutralization-inhibition assay. Additionally, our study shows the first time that M protein is also the target of neutralizing antibodies as 7 neutralizing epitopes in the M protein were identified. Conservancy analysis revealed that epitopes in the S1 subunit are more variable than those in the S2 subunit and M protein. In this study, we offer the immunoinformatics approach for linear B cell epitope identification and a more complete profile of linear B cell epitopes across the PEDV S and M proteins, which may contribute to the development of a greater PEDV vaccine as well as peptide-based immunoassays.
A gender-bias-mitigated, data-driven precision medicine system to assist in the selection of biological treatments of grade 3 and 4 knee osteoarthritis: development and preliminary validation of precisionKNEE
Authors: Heidari Nima , Parkin James , Olgiati Stefano , Meloni Davide , Fish Brady , Noorani Ali , Slevin Mark , Azamfirei Leonard
Published: October 2021

Introduction

Osteoarthritis is a leading cause of global disability and is set to worsen with the concurrent rise in rates of obesity and an ageing population [1]. Current clinical solutions are sub-optimal with regards to their invasiveness and outcomes. Orthopaedic biologics is an emerging field that offers alternative and parallel treatment options to address this problem. Determining which patients will benefit most from these novel treatments is key in developing clinical pathways.

Methods

Our dataset included 329 patients treated with microfragmented fat injection (MFAT) over a 2 year period. Clinico-demographic data was recorded as well as 1-year Oxford Knee Score (OKS). The data was modelled to predict OKS 1-year response using Random Forest Regressors. Gender-bias was mitigated and outliers were hidden from the training model. The model was validated on raw test data and on a subset of patients with Kellgren-Lawrence grade 3 and 4 radiological evidence of arthritis, age greater than 64, preoperative OKS less than or equal to 27 and idiopathic aetiology of arthritis.

Results

The mean age and mean body mass index (BMI) of patients in our dataset was 66.4 years, 26.9 respectively. 53.5% of patients had Kellgren-Lawrence grade 4 arthritis.

The final models RMSE was 6.72, MAE was 5.38 and r-squared was 0.23 on raw test data. An RMSE of 9.77 and MAE of 7.81 was achieved when validating the model on our subset of patients. Wilcoxon signed rank tests found no evidence of predicted results being statistically significantly different to ground truth values (p ¿ 0.05).

Preoperative OKS and Kellgren-Lawrence arthritis grade was the most important feature in our model.

Discussion

Our model is performant and able to predict 1 year OKS response outcome within our set of patients. We have found key features of prediction and would recommend these are researched further to improve model performance.

Our dataset does not compare outcomes with other standard treatments. We also don’t compare outcomes with other biologic treatments.

Ultimately, this research can be used as a tool to benefit both patients and clinicians in a combined decision-making process.
Neutralizing antibodies against SARS-CoV-2 variants of concern elicited by the Comirnaty® COVID-19 vaccine in nursing home residents
Authors: Sánchez-Sendra Beatriz , Albert Eliseo , Zulaica Joao , Torres Ignacio , Giménez Estela , Botija Pilar , Beltrán María José , Rodado Celia , Geller Ron , Navarro David
Published: October 2021

Immunosenescence may impact the functionality and breadth of vaccine-elicited humoral immune responses. The ability of sera to neutralize the SARS-CoV-2 spike protein (S) from Beta, Gamma, Delta, and Epsilon variants of concern (VOCs) relative to the ancestral Wuhan-Hu-1 strain was compared in Comirnaty® COVID-19-vaccinated elderly nursing home residents (n=30) or younger individuals (n=18) and non-vaccinated individuals who recovered from severe COVID-19 (n=19). In all groups, some participants lacked NtAb against one or more VOCs, mainly the Beta variant (15-20%). Serum NtAb titers were lowest against the Beta variant followed by Gamma, Epsilon, and Delta variants. Fold change reduction in NtAb titers relative to the ancestral strain was greatest for the Beta variant (6.7-18.8) followed by Gamma (3.6-6.2), Epsilon (2.9-5.8), and Delta (3.5-4.3) variants, regardless of the study group considered. In summary, older age, frailty, and concurrence of co-morbidities had no impact on the serum NtAb activity profile against SARS-CoV-2 VOCs.
A clinical trial to evaluate the dayzz smartphone app on employee sleep, health, and productivity at a large US employer
Authors: Robbins Rebecca , Weaver Matthew D. , Quan Stuart F. , Sullivan Jason P. , Cohen-Zion Mairav , Glasner Laura , Qadri Salim , Czeisler Charles A. , Barger Laura
Published: October 2021

Sleep deficiency is a hidden cost of our 24-7 society, with 70% of adults in the US admitting that they routinely obtain insufficient sleep. Further, it is estimated that 50-70 million adults in the US have a sleep disorder. Undiagnosed and untreated sleep disorders are associated with diminished health for the individual and increased costs for the employer. Research has shown that adverse impacts on employees and employers can be mitigated through sleep health education and sleep disorder screening and treatment programs. Smartphone applications (app) are increasingly commonplace and represent promising, scalable modalities for such programs. The dayzz app is a personalized sleep training program that incorporates assessment of sleep disorders and offers a personalized comprehensive sleep improvement solution. Using a sample of day workers affiliated with a large institution of higher education, we will conduct a single-site, parallel-group, randomized, waitlist control trial. Participants will be randomly assigned to either use the dayzz app throughout the study or receive the dayzz app at the end of the study. We will collect data on feasibility and acceptability of the dayzz app; employee sleep, including sleep behavioral changes, sleep duration, regularity, and quality; employee presenteeism, absenteeism, and performance; employee mood; adverse and safety outcomes; and healthcare utilization on a monthly basis throughout the study, as well as collect more granular daily data from the employee during pre-specified intervals. Our results will illuminate whether a personalized smartphone app is a viable approach for improving employee sleep, health, and productivity.
ToKSA - Tokenized Key Sentence Annotation - a Novel Method for Rapid Approximation of Ground Truth for Natural Language Processing
Authors: Fairfield Cameron J , Cambridge William A , Cullen Lydia , Drake Thomas M , Knight Stephen R , Masson Neil , Mills Nicholas L , Pius Riinu , Shaw Catherine A , Wu Honghan , Wigmore Stephen J , Spiliopoulou Athina , Harrison Ewen M
Published: October 2021

Objective

Identifying phenotypes and pathology from free text is an essential task for clinical work and research. Natural language processing (NLP) is a key tool for processing free text at scale. Developing and validating NLP models requires labelled data. Labels are generated through time-consuming and repetitive manual annotation and are hard to obtain for sensitive clinical data. The objective of this paper is to describe a novel approach for annotating radiology reports.

Materials and Methods

We implemented tokenized key sentence-specific annotation (ToKSA) for annotating clinical data. We demonstrate ToKSA using 180,050 abdominal ultrasound reports with labels generated for symptom status, gallstone status and cholecystectomy status. Firstly, individual sentences are grouped together into a term-frequency matrix. Annotation of key (i.e. the most frequently occurring) sentences is then used to generate labels for multiple reports simultaneously. We compared ToKSA-derived labels to those generated by annotating full reports. We used ToKSA-derived labels to train a document classifier using convolutional neural networks. We compared performance of the classifier to a separate classifier trained on labels based on the full reports.

Results

By annotating only 2,000 frequent sentences, we were able to generate labels for symptom status for 70,000 reports (accuracy 98.4%), gallstone status for 85,177 reports (accuracy 99.2%) and cholecystectomy status for 85,177 reports (accuracy 100%). The accuracy of the document classifier trained on ToKSA labels was similar (0.1-1.1% more accurate) to the document classifier trained on full report labels.

Conclusion

ToKSA offers an accurate and efficient method for annotating free text clinical data.
Functional analysis of a common BAG3 allele associated with protection from heart failure
Authors: Perez-Bermejo Juan A , Judge Luke M , Jensen Christina L , Wu Kenneth , Truong Annie , Ho Jaclyn J , Carter Matthew , Runyon Wendy V , Kaake Robyn M , Pulido Ernst , Watry Hannah L , Mandegar Mohammad A , Swaney Danielle L , So Po-Lin , Krogan Nevan J , Conklin Bruce R
Published: October 2021

Multiple genetic association studies have correlated a common allelic block linked to the BAG3 gene with a decreased incidence of heart failure, but the molecular mechanism for such protection remains elusive. One of the variants in this allele block is coding, changing cysteine to arginine at position 151 of BAG3 (rs2234962-BAG3C151R). Here, we use induced pluripotent stem cells (iPSC) to test if the BAG3C151Rvariant alters protein and cellular function in human cardiac myocytes. Quantitative protein interaction network analysis identified specific changes in BAG3C151Rprotein interaction partners in cardiomyocytes but not in iPSCs or an immortalized cell line. Knockdown of BAG3 interacting factors in cardiomyocytes followed by myofibrillar analysis revealed that BAG3C151Rassociates more strongly with proteins involved in the maintenance of myofibrillar integrity. Finally, we demonstrate that cardiomyocytes expressing the BAG3C151Rvariant have improved response to proteotoxic stress in an allele dose-dependent manner. This study suggests that the BAG3C151Rvariant increases cardiomyocyte protection from stress by enhancing the recruitment of factors critical to the maintenance of myofibril integrity, hinting that this variant could be responsible for the cardioprotective effect of the haplotype block. By revealing specific changes in preferential binding partners of the BAG3C151Rprotein variant, we also identify potential targets for the development of novel cardioprotective therapies.
A genetic screen identifies a protective type III interferon response toCryptosporidiumthat requires TLR3 dependent recognition
Authors: Gibson Alexis R. , Sateriale Adam , Dumaine Jennifer E. , Engiles Julie B. , Gullicksrud Jodi A. , O’Dea Keenan , Doench John G. , Beiting Daniel P. , Hunter Christopher A. , Striepen Boris
Published: October 2021

Cryptosporidiumis a leading cause of severe diarrhea and diarrheal-related death in children worldwide. As an obligate intracellular parasite,Cryptosporidiumrelies on intestinal epithelial cells to provide a niche for its growth and survival, but little is known about the contributions that the infected cell makes to this relationship. Here we conducted a genome wide CRISPR/Cas9 knockout screen to discover host genes required forCryptosporidium parvuminfection and/or host cell survival. Gene enrichment analysis indicated that the host interferon response, glycosaminoglycan (GAG) and glycosylphosphatidylinositol (GPI) anchor biosynthesis are important determinants of susceptibility toC. parvuminfection. Several of these pathways are linked to parasite attachment and invasion and C-type lectins on the surface of the parasite. Evaluation of transcript and protein induction of innate interferons revealed a pronounced type III interferon response toCryptosporidiumin human cells as well as in mice. Treatment of mice with IFNλ reduced infection burden and protected immunocompromised mice from severe outcomes including death, with effects that required STAT1 signaling in the enterocyte. Initiation of this type III interferon response was dependent on sustained intracellular growth and mediated by the pattern recognition receptor TLR3. We conclude that host cell intrinsic recognition ofCryptosporidiumresults in IFNλ production critical to early protection against this infection.

Author Summary

Cryptosporidiuminfection is an important contributor to global childhood mortality. There are currently no vaccines available, and the only drug has limited efficacy in immunocompromised individuals and malnourished children who need it most. To discover which host proteins are essential forCryptosporidiuminfection, we conducted a genome wide knockout screen in human host cells. Our results confirm the importance of glycosaminoglycans on the surface of epithelial cells for attachment and invasion of the parasite. We also found that host GPI anchor biosynthesis and interferon signaling pathways were enriched by our screen. Examining the role of interferon signaling further we found a type III interferon response, IFNλ, was generated in response to infection and shown to be initiated in the infected cell. Utilizing mouse models of infection, we found that the type III interferon response was important early during infection with its induction likely preceding IFNγ, a key cytokine for the control of this infection. We also determined that TLR3 was the pattern recognition receptor responsible for IFNλ production duringCryptosporidiuminfection. Our work shows that IFNλ acts directly on the enterocyte and its use in treating immunocompromised mice produced striking reductions in infection.
The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast
Authors: Yu Houqing , Kamber Roarke A , Denic Vladimir
Published: October 2021

Autophagy receptor (or adaptor) proteins facilitate lysosomal destruction of various organelles in response to cellular stress, including nutrient deprivation. To what extent membrane-resident autophagy receptors also respond to organelle-restricted cues to induce selective autophagy remains poorly understood. We find that latent activation of the yeast pexophagy receptor Atg36 by the casein kinase Hrr25 in rich media is repressed by the ATPase activity of Pex1/6, the catalytic subunits of the exportomer AAA+ transmembrane complex enabling protein import into peroxisomes. Quantitative proteomics of purified Pex3, an obligate Atg36 co-receptor, support a model in which exportomer represses Atg36 without assistance from additional membrane factors. Indeed, we reconstitute inhibition of Atg36 phosphorylation in vitro using soluble Pex1/6 and define an N-terminal unstructured region of Atg36 that enables regulation by binding to Pex1. Our findings uncover a mechanism by which a compartment-specific AAA+ complex mediating organelle biogenesis and protein quality control staves off induction of selective autophagy.
Major transcriptomic, epigenetic and metabolic changes underly the pluripotency continuum in rabbit preimplantation embryos
Authors: Bouchereau Wilhelm , Jouneau Luc , Archilla Catherine , Aksoy Irène , Moulin Anais , Daniel Nathalie , Peynot Nathalie , Calderari Sophie , Joly Thierry , Godet Murielle , Jaszczyszyn Yan , Pratlong Marine , Severac Dany , Savatier Pierre , Duranthon Véronique , Afanassieff Marielle , Beaujean Nathalie
Published: October 2021

Despite the growing interest in the rabbit model for developmental and stem cell biology, the characterization of embryos at the molecular level is still poorly documented. We conducted a transcriptome analysis of rabbit pre-implantation embryos from E2.7 (morula stage) to E6.6 (early primitive streak stage) using bulk and single-cell RNA-sequencing. In parallel, we studied oxidative phosphorylation and glycolysis and analysed active and repressive epigenetic modifications during blastocyst formation and expansion. We generated a transcriptomic, epigenetic, and metabolic map of the pluripotency continuum in rabbit preimplantation embryos and identified novel markers of naive pluripotency that might be instrumental for deriving naive pluripotent stem cell lines. Although the rabbit is evolutionarily closer to mice than to primates, we found that the transcriptome of rabbit epiblast cells shares common features with that of humans and non-human primates.

Summary Statement

Rabbit preimplantation embryos share characteristics with human and monkey embryos with respect to timing of early lineage segregation and expression of marker genes for naive and primed pluripotency.
The potential of CYP2D6 phenotyping to improve opioid dosing strategies
Authors: Cassidy Ridley , Main Ewan
Published: October 2021

Background

Prescription opioids account for more than 40% of opioid induced mortalities. With the trend towards increased opioid prescribing set to continue rising, opioid-based adverse drug reactions, (ADRs) and their associated human and financial cost present a major global public health concern. The review examined the relationship between CYP2D6 phenotypes and opioid metabolising. The aim was to establish whether screening for CYP2D6 phenotypes would improve existing opioid dosing strategies and reduce ADRs.

Method

A systematic review was conducted using the online Web of Science database. Selected key words and Boolean operator combinations were used to search the relevant literature. Identified studies were screened against pre-defined inclusion/exclusion criteria. Eligible studies were subject to full review and quality assessment. A narrative analysis was performed to synthesise data from the studies included in the final review.

Results

The review yielded five studies that met the eligibility criteria and were subject to full review. Four of the five studies reported significant effects of CYP2D6 phenotypes on opioid metabolising or opioid based ADRs. Three studies focused exclusively on pharmacokinetics, two studies focused exclusively on ADRs, and one study considered pharmacokinetics and ADRs. All pharmacokinetic studies reported a significant association between CYP2D6 phenotypes and opioid metabolising. Only one of the studies reported a significant association between CYP2D6 phenotypes and ADRs.

Conclusion

The majority of evidence considered in the review supports the role of CYP2D6 in the metabolising of opioids and opioid based ADRs. Consequently, CYP2D6 screening should be considered as a potential mechanism for improving existing opioid dosing strategies and reducing ADRs. There is a need for further higher quality primary data studies focusing specifically on CYP2D6 phenotyping in the context of dosage strategies and exploring impact in longitudinal designs. Future studies should also seek to develop cost effective CYP2D6 screening methods to help support the clinical significance of CYP2D6 phenotyping.
Exposing racial bias in midwifery education: A content analysis of images and text in Myles Textbook for Midwives
Authors: Harkness Mairi , Wallace Chlorice
Published: October 2021

Objective

To determine how people of different races and skin colours are represented within Myles Textbook for Midwives and whether the identified content is clinically relevant to people of all skin colours.

Design

Content analysis of text and images in Myles Textbook for Midwives 17th Edition, 2020

Findings

The images overwhelmingly depict light skinned people of White European appearance. When people of colour are shown they are more likely to be positioned in prominent imagery without specific link to the chapter topic. Descriptions of skin colour in the context of clinical assessment and/or treatment often applied mostly or solely to people with light colour skin. This included text referring to serious conditions or situations associated with severe morbidity or mortality.

Key conclusions

Myles Textbook for Midwives presents a light skinned White European norm and often fails to include information that is clinically relevant to the assessment and treatment of people with darker skin colours. This may lead to disparity in midwifery education and contribute to poorer outcomes for women and babies.

Implications for practice

Concrete efforts are required to identify and root out racial bias at all levels of midwifery education. This needs to happen alongside addressing current lack of good quality evidence required to support practice.
scatterHatch: an R/Bioconductor package for generating colorblind-friendly scatter plots for single-cell data
Authors: Guha Tejas , Fertig Elana , Deshpande Atul
Published: October 2021

Reduced-dimension or spatial in situ scatter plots are widely employed in bioinformatics papers analyzing single-cell data to present phenomena or cell-conditions of interest in cell groups. When displaying these cell groups, color is frequently the only graphical cue used to differentiate them. However, as the complexity of the information presented in these visualizations increases, the usefulness of color as the only visual cue declines, especially for the sizable readership with color-vision deficiencies (CVDs). In this paper, we present scatterHatch, an R package that creates easily interpretable scatter plots by redundant coding of cell groups using colors as well as patterns. We give examples to demonstrate how the scatterHatch plots are more accessible than simple scatter plots when simulated for various types of CVDs.
The Endosomal pH Regulator NHE9 is a Driver of Stemness in Glioblastoma
Authors: Ko Myungjun , Makena Monish R. , Schiapparelli Paula , Suarez-Meade Paola , Mekile Allatah X. , Lal Bachchu , Lopez-Bertoni Hernando , Laterra John , Quiñones-Hinojosa Alfredo , Rao Rajini
Published: October 2021

A small population of self-renewing stem cells initiate tumors and maintain therapeutic resistance in glioblastoma. Given the limited treatment options and dismal prognosis for this disease there is urgent need to identify drivers of stem cells that could be druggable targets. Previous work showed that the endosomal pH regulator NHE9 is upregulated in glioblastoma and correlates with worse survival prognosis. Here, we probed for aberrant signaling pathways in patient-derived glioblastoma cells and found that NHE9 increases cell surface expression and phosphorylation of multiple receptor tyrosine kinases by promoting their escape from lysosomal degradation. Downstream of NHE9-mediated receptor activation, oncogenic signaling pathways converged on the JAK2-STAT3 transduction axis to induce pluripotency genes Oct4 and Nanog and suppress markers of glial differentiation. We used both genetic and chemical approaches to query the role of endosomal pH in glioblastoma phenotypes. Loss-of-function mutations in NHE9 that failed to alkalinize endosomal lumen did not increase self-renewal capacity of gliomaspheres in vitro. However, monensin, a chemical mimetic of Na+/H+ exchanger activity, and the H+ pump inhibitor bafilomycin bypassed NHE9 to directly alkalinize the endosomal lumen resulting in stabilization of receptor tyrosine kinases and induction of Oct4 and Nanog. Using orthotopic models of primary glioblastoma cells we found that NHE9 increased tumor initiation in vivo. We propose that NHE9 initiates inside-out signaling from the endosomal lumen, distinct from the established effects of cytoplasmic and extracellular pH on tumorigenesis. Endosomal pH may be an attractive therapeutic target that diminishes stemness in glioblastoma, agnostic of specific receptor subtype.

Significance

A well-known hallmark of cancer is excessive acidification of tumor microenvironment, caused by upregulation of Na+/H+ exchanger activity on the cancer cell membrane. However, the role of organellar pH in tumor biology has not been established. This study identifies a mechanistic link between upregulation of the endosomal Na+/H+ exchanger NHE9 and stemness properties in glioblastoma, the most malignant and common brain tumor in adults. By increasing pH of the recycling endosome, NHE9 exerts a broad effect on post-translational stability and activation of multiple receptor tyrosine kinases, leading to increased stem cell-like properties of self-renewal and tumor initiation in glioblastoma models. Our findings suggest that targeting NHE9 or endosomal pH could be an effective strategy for receptor agnostic glioblastoma treatment.
ZFP423 controls EBF2 coactivator recruitment and PPARγ occupancy to determine the thermogenic plasticity of adipocytes
Authors: Shao Mengle , Zhang Qianbin , Truong Ashley , Shan Bo , Vishvanath Lavanya , Li Lin , Seale Patrick , Gupta Rana K.
Published: October 2021

Energy-storing white adipocytes maintain their identity by suppressing the energy-burning thermogenic gene program of brown and beige adipocytes. Here, we reveal that the protein–protein interaction between the transcriptional coregulator ZFP423 and brown fat determination factor EBF2 is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423–EBF2 protein interaction through CRISPR–Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, ZFP423 recruits the NuRD corepressor complex to EBF2-bound thermogenic gene enhancers. Loss of adipocyte Zfp423 induces an EBF2 NuRD-to-BAF coregulator switch and a shift in PPARγ occupancy to thermogenic genes. This shift in PPARγ occupancy increases the antidiabetic efficacy of the PPARγ agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 coactivator recruitment and PPARγ occupancy to determine the thermogenic plasticity of adipocytes and highlight the potential of therapeutically targeting transcriptional brakes to induce beige adipocyte biogenesis in obesity.
A practical method for determining film thickness using X-ray absorption spectroscopy in total electron yield mode
Authors: Isomura Noritake , Oh-ishi Keiichiro , Takahashi Naoko , Kosaka Satoru
Published: October 2021

Thin films formed on surfaces have a large impact on the properties of materials and devices. In this study, a method is proposed using X-ray absorption spectroscopy to derive the film thickness of a thin film formed on a substrate using the spectral separation and logarithmic equation, which is a modified version of the formula used in electron spectroscopy. In the equation, the decay length in X-ray absorption spectroscopy is longer than in electron spectroscopy due to a cascade of inelastic scattering of electrons generated in a solid. The modification factor, representing a multiple of the decay length, was experimentally determined using oxidized Si and Cu with films of thickness 19 nm and 39 nm, respectively. The validity of the proposed method was verified, and the results indicated that the method can be used in the analysis of various materials with thin films.
Exploiting bullets: international business and the dynamics of war
Authors: Owens Martin David
Published: October 2021

Purpose

The purpose of this paper is to critically review the existing research on the intersection between war and international business (IB) and to map out a future research agenda.

Design/methodology/approach

Drawing on corporate examples and extant literature within IB, political science and international relations, the paper provides an introduction to the main concepts of war, a review of the IB research on war and provides a critical future research agenda.

Findings

The review of the multiple strands of war-related research in IB generally reveals an understudied area. Among other biases, prior research has focused on inter-state wars and has relatively unexplored foreign direct investment (FDI) and non-FDI within civil wars. Furthermore, previous studies offer little attention to how IB and multinational companies contribute to the emergence and development of wars.

Originality/value

The paper develops an analytical and critical research agenda for future research to examine the relationship between war and IB. This includes a set of questions for each of the three major phases of war: pre-conflict, armed violence and post-conflict. To the best of my knowledge, this has not been done before in the context of IB research.
“If only…”: customer counterfactual thinking in failed recovery
Authors: Tran Hai-Anh , Strizhakova Yuliya , Liu Hongfei , Golgeci Ismail
Published: October 2021

Purpose

This paper aims to examine counterfactual thinking as a key mediator of the effects of failed recovery (vs. failed delivery) on negative electronic word-of-mouth (eWOM). The authors further investigate the effectiveness of using recovery co-creation in minimizing customers’ counterfactual thinking.

Design/methodology/approach

This research includes textual analysis of online reviews (Study 1) and three scenario-based experiments (Studies 2, 3a and 3b). In addition to using item-response scales, the authors analyze negative online reviews and participants’ open-ended responses to capture their counterfactual thinking.

Findings

Failed recovery (vs failed delivery) increases counterfactual thinking, which, in turn, increases negative eWOM. These mediating effects of counterfactual thinking are consistent across textual analyses and experimental studies, as well as across different measures of counterfactual thinking. Counterfactual thinking also impacts customer anger in experiments; however, anger alone does not explain the effects of failed recovery on negative eWOM. Counterfactual thinking can be minimized by co-created recovery, especially when it is used proactively.

Practical implications

The findings demonstrate the detrimental effects of counterfactual thinking and offer managerial insights into co-creation as a strategy to minimize customers’ counterfactual thinking. The authors also highlight the importance and ways of tracking counterfactual thinking in digital outlets.

Originality/value

The authors contribute to counterfactual thinking and service recovery research by demonstrating the effects of failed recovery on counterfactual thinking that, in turn, impacts negative eWOM and offering a novel way to measure its expression in online narratives. The authors provide guidance on how to use co-creation in the service recovery process to minimize counterfactual thinking.
Research on influencing factors of information diffusion in online social networks under different themes
Authors: Zhang Ling , Li De , Boncella Robert J.
Published: October 2021

Purpose

This paper aims to study the factors influencing online social network (OSN) information diffusion under different themes helps to understand information diffusion in general.

Design/methodology/approach

This study collects data from the Web of Science, use the strategic consulting intelligent support system for word frequency analysis and use keyword clustering to classify themes, then research information themes as influencing factors of OSN information diffusion.

Findings

Five themes of “natural disaster”, “political event”, “product marketing”, “sport and entertainment” and “health-disease” have been identified. It is found that the research objects, research methods and research theories used by scholars under different themes have different focuses, and the factors affecting information diffusion are different.

Research limitations/implications

The limitation of this paper is that it only focuses on five typical themes, and there may be more themes.

Practical implications

The research helps other scholars to conduct in-depth research on the diffusion of OSN information under different topics and focus on the content of the research on OSN information diffusion under different topics.

Social implications

The research helps other scholars to conduct in-depth research on the diffusion of social network information under different topics, so as to better understand and predict the law of information diffusion.

Originality/value

The research summarizes the research on information diffusion in OSNs from the theme level and analyses the key points and theories and further enriches the research system on information diffusion in OSNs.
Sensing and seizing in the apparel industry: the role of dynamic capabilities in fostering sustainable strategic orientations
Authors: Chevrollier Nicolas , Kuijf Fons
Published: October 2021

Purpose

This paper aims to explore how the dynamic capabilities sensing and seizing could support a sustainable (either instrumental or stewardship) strategic orientation in the apparel industry.

Design/methodology/approach

Through qualitative and inductive research design, ten companies from the Sustainable Apparel Coalition, specifically focusing on brands, were researched. Employees in strategic positions were interviewed. Subsequently, thematic analysis was realized to extract findings from both instrumental and stewardship organizations.

Findings

Instrumental organizations focus on increasing their brand, mainly by following market demands. They sense opportunities via a hierarchical organizational structure that allows for incremental innovation based on internal competition. Stewardship organizations believe in a collective approach toward conducting business effectively. While building a “sustainable case for business”, a stewardship-oriented company senses by involving their stakeholders and seeks unorthodox opportunities using a long-term internal compass as a beacon for decision-making.

Originality/value

Key capabilities are revealed that allow businesses and managers to reach higher levels of sustainability in a specific sector: the apparel industry. Especially the capabilities of stewardship-oriented companies and its ambidexterity provide a fertile base for future research at the nexus of organization development and sustainability.
High-performance work systems and burnout: the moderating role of mindset and the need for achievement
Authors: Agarwal Promila
Published: October 2021

Purpose

Drawing from the conservation of resources (COR) theory, this paper aims to examine the interaction among high-performance work systems (HPWS), growth mindset and need for achievement to explain burnout among employees.

Design/methodology/approach

The authors used SPSS PROCESS to test the research model on a sample of 341 employees from the manufacturing sector. The authors followed random sampling process to select organizations and employees within the organization.

Findings

The findings reveal a positive relationship between HPWS and job burnout. The study also confirms the interactive effect of HPWS, growth mindset and the need for achievement on burnout.

Research limitations/implications

The study explains the boundary conditions of HPWS and resolves the discrepancy associated with the negative effect of HPWS on employees. The results both confirm and expand the COR theory.

Originality/value

This is the first study to reveal the role of individual characteristics in understanding the positive relationship between HPWS and burnout. The study points out that the belief system and how need for achievement influence resource conservation strategies.
Charting research on international luxury marketing: where are we now and where should we go next?
Authors: Veloutsou Cleopatra , Christodoulides George , Guzmán Francisco
Published: October 2021

Purpose

Despite luxury's increasing globalization and broadening scope via digitalization and new markets, the intellectual structure of the overall research corpus remains tenuous. This work therefore aims to provide an overview of published work on international luxury marketing and to contribute to a better understanding of the research area.

Design/methodology/approach

Using a systematic approach, 1151 items (papers) were retrieved and 181 selected from the international luxury marketing field published before 2019. These items were analyzed by using various bibliometric techniques to identify the most productive countries, journals, influential authors, papers and research clusters.

Findings

Although most of the outputs originate from business, management and marketing journals, other disciplines also research this topic. The analysis reveals an emerging field, with 85% of the published papers appearing between 2010 and 2018, which are primarily the output of US- and UK-based authors and none of whom dominates the field. The three identified keyword clusters are (1) consumers and consumption (2) tools and (3) core themes.

Practical implications

This article contributes to our understanding of the evolution, current status and research trends of published research on international luxury marketing by presenting a mapping analysis and proposing future research directions.

Originality/value

This is the first bibliometric mapping analysis of research on the topic from its conception to 2019. It contributes insights from different research disciplines, adds to the categorization of the international luxury marketing literature and provides promising future research directions in terms of research areas and strategies.
The effect of audit committee characteristics on forward-looking disclosure
Authors: Rifai Mohamad , Siregar Sylvia Veronica
Published: October 2021

Purpose

This study aims to examine the effect of the audit committee characteristics on forward-looking disclosure.

Design/methodology/approach

The characteristics of audit committee that examined are audit committee expertise, audit committee meeting frequency and audit committee size. To measure the extent of forward-looking disclosure, this study did content analysis using a checklist of 22 forward-looking items. The samples of this research are 285 non-financial firms listed on the Indonesia Stock Exchange in the year 2015. Ordinary least square regression is used for hypotheses testing.

Findings

The results of this study show that the audit committee accounting expertise, audit committee financial expertise, the frequency of audit committee meetings and the size of the audit committee have a significant positive effect on the forward-looking disclosure.

Originality/value

To the best of the authors’ knowledge, this is the first study examining the audit committee characteristics on forward-looking disclosure in the context of Indonesia, one of the emerging markets.