bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced monitoring of healthcare shower water in augmented and non-augmented care wards showing persistence of Pseudomonas aeruginosa despite remediation work
Authors: Yetiş Özge , Ali Shanom , Karia Kush , Bassett Paul , Wilson Peter
Published: May 2023

Introduction.

Pseudomonas aeruginosa

in healthcare shower waters presents a high risk of infection to immune-suppressed patients; identifying the colonization-status of water outlets is essential in preventing acquisition.

Hypothesis/Gap Statement. Testing frequencies may be insufficient to capture presence/absence of contamination in healthcare waters between sampling and remediation activities. Standardization of outlets may facilitate the management and control of

P. aeruginosa

.

Aim. This study aims to monitor shower waters and drains for

P. aeruginosa

in augmented and non-augmented healthcare settings every 2 weeks for a period of 7 months during remedial actions.

Methodology. All shower facilities were standardized to include antimicrobial silver-impregnated showerhead/hose units, hose-length fixed to 0.8 m and replaced every 3 months. Standard hospital manual decontamination/disinfection occurred daily. Thermostatic-mixer-valves (TMVs) were replaced and disinfected if standard remediation unsuccessful.

Results. Of 560 shower and drain samples collected over 14 time-points covering 7 months,

P. aeruginosa

colonized 40 %(4/10; non-augmented) and 80 %(8/10; augmented-care) showers in the first week. For each week elapsed, new outlets became contaminated with

P. aeruginosa

by 18–19 % (P<0.001) in shower waters (OR=1.19; CI=1.09–1.31) and drains (OR=1.18; CI=1.09–1.30).

P. aeruginosa

occurrence in shower water was associated with subsequent colonization of the corresponding drain and vice versa (chi-square; P<0.001) with simultaneous contamination present in 31 %(87/280) of areas. TMV replacement was ineffective in eradicating colonisation in ~83 % of a subset (6/20; three per ward) of contaminated showers.

Conclusions. We demonstrate the difficulties in eradicating

P. aeruginosa

from hospital plumbing, particularly when contamination is no longer sporadic. Non-augmented care settings are reservoirs of

P. aeruginosa

and should not be overlooked in outbreak investigations. Antimicrobial-impregnated materials may be ineffective once colonization with

P. aeruginosa

is established beyond the hose and head. Reducing hose-length insufficient to prevent cross-contamination from shower drains.

P. aeruginosa

colonization can be transient in both drain and shower hose/head. Frequent microbiological monitoring suggests testing frequencies following HTM04-01 guidelines are insufficient to capture the colonization-status of healthcare waters between samples. Disinfection/decontamination is recommended to minimize bioburden and the effect of remediation should be verified with microbiological monitoring. Where standard remediation did not remove

P. aeruginosa

contamination, intensive monitoring supported justifying replacement of showers and contiguous plumbing.
A Roadmap to Artificial Intelligence (AI): Methods for Designing and Building AI ready Data for Women’s Health Studies
Authors: Kidwai-Khan Farah , Wang Rixin , Skanderson Melissa , Brandt Cynthia A. , Fodeh Samah , Womack Julie A.
Published: May 2023

Objectives

Evaluating methods for building data frameworks for application of AI in large scale datasets for women’s health studies.

Methods

We created methods for transforming raw data to a data framework for applying machine learning (ML) and natural language processing (NLP) techniques for predicting falls and fractures.

Results

Prediction of falls was higher in women compared to men. Information extracted from radiology reports was converted to a matrix for applying machine learning. For fractures, by applying specialized algorithms, we extracted snippets from dual x-ray absorptiometry (DXA) scans for meaningful terms usable for predicting fracture risk.

Discussion

Life cycle of data from raw to analytic form includes data governance, cleaning, management, and analysis. For applying AI, data must be prepared optimally to reduce algorithmic bias.

Conclusion

Algorithmic bias is harmful for research using AI methods. Building AI ready data frameworks that improve efficiency can be especially valuable for women’s health.

Lay Summary

Women’s health studies are rare in large cohorts of women. The department of Veterans affairs (VA) has data for a large number of women in care. Prediction of falls and fractures are important areas of study related to women’s health. Artificial Intelligence (AI) methods have been developed at the VA for predicting falls and fractures. In this paper we discuss data preparation for applying these AI methods. We discuss how data preparation can affect bias and reproducibility in AI outcomes.
TGIRT-seq of Inflammatory Breast Cancer Tumor and Blood Samples Reveals Widespread Enhanced Transcription Impacting RNA Splicing and Intronic RNAs in Plasma
Authors: Wylie Dennis , Wang Xiaoping , Yao Jun , Xu Hengyi , Ferrick-Kiddie Elizabeth A. , Iwase Toshiaki , Krishnamurthy Savitri , Ueno Naoto T. , Lambowitz Alan M.
Published: May 2023

Inflammatory breast cancer (IBC) is the most aggressive and lethal breast cancer subtype but lacks unequivocal genomic differences or robust biomarkers that differentiate it from non-IBC. Here, Thermostable Group II intron Reverse Transcriptase RNA-sequencing (TGIRT-seq) revealed myriad differences in tumor samples, Peripheral Blood Mononuclear Cells (PBMCs), and plasma that distinguished IBC from non-IBC patients and healthy donors across all tested receptor-based subtypes. These included numerous differentially expressed protein-coding gene and non-coding RNAs in all three sample types, a granulocytic immune response in IBC PBMCs, and over- expression of antisense RNAs, suggesting wide-spread enhanced transcription in both IBC tumors and PBMCs. By using TGIRT-seq to quantitate Intron-exon Depth Ratios (IDRs) and mapping reads to both genome and transcriptome reference sequences, we developed methods for parallel analysis of transcriptional and post-transcriptional gene regulation. This analysis identified numerous differentially and non-differentially expressed protein-coding genes in IBC tumors and PBMCs with high IDRs, the latter reflecting rate-limiting RNA splicing that negatively impacts mRNA production. Mirroring gene expression differences in tumors and PBMCs, over-represented protein-coding gene RNAs in IBC patient plasma were largely intronic RNAs, while those in non- IBC patients and healthy donor plasma were largely mRNA fragments. Potential IBC biomarkers in plasma included T-cell receptor pre-mRNAs and intronic, LINE-1, and antisense RNAs. Our findings provide new insights into IBC and set the stage for monitoring disease progression and response to treatment by liquid biopsy. The methods developed for parallel transcriptional and post- transcriptional gene regulation analysis have potentially broad RNA-seq and clinical applications.
Four classic “de novo” genes all have plausible homologs and likely evolved from retro-duplicated or pseudogenic sequences
Authors: Hannon Joseph
Published: May 2023

Despite being previously regarded as extremely unlikely, the idea that entirely novel protein-coding genes can emerge from non-coding sequences has gradually become accepted over the past two decades. Examples of “de novo origination”, resulting in lineage-specific “orphan” genes, lacking orthologs, are now produced every year. However, many are likely cases of duplicates that are difficult to recognize. Here, I re-examine the claims and show that four very well-known examples of genes alleged to have emerged de novo “from scratch” - namelyFLJ33706in humans,Goddardin fruit flies,BSC4in baker’s yeast andAFGP2in codfish - all have plausible evolutionary ancestors in pre-existing genes. In the case of the first two, highly diverged retrogenes that code for regulatory proteins may have been misidentified as being orphans. The antifreeze glycoproteins in cod, moreover, are shown to have likely not evolved from repetitive non-genic sequences but, as in other related cases, from an apolipoprotein that may well have been pseudogenized before later being reactivated. These findings detract from various claims made about de novo gene birth and show there has been a tendency not to invest the necessary effort in searching for homologs outside of a very limited syntenic or phylostratigraphic methodology. An approach used here for improving homology detection draws upon similarities, not just in terms of statistical sequence analysis, but also with biochemistry and function, in order to obviate failure.
Transformer with Convolution and Graph-Node co-embedding: An accurate and interpretable vision backbone for predicting gene expressions from local histopathological image
Authors: Xiao Xiao , Kong Yan , Wang Zuoheng , Lu Hui
Published: May 2023

Inferring gene expressions from histopathological images has always been a fascinating but challenging task due to the huge differences between the two modal data. Previous works have used modified DenseNet121 to encode the local images and make gene expression predictions. And later works improved the prediction accuracy of gene expression by incorporating the coordinate information from images and using all spots in the tissue region as input. While these methods were limited in use due to model complexity, large demand on GPU memory, and insufficient encoding of local images, thus the results had low interpretability, relatively low accuracy, and over-smooth prediction of gene expression among neighbor spots. In this paper, we propose TCGN, (Transformer with Convolution and Graph-Node co-embedding method) for gene expression prediction from H&E stained pathological slide images. TCGN consists of convolutional layers, transformer encoders, and graph neural networks, and is the first to integrate these blocks in a general and interpretable computer vision backbone for histopathological image analysis. We trained TCGN and compared its performance with three existing methods on a publicly available spatial transcriptomic dataset. Even in the absence of the coordinates information and neighbor spots, TCGN still outperformed the existing methods by 5% and achieved 10 times higher prediction accuracy than the counterpart model. Besides its higher accuracy, our model is also small enough to be run on a personal computer and does not need complex building graph preprocessing compared to the existing methods. Moreover, TCGN is interpretable in recognizing special cell morphology and cell-cell interactions compared to models using all spots as input that are not interpretable. A more accurate omics information prediction from pathological images not only links genotypes to phenotypes so that we can predict more biomarkers that are expensive to test from histopathological images that are low-cost to obtain, but also provides a theoretical basis for future modeling of multi-modal data. Our results support that TCGN is a useful tool for inferring gene expressions from histopathological images and other potential histopathological image analysis studies.

Highlights

First deep learning model to integrate CNN, GNN, and transformer for image analysis

An interpretable model that uses cell morphology and organizations to predict genes

Higher gene expression prediction accuracy without global information

Accurately predicted genes are related to immune escape and abnormal metabolism

Predict important biomarkers for breast cancer accurately from cheaper images

Graphical abstract
Epigenetics Insights from Perceived Facial Aging
Authors: Vladimir Klemo , Perišić Marija Majda , Štorga Mario , Mostashari Ali , Khanin Raya
Published: May 2023

Facial aging is the most visible manifestation of aging. People desire to look younger than others of the same chronological age. Hence, perceived age is often used as a visible marker of aging, while biological age, often estimated by methylation markers, is used as an objective measure of age. Multiple epigenetics-based clocks have been developed for accurate estimation of general biological age and the age of specific organs, including the skin. However, it is not clear whether the epigenetic biomarkers (CpGs) used in these clocks are drivers of aging processes or consequences of aging.

In this proof-of-concept study, we integrate data from GWAS on perceived facial aging, and EWAS on CpGs measured in blood. By running EW Mendelian randomization, we identify hundreds of putative CpGs that are potentially causal to perceived facial aging with similar numbers of damaging markers that causally drive or accelerate facial aging and protective methylation markers that causally slow down or protect from aging. We further demonstrate that while candidate causal CpGs have little overlap with known epigenetics-based clocks, they affect genes or proteins with known functions in skin aging such as skin pigmentation, elastin, and collagen levels. Overall, our results suggest that blood methylation markers reflect facial aging processes, and thus can be used to quantify skin aging and develop anti-aging solutions that target the root causes of aging.
Impaired neutrophil-mediated cell death drives Ewing’s Sarcoma in a two years old child with Down Syndrome
Authors: Peirone Serena , Tirtei Elisa , Campello Anna , Parlato Caterina , Guarrera Simonetta , Mareschi Katia , Marini Elena , Asaftei Sebastian Dorin , Bertero Luca , Papotti Mauro , Priante Francesca , Perrone Sarah , Cereda Matteo , Fagioli Franca
Published: May 2023

Ewing’s Sarcoma (EWS) has been reported in seven children with Down Syndrome (DS). To date, a detailed assessment of this solid tumor in DS patients is still missing. Here, we characterized a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches. The tumor showed a neuroectodermal development driven by the EWSR1-FLI1 fusion. The inherited myeloperoxidase deficiency of the patient caused failure of neutrophil-mediated cell death and promoted genomic instability. In this context, the tumor underwent nearly genome-wide haploidization resulting in a massive overexpression of pro-inflammatory cytokines. Recruitment of defective neutrophils fostered the fast evolution of this EWS.
HMGB1 acts as an agent of host defense at the gut mucosal barrier
Authors: Overstreet A-M C , Anderson B , Burge M , Zhu X , Tao Y , Cham CM , Michaud B , Horam S , Sangwan N , Dwidar M , Liu X , Santos A , Finney C , Dai Z , Leone VA , Messer JS
Published: May 2023

Mucosal barriers provide the first line of defense between internal body surfaces and microbial threats from the outside world.1In the colon, the barrier consists of two layers of mucus and a single layer of tightly interconnected epithelial cells supported by connective tissue and immune cells.2Microbes colonize the loose, outer layer of colonic mucus, but are essentially excluded from the tight, epithelial-associated layer by host defenses.3The amount and composition of the mucus is calibrated based on microbial signals and loss of even a single component of this mixture can destabilize microbial biogeography and increase the risk of disease.4–7However, the specific components of mucus, their molecular microbial targets, and how they work to contain the gut microbiota are still largely unknown. Here we show that high mobility group box 1 (HMGB1), the prototypical damage-associated molecular pattern molecule (DAMP), acts as an agent of host mucosal defense in the colon. HMGB1 in colonic mucus targets an evolutionarily conserved amino acid sequence found in bacterial adhesins, including the well-characterized Enterobacteriaceae adhesin FimH. HMGB1 aggregates bacteria and blocks adhesin-carbohydrate interactions, inhibiting invasion through colonic mucus and adhesion to host cells. Exposure to HMGB1 also suppresses bacterial expression of FimH. In ulcerative colitis, HMGB1 mucosal defense is compromised, leading to tissue-adherent bacteria expressing FimH. Our results demonstrate a new, physiologic role for extracellular HMGB1 that refines its functions as a DAMP to include direct, virulence limiting effects on bacteria. The amino acid sequence targeted by HMGB1 appears to be broadly utilized by bacterial adhesins, critical for virulence, and differentially expressed by bacteria in commensal versus pathogenic states. These characteristics suggest that this amino acid sequence is a novel microbial virulence determinant and could be used to develop new approaches to diagnosis and treatment of bacterial disease that precisely identify and target virulent microbes.
Lymphoid tissues contribute to viral clonotypes present in plasma at early post-ATI in SIV-infected rhesus macaques
Authors: Solis-Leal Antonio , Boby Nongthombam , Mallick Suvadip , Cheng Yilun , Wu Fei , De La Torre Grey , Dufour Jason , Alvarez Xavier , Shivanna Vinay , Liu Yaozhong , Fennessey Christine M. , Lifson Jeffrey D. , Li Qingsheng , Keele Brandon F. , Ling Binhua
Published: May 2023

The rebound-competent viral reservoir (RCVR), comprised of virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after antiretroviral therapy interruption (ATI), remains the biggest obstacle to the eradication of HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop targeted therapeutic strategies for reducing the RCVR. In this study, barcoded SIVmac239M was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood, lymphoid tissues (LTs, spleen, mesenteric and inguinal lymph nodes), and non-lymphoid tissues (NLTs, colon, ileum, lung, liver, and brain) were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX/RNAscope/in situhybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy although plasma viral RNA remained < 22 copies/mL. Among the tissues studied, mesenteric and inguinal lymph nodes, and spleen contained viral barcodes detected in plasma, and trended to have higher cell-associated viral loads, higher intact provirus levels, and greater diversity of viral barcodes. CD4+ T cells were the main cell type harboring viral RNA (vRNA) after ATI. Further, T cell zones in LTs showed higher vRNA levels than B cell zones for most animals. These findings are consistent with LTs contributing to virus present in plasma early after ATI.

One Sentence Summary

The reemerging of SIV clonotypes at early post-ATI are likely from the secondary lymphoid tissues.
Characterisation of thein-vivomiRNA landscape inDrosophilaribonuclease mutants reveals Pacman mediated regulation of the highly conservedlet-7cluster during apoptotic processes
Authors: Bernard Elisa I. M. , Towler Benjamin P. , Newbury Sarah F.
Published: May 2023

The control of gene expression is a fundamental process essential for correct development and to maintain homeostasis. Many post-transcriptional mechanisms exist to maintain the correct levels of each RNA transcript within the cell. Controlled and targeted cytoplasmic RNA degradation is one such mechanism with the 5’-3’ exoribonuclease Pacman (XRN1) and the 3’-5’ exoribonuclease Dis3L2 playing crucial roles. Loss of function mutations in either Pacman or Dis3L2 have been demonstrated to result in distinct phenotypes, and both have been implicated in human disease. One mechanism by which gene expression is controlled is through the function of miRNAs which have been shown to be crucial for the control of almost all cellular processes. Although the biogenesis and mechanisms of action of miRNAs have been comprehensively studied, the mechanisms regulating their own turnover are not well understood. Here we characterise the miRNA landscape in a natural developing tissue, theDrosophila melanogasterwing imaginal disc, and assess the importance of Pacman and Dis3L2 on the abundance of miRNAs. We reveal a complex landscape of miRNA expression and show that whilst a null mutation indis3L2has a minimal effect on the miRNA expression profile, loss of Pacman has a profound effect with a third of all detected miRNAs demonstrating Pacman-sensitivity. We also reveal a role of Pacman in regulating the highly conservedlet-7cluster (containingmiR-100, let-7andmiR-125) and present a genetic model outlining a positive feedback loop regulated by Pacman which begins to explain the apoptotic phenotype observed in Pacman mutants.
Rank-based deep learning from citizen-science data to model plant communities
Authors: Brun Philipp , Karger Dirk N. , Zurell Damaris , Descombes Patrice , de Witte Lucienne C. , de Lutio Riccardo , Wegner Jan Dirk , Zimmermann Niklaus E.
Published: May 2023

In the age of big data, scientific progress is fundamentally limited by our capacity to extract critical information. We show that recasting multispecies distribution modeling as a ranking problem allows analyzing ubiquitous citizen-science observations with unprecedented efficiency. Based on 6.7M observations, we jointly modeled the distributions of 2477 plant species and species aggregates across Switzerland, using deep neural networks (DNNs). Compared to commonly-used approaches, multispecies DNNs predicted species distributions and especially community composition more accurately. Moreover, their setup allowed investigating understudied aspects of ecology: including seasonal variations of observation probability explicitly allowed approximating flowering phenology, especially for small, herbaceous species; reweighting predictions to mirror cover-abundance allowed mapping potentially canopy-dominant tree species nationwide; and projecting DNNs into the future allowed assessing how distributions, phenology, and dominance may change. Given their skill and their versatility, multispecies DNNs can refine our understanding of the distribution of plants and well-sampled taxa in general.
Denaturing mass photometry for straightforward optimization of protein-protein cross-linking reactions at single-molecule level
Authors: Gizardin-Fredon Hugo , Santo Paulo E. , Chagot Marie-Eve , Charpentier Bruno , Bandeiras Tiago M. , Manival Xavier , Hernandez-Alba Oscar , Cianférani Sarah
Published: May 2023

Mass photometry (MP) is a versatile, fast and low sample-consuming biophysical technique that gained interest in structural biology to study noncovalent assemblies in native conditions. We report here on a novel method to perform MP analysis in denaturing conditions (dMP) and its application for fast, accurate and straightforward optimization of chemical reactions in cross-linking mass spectrometry (XL-MS) workflows. dMP consists in a robust 2-step protocol that ensures 95% of irreversible denaturation within only 5 min. The proposed single-molecule method clearly overcomes the limitations and outperforms gold standard SDS-PAGE, as illustrated on several biological complexes. dMP provides an unprecedented and unmatched in-solution quantification of all coexisting XL species, including sub-complexes and non-specific XL aggregates, along with identification of significantly higher numbers of XL dipeptides in MS. We anticipate single-molecule dMP to be a high-impact game-changer for the XL-MS community with the potential to leverage the quality and reliability of XL-MS datasets.
EWS::FLI1-DHX9 interaction promotes Ewing sarcoma sensitivity to DNA topoisomerase 1 poisons by altering R-loop metabolism
Authors: Olmedo-Pelayo Joaquin , Granado-Calle Esperanza , Delgado-Bellido Daniel , Lobo-Selma Laura , Jordán-Pérez Carmen , Monteiro-Amaral Ana T. , Ehlers Anna C. , Ohmura Shunya , Carcaboso Angel M. , Alonso Javier , Machado Isidro , Llombart-Bosch Antonio , Grünewald Thomas G.P. , Gómez-Herreros Fernando , de Álava Enrique
Published: May 2023

Drug resistance is one of the major factors associated with poor outcome of cancer patients. Treatment of Ewing sarcoma (EwS), an aggressive neoplasm mainly affecting children, adolescents and young adults, is associated with therapy failure and tumor relapse in 30-80% of the cases. Thus, it supports the need to explore the mechanisms modulating drug activity. Here, we describe a novel mechanism of drug sensitivity based on the role of EWS::FLI1 in R-loop metabolism. Our results demonstrate that EWS::FLI1 promotes R-loop formation favoring the interaction between DHX9 and elongating RNA polymerase II. In addition, we discovered that EWS::FLI1 kidnaps DHX9 preventing the resolution of TOP1 poisoning-associated R-loops. Our findings indicate that R-loops accumulation promotes replicative stress, genome instability and cell sensitivity to SN-38. Collectively, these results uncover a novel mechanism behind EwS sensitivity to genotoxic agents, with relevant implications for EwS treatment.
A new vulnerability to BET inhibition due to enhanced autophagy in BRCA2 deficient pancreatic cancer
Authors: Lee EunJung , Archasappawat Suyakarn , Ji Keely , Pena Jocelyn , Fernandez-Vega Virneliz , Gangaraju Ritika , Beesabathuni Nitin Sai , Kim Martin Jean , Tian Qi , Shah Priya , Scampavia Louis , Spicer Timothy , Hwang Chang-Il
Published: May 2023

Pancreatic cancer is one of the deadliest diseases in human malignancies. Among total pancreatic cancer patients, ∼10% of patients are categorized as familial pancreatic cancer (FPC) patients, carrying germline mutations of the genes involved in DNA repair pathways (e.g., BRCA2). Personalized medicine approaches tailored toward patients’ mutations would improve patients’ outcome. To identify novel vulnerabilities ofBRCA2-deficient pancreatic cancer, we generated isogenicBrca2-deficient murine pancreatic cancer cell lines and performed high-throughput drug screens. High-throughput drug screening revealed thatBrca2-deficient cells are sensitive to Bromodomain and Extraterminal Motif (BET) inhibitors, suggesting that BET inhibition might be a potential therapeutic approach. We found thatBRCA2deficiency increased autophagic flux, which was further enhanced by BET inhibition inBrca2-deficient pancreatic cancer cells, resulting in autophagy-dependent cell death. Our data suggests that BET inhibition can be a novel therapeutic strategy forBRCA2-deficient pancreatic cancer.
Chlamydial YAP activation in host endocervical epithelial cells mediates pro-fibrotic paracrine stimulation of fibroblasts
Authors: Caven Liam , Carabeo Rey
Published: May 2023

Infection of the female genital tract byChlamydia trachomatiscan produce severe fibrotic sequelae, including tubal factor infertility and ectopic pregnancy. While infection demonstrably mediates a pro-fibrotic response in host cells, it remains unclear if intrinsic properties of the upper genital tract exacerbate chlamydial fibrosis. The relatively sterile environment of the upper genital tract is primed for a pro-inflammatory response to infection, potentially enhancing fibrosis - however, subclinicalC. trachomatisinfections still develop fibrosis-related sequelae. Here, we compare infection-associated and steady-state gene expression of primary human cervical and vaginal epithelial cells. In the former, we observe enhanced baseline expression and infection-mediated induction of fibrosis-associated signal factors (e.g.TGFA,IL6,IL8,IL20), implying predisposition toChlamydia-associated pro-fibrotic signaling. Transcription factor enrichment analysis identified regulatory targets of YAP, a transcriptional cofactor induced by infection of cervical epithelial cells, but not vaginal epithelial cells. YAP target genes induced by infection include secreted fibroblast-activating signal factors; therefore, we developed anin vitromodel involving coculture of infected endocervical epithelial cells with uninfected fibroblasts. Coculture enhanced fibroblast expression of type I collagen, as well as prompting reproducible (albeit statistically insignificant) induction of α-smooth muscle actin. Fibroblast collagen induction was sensitive to siRNA-mediated YAP knockdown in infected epithelial cells, implicating chlamydial YAP activation in this effect. Collectively, our results present a novel mechanism of fibrosis initiated byChlamydia,wherein infection-mediated induction of host YAP facilitates pro-fibrotic intercellular communication. Chlamydial YAP activation in cervical epithelial cells is thus a determinant of this tissue’s susceptibility to fibrosis.

Importance

Chronic or repeated infection of the female upper genital tract byC. trachomatiscan lead to severe fibrotic sequelae, including tubal factor infertility and ectopic pregnancy. However, the molecular mechanisms underlying this effect are unclear. In this report, we define a transcriptional program specific toC. trachomatisinfection of the upper genital tract, identifying tissue-specific induction of host YAP – a pro-fibrotic transcriptional cofactor – as a potential driver of infection-mediated fibrotic gene expression. Further, we show that infected endocervical epithelial cells stimulate collagen production by fibroblasts, and implicate chlamydial induction of YAP in this effect. Our results define a mechanism by which infection mediates tissue-level fibrotic pathology via paracrine signaling, and identify YAP as a potential therapeutic target for prevention ofChlamydia-associated scarring of the female genital tract.
Structural basis of regioselective tryptophan dibromination by the single-component flavin-dependent halogenase AetF
Authors: Gäfe Simon , Niemann Hartmut H.
Published: May 2023

The flavin-dependent halogenase (FDH) AetF successively brominates tryptophan at C5 and C7 to generate 5,7-dibromotryptophan. In contrast to the well studied two-component tryptophan halogenases, AetF is a single-component flavoprotein monooxygenase. Here, crystal structures of AetF alone and in complex with various substrates are presented, representing the first experimental structures of a single-component FDH. Rotational pseudosymmetry and pseudomerohedral twinning complicated the phasing of one structure. AetF is structurally related to flavin-dependent monooxygenases. It contains two dinucleotide-binding domains for binding the ADP moiety with unusual sequences that deviate from the consensus sequences GXGXXG and GXGXXA. A large domain tightly binds the cofactor flavin adenine dinucleotide (FAD), while the small domain responsible for binding the nicotinamide adenine dinucleotide (NADP) is unoccupied. About half of the protein forms additional structural elements containing the tryptophan binding site. FAD and tryptophan are about 16 Å apart. A tunnel between them presumably allows diffusion of the active halogenating agent hypohalous acid from FAD to the substrate. Tryptophan and 5-bromotryptophan bind to the same site but with a different binding pose. A flip of the indole moiety identically positions C5 of tryptophan and C7 of 5-bromotryptophan next to the tunnel and to catalytic residues, providing a simple explanation for the regioselectivity of the two successive halogenations. AetF can also bind 7-bromotryptophan in the same orientation as tryptophan. This opens the way for the biocatalytic production of differentially dihalogenated tryptophan derivatives. The structural conservation of a catalytic lysine suggests a way to identify novel single-component FDHs.
Metaverse in marketing and logistics: the state of the art and the path forward
Authors: Tan Garry Wei-Han , Aw Eugene Cheng-Xi , Cham Tat-Huei , Ooi Keng-Boon , Dwivedi Yogesh K. , Alalwan Ali Abdallah , Balakrishnan Janarthanan , Chan Hing Kai , Hew Jun-Jie , Hughes Laurie , Jain Varsha , Lee Voon Hsien , Lin Binshan , Rana Nripendra P. , Tan Teck Ming
Published: May 2023

Purpose

Ever since its emergence, the metaverse has presented opportunities and disruptions to every stakeholder, including individual users and organizations. This article aims to offer valuable perspectives on six identified critical areas that the metaverse could significantly impact: marketing ethics, marketing communication, relationship marketing, retail marketing, supply chain management and transportation management.

Design/methodology/approach

Through a multi-perspective approach, this paper gathers valuable perspectives from various invited contributors to each of the six identified key areas that the metaverse could significantly impact.

Findings

For each key area identified, the invited contributors first share their valuable perspectives by discussing the roles of the metaverse. Subsequently, the invited contributors discuss their views on vital opportunities, challenges and research agenda concerning the metaverse.

Originality/value

With the widespread metaverse, it is expected that each key area identified is likely to undergo significant levels of disruption. Against this backdrop, this paper contributes to the academic literature and industry by gathering different perspectives from invited contributors on the relevance of the metaverse in marketing and logistics domains.
Circular information flows in industrialized housing construction: the case of a multi-family housing product platform in Sweden
Authors: Kedir Firehiwot , Hall Daniel M. , Brantvall Sara , Lessing Jerker , Hollberg Alexander , Soman Ranjith K.
Published: May 2023

Purpose

This paper aims to conduct a qualitative assessment of synergies between information flows of a multifamily product platform used for industrialized housing and materials passports that can promote a circular economy in the construction industry.

Design/methodology/approach

Using a single case study method, the research assesses the availability and accessibility of materials passport-relevant information generated by a leading Swedish industrialized housing construction firm. Data is collected using semistructured interviews, document analysis and an extended research visit.

Findings

The research findings identify the functional layers of the product platform, map the information flow using a process diagram, assess the availability and accessibility of material passport relevant information by lifecycle stage and actor, and summarize the key points using a SWOT (strengths, weaknesses, opportunities and threats) analysis.

Research limitations/implications

The three main implications are: the technical and process platforms used in industrialized construction allow for generating standardized, digital and reusable information; the vertical integration of trades and long-term relationships with suppliers improve transparency and reduce fragmentation in information flows; and the design-build-operate business model strategy incentivizes actors to manage information flows in the use phase.

Practical implications

Industrialized construction firms can use this paper as an approach to understand and map their information flows to identify suitable approaches to generate and manage materials passports.

Originality/value

The specific characteristics of product platforms and industrialized construction provide a unique opportunity for circular information flow across the building lifecycle, which can support material passport adoption to a degree not often found in the traditional construction industry.
Stiffness of three-bar tensegrity structure
Authors: Luo Ani , Cao Ziying , Liu Heping , Feng Yaming
Published: May 2023

Purpose

In this paper, the main factors influencing the structure stiffness will be analyzed by studying the tangent stiffness matrix based on different requirement in engineering practice. The authors can obtain the deformation of three-bar tensegrity basic unit in different load, and gain the primary factor by comparing the deformation, which will provide reference to concrete structure design in the engineering.

Design/methodology/approach

The mathematical model of tensegrity structure was built by establishing generalized node coordinates and connective matrix. Three main factors that affect the structure deformation can be obtained by analyzing the stiffness matrix, which is preload, Young's modulus, and cross-sectional area, the thinking of deformation also be sorted out. The deformation analysis of the concrete structure is carried out, and it is concluded that increasing the cross-sectional area can quickly improve the stiffness of the structure, which provides a reference for the structural variable stiffness design in practical engineering.

Findings

(1) When the axial external force is applied to the structure, the torsion-angle deformation of the structure is the largest, and the radial deformation of the structure is the smallest. (2) The structure stiffness can be rapidly enhanced by increasing the cross-sectional area. But the cross-sectional area can't be increased indefinitely. Because the mass will be increased once increasing the cross-sectional area, which will destroy the structure of the advantages of light weight in engineering practice.

Originality/value

The deformation analysis of the concrete structure is carried out, and it is concluded that increasing the cross-sectional area can quickly improve the stiffness of the structure, which provides a reference for the structural variable stiffness design in practical engineering.
Impact of teaching-learning approaches on graduates' learning outcomes: evidence in Belarus
Authors: Isusi-Fagoaga Rosa , García-Aracil Adela , Navarro-Milla Isidora
Published: May 2023

Purpose

This paper analyses teachers' perceptions of how teaching-learning approaches affect the development of higher education (HE) graduates' learning outcomes based on competencies development. The authors focus the analysis on Belarus, a post-Soviet country which transitioned from a centrally planned to a market economy and needs reforms to the HE sector there. In particular, Belarus requires HE graduates equipped with competencies that match the needs of a market economy.

Design/methodology/approach

The authors use Fostering Competencies Development in Belarusian Higher Education (FOSTERC) data to study how teachers contribute to the development of HE graduates' competencies, employing factor analysis to categorize 24 competencies and group the graduates into two groups: entrepreneurial or transversal. The authors also consider variables such as teachers' educational background and experience, predominant teaching field of study and university location – using regional dummies.

Findings

The results point to a lack of attention to entrepreneurial and transversal competencies and suggest a disconnect between HE and society needs in Belarus.

Originality/value

Although Belarus has introduced some changes to the HE system following the adoption of the Bologna process, Belarus, especially Belarus' national HE system are still influenced by the country's Soviet past, where universities prepare the students for participation on one job and one career, instead of offering more attractive and constructive curricula that would allow future graduates to operate in a changing world.
Why targeting attitudes often fails to elicit sustainable tourist behaviour
Authors: Dolnicar Sara , Demeter Csilla
Published: May 2023

Purpose

Recent reviews of field experiments aiming to entice tourists to behave in more environmentally sustainable ways conclude that attitudes – while the primary target – do not perform as well as expected. The purpose of this study is to analyse in detail when attitudes have or have not been successful as behavioural change targets and propose a conceptual framework of possible explanations. In so doing, this study represents the first theoretical – rather than empirical – challenge to the currently dominant theoretical understanding of environmentally significant tourist behaviours and offers alternative theoretical constructs tourism researchers aiming to make tourists behave in more sustainable ways could investigate in future.

Design/methodology/approach

The authors investigate in detail experiments where attitude-based behavioural change approaches failed. Based on the insights from this analysis, the authors propose a conceptual framework offering five potential explanations. This study also discusses alternative theoretical constructs that could be used for behavioural change interventions.

Findings

The authors derive five potential explanations for why attitudes often fail to trigger behavioural change in the context of environmentally sustainable tourist behaviour: tourists do not notice messages attempting to change their attitudes; tourists are unwilling to cognitively process behavioural change messages; tourists develop reactance to behavioural change requests; attempts to alter attitudes do not influence habits; and attempts to alter attitudes do not reduce the effort associated with displaying the desired behaviour.

Research limitations/implications

This study broadens research attention to alternative theoretical constructs that may be more effective in making tourists behave in more sustainable ways and opens opportunities for new measures tourism businesses and destinations can implement to influence tourist behaviour.

Originality/value

To the best of the authors’ knowledge, this is the first theoretical investigation of possible reasons why attitudes have performed poorly as targets of behavioural change interventions aiming to trigger environmentally sustainable tourist behaviours.
Family travel among people with autism: challenges and support needs
Authors: Zhao Zhiyue , Shi Da , Qi Xiaoxiao , Shan Yawen , Liu Xiyi
Published: May 2023

Purpose

People with autism and their families struggle with travel because of its complexity. This study aims to promote travel participation by exploring the travel needs and patterns of people with autism and their families.

Design/methodology/approach

A total of 28 participants were interviewed. Data were analyzed via constructivist grounded theory.

Findings

People with autism and their families displayed five travel patterns: mutual support, relatives’ visitation, independent travel, expanded socialization and package tours. These patterns were adopted in a stepwise fashion as the autistic individuals’ abilities improved. The travel challenges and support needs of Chinese autistic people and their families were identified.

Practical implications

The findings can inform accessibility tourism, promote an understanding of autistic people’s tourism activities among the public and industry marketers and offer strategic guidance about family travel for this population.

Originality/value

This effort responds to a call to investigate disability-related issues. The study evaluated the travel behavior of people with autism and their families, from a developmental perspective, presenting a new angle in research on accessibility tourism.
The influence of performance-driven cultures on performance appraisal best practices effectiveness
Authors: Botelho Carlos
Published: May 2023

Purpose

This paper aims to analyze the synergistic influence of performance appraisal (PA) practices and performance-driven culture (PDC) on the effectiveness of the performance management (PM) system, which is measured by employees' reactions, namely satisfaction and perceived utility. It also analyzes the type of relationship between PA practices and PA satisfaction, specifically whether it is additive or modeled as a latent factor.

Design/methodology/approach

This is a cross-sectional study. Data were collected from 513 managers and employees working in 135 public and private organizations. The research model and hypotheses were tested using structured equation modeling.

Findings

The results support the positive impact of a set of four PA best practices on PA satisfaction. It shows that PDC is an enabler for the effective deployment of PA practices. It also demonstrates that the perceived utility of the PM system plays a role as a mediator in the relationship between PA practices and PA satisfaction.

Research limitations/implications

Data were collected using a questionnaire at a single point in time, and thus, cause-and-effect inferences were not possible.

Practical implications

The results provide guidance to organizations that are interested in designing and implementing PM systems and PA practices that contribute toward enhancing employees' managing performance experiences.

Originality/value

This study advances our understanding of the mechanisms by which organizational culture and PA practices influence the effectiveness of the PM system. It suggests that organizations, to benefit the most from a set of PA best practices, need to have a PDC.
Designing an information-sharing system to improve collaboration culture: a soft systems methodology approach in the digital service creation process
Authors: Devi Ervia Tissyaraksita , Wibisono Dermawan , Mulyono Nur Budi , Fitriati Rachma
Published: May 2023

Purpose

This study aims to fill the gap in collaboration culture improvement by designing an information-sharing system as an enabler to support the forming dimensions of the collaboration process in previous studies. The authors propose the appropriate system to eliminate the collaboration culture gaps between the related functional units based on in-process interaction learning in a business process outsourcing company.

Design/methodology/approach

This study employed action research (AR) based on soft systems methodology (SSM) with a system thinking approach, in which the authors and process actors design the agreed information-sharing system by involving the process actors in identifying the initial problem situation as well as validating the conceptual model through discussions and designing the expected system.

Findings

This study discovers that SSM-based AR is a suited method for designing a system that supports the formation of collaboration culture among actors in the digital service creation process by learning user perceptions and expectations in order to obtain their commitment to empower the proposed system.

Originality/value

In addition to providing a system to minimize the lack of collaboration culture, this study contributes to the academic literature by offering a new way of planning and designing in a system development methodology using soft systems approaches to understand user perceptions, expressing user interaction in a conceptual model and validating it and defining agreed activities to obtain the best design according to user expectations.