bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SummaryEwing’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

AbstractMucosal 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

AbstractThe 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 SummaryThe 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

ABSTRACTThe 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

AbstractIn 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

ABSTRACTMass 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

AbstractDrug 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

AbstractPancreatic 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

AbstractInfection 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.ImportanceChronic 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.
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

PurposeEver 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/approachThrough 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.FindingsFor 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/valueWith 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

PurposeIn 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/approachThe 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/valueThe 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

PurposeThis 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/approachThe 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.FindingsThe results point to a lack of attention to entrepreneurial and transversal competencies and suggest a disconnect between HE and society needs in Belarus.Originality/valueAlthough 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.