bluuebunny/crossref_metadata_2025 huggingface dataset:
ANKRD49 promotes the metastasis of NCI-H1299 and NCI-H1703 cells via activating JNK-ATF2/c-Jun-MMP-2/9 axis
Authors: Sun Jia , Hu Jin-rui , Liu Chao-feng , Li Yuan , Wang Wei , Fu Rong , Guo Min , Wang Hai-long , Pang Min
Published: March 2023

Ankyrin repeat domain 49 (ANKRD49) has been found to highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify. We found that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9.In vivoassay showed that ANKRD49 promoted lung metastasis of injected- NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2. In conclusion, the present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9.
Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons
Authors: Saito-Diaz Kenyi , Dietrich Paula , Wu Hsueh-Fu , Sun Xin , Jayesh Patel Archie , Gale Wzientek Camryn , Robert Prudden Anthony , Boons Geert-Jan , Chen Shuibing , Studer Lorenz , Xu Bingqian , Dragatsis Ioannis , Zeltner Nadja
Published: March 2023

The peripheral nervous system (PNS) is essential for proper body function. A high percentage of the population suffer nerve degeneration or peripheral damage. For example, over 40% of patients with diabetes or undergoing chemotherapy develop peripheral neuropathies. Despite this, there are major gaps in the knowledge of human PNS development and therefore, there are no available treatments. Familial Dysautonomia (FD) is a devastating disorder that specifically affects the PNS making it an ideal model to study PNS dysfunction. FD is caused by a homozygous point mutation inELP1leading to developmental and degenerative defects in the sensory and autonomic lineages. We previously employed human pluripotent stem cells (hPSCs) to show that peripheral sensory neurons (SNs) are not generated efficiently and degenerate over time in FD. Here, we conducted a chemical screen to identify compounds able to rescue this SN differentiation inefficiency. We identified that genipin, a compound prescribed in Traditional Chinese Medicine for neurodegenerative disorders, restores neural crest and SN development in FD, both in the hPSC model and in a FD mouse model. Additionally, genipin prevented FD neuronal degeneration, suggesting that it could be offered to patients suffering from PNS neurodegenerative disorders. We found that genipin crosslinks the extracellular matrix, increases the stiffness of the ECM, reorganizes the actin cytoskeleton, and promotes transcription of YAP-dependent genes. Finally, we show that genipin enhances axon regeneration in anin vitroaxotomy model in healthy sensory and sympathetic neurons (part of the PNS) and in prefrontal cortical neurons (part of the central nervous system, CNS). Our results suggest genipin can be used as a promising drug candidate for treatment of neurodevelopmental and neurodegenerative diseases, and as a enhancer of neuronal regeneration.

One sentence summary

Genipin rescues the developmental and degenerative phenotypes of the peripheral neuropathy familial dysautonomia and enhances neuron regeneration after injury.
Expanding Interdisciplinarity: A bibliometric study of medical education using the MEJ-24
Authors: Maggio Lauren A. , Costello Joseph A. , Ninkov Anton B. , Frank Jason R. , Artino Anthony R.
Published: March 2023

Introduction

Interdisciplinary research has been deemed to be critical in solving society’s wicked problems, including those relevant to medical education. Medical education research has been assumed to be interdisciplinary. However, researchers have questioned this assumption. The present study, a conceptual replication, provides an analysis using a larger dataset and bibliometric methods to bring more clarity to our understanding on the nature of medical education interdisciplinarity or lack thereof.

Method

The authors retrieved the cited references of all published articles in 24 medical education journals between 2001-2020 from the Web of Science (WoS). We then identified the WoS classifications for the journals of each cited reference.

Results

The 24 journals published 31,283 articles referencing 723,683 publications. We identified 493,973 (68.3%) of those cited references in 6,618 journals representing 242 categories, which represents 94% of all WoS categories. Close to half of all citations were categorized as “education, scientific disciplines” and “healthcare sciences and services”. Over the two decades studied, we observed consistent growth in the number of references in other categories, such as education, educational research, and nursing. Additionally, the variety of categories represented has also increased from 182 to 233 to include a diversity of topics such as business, management, and linguistics.

Discussion

This study corroborates prior work while also expanding it. Medical education research is built upon a limited range of fields referenced. Yet, the growth in categories over time and the ongoing increased diversity of included categories suggests interdisciplinarity that until now has yet to be recognized and represents a changing story.
Integrating EM and Patch-seq data: Synaptic connectivity and target specificity of predicted Sst transcriptomic types
Authors: Gamlin C.R. , Schneider-Mizell C.M. , Mallory M. , Elabbady L. , Gouwens N. , Williams G. , Mukora A. , Dalley R. , Bodor A. , Brittain D. , Buchanan J. , Bumbarger D. , Kapner D. , Kinn S. , Mahalingam G. , Seshamani S. , Takeno M. , Torres R. , Yin W. , Nicovich P.R. , Bae J.A. , Castro M.A. , Dorkenwald S. , Halageri A. , Jia Z. , Jordan C. , Kemnitz N. , Lee K. , Li K. , Lu R. , Macrina T. , Mitchell E. , Mondal S.S. , Mu S. , Nehoran B. , Popovych S. , Silversmith W. , Turner N.L. , Wong W. , Wu J. , Yu S. , Berg J. , Jarsky T. , Lee B. , Seung H.S. , Zeng H. , Reid R.C. , Collman F. , da Costa N.M. , Sorensen S. A.
Published: March 2023

Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types1. Neural cell types have previously been defined by morphology2, 3, electrophysiology4, 5, transcriptomic expression6–8, connectivity9–13, or even a combination of such modalities14–16. More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells17–20. Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex21. It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type22, 23known to be Somatostatin positive (Sst+)24, 25, were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types.
Knockdown of Atg1 or Atg18 in adult adipocytes impairs lipophagy and reduces lifespan of fruit flies (Drosophila melanogaster)
Authors: Bierlein Mariah , Charles Joseph , Polisuk-Balfour Trevor , Bretscher Heidi , Rice Micaela , Zvonar Jacklyn , Pohl Drake , Winslow Lindsey , Wasie Brennah , Deurloo Sara , Wert Jordan Van , Williams Britney , Ankney Gabrielle , Harmon Zachary , Dann Erica , Azuz Anna , Guzman-Vargas Alex , Kuhns Elizabeth , Neufeld Thomas P. , O’Connor Michael B. , Amissah Felix , Zhu Changqi C.
Published: March 2023

Autophagy, a lysosome-based eukaryotic cellular degradation system, has previously been implicated in lifespan regulation in different animal models. In this report, we show that expression of the RNAi transgenes targeting the transcripts of the key autophagy genes such asAtg1orAtg18in adult fly muscle or glia does not affect the overall levels of autophagosomes in those tissues and does not change the lifespan of the tested flies, but lifespan reduction phenotype has become apparent whenAtg1RNAi orAtg18RNAi is expressed in a non-tissue-specific manner through aTub-Gal4in adult flies or after lipophagy is eradicated through the knockdown of Atg1 or Atg18 in adult fly adipocytes. Lifespan reduction was also observed when Atg1 or Atg18 was knocked down in adult fly enteroblasts and middle gut stem cells. Over-expression of wildtype Atg1 in adult fly muscle or adipocytes reduces lifespan. High levels of ubiquitinated protein aggregates could be the culprit of the reduced lifespan of Atg1 over-expression flies. Our research data presented here have highlighted the important functions of the key autophagy genes in adult fly adipocytes, enteroblasts, and midgut stem cells for lifespan regulation and their undetermined functions in adult fly muscle and glia.

In this research, we have demonstrated that the key autophagy genes play important roles in fly lifespan regulation through adult adipose tissues, enteroblasts, and middle gut stem cells.
Mutafy: A webserver to identify high quality mutant protein structures in the Protein Data Bank
Authors: Ness Deborah , Hu Jiajing , Kalia Munishikha , Dobson Richard JB , Al-Chalabi Ammar , Iacoangeli Alfredo
Published: March 2023

Changes in the amino acid sequence of proteins resulting from nonsynonymous variants in the genome, can have significant effects on protein folding, stability, dynamics, and function, which may ultimately lead to diseases. The analysis of large sets of disease associated variants is a common approach for the study of pathogenic mechanisms.In-silicomutagenesis experiments based on wildtype structures of target proteins are a common approach to this aim, however these do not account for the effect of variants on folding and might not accurately reflect conformational changes. A growing number of experimentally solved protein structures harbouring disease-associated mutations, including single amino acid variants, are deposited in the worldwide Protein Data Bank (PDB). Nevertheless, identifying high-quality structures for specific missense variants of interest remains challenging due to the growing number of deposited protein structures in the PDB, and the lack of a dedicated interface and annotation system to search and retrieve mutant protein structures. As a result, mutant protein structures in the PDB are a powerful source of information which is largely underused. To address these shortcomings, we have developed Mutafy, a publicly available webserver to identify high quality mutant protein structures. Given input human genes, the webserver finds structures of the corresponding coded wildtype proteins and their available solved mutants, selects high quality structures, annotates them with information from biomedical databases to favour their interpretation and selection, and allows for the interactive exploration of the results and 3D visualisation. Mutafy is publicly available without requiring user registration athttps://mutafy.rosalind.kcl.ac.uk.
Isolation and whole genome characterization of antagonisticPaenibacillus polymyxa188 and its biocontrol potential against several fungi
Authors: Shih Sra-Yh , Chou Ker-Rui , Wu Hung-Yi , Tsai HsinYuan
Published: March 2023

Discovery of new antifungal compounds and biocontrol agents is important due to the emergence of drug-resistant fungi and new fungal pathogens. The aim of this study was to isolate marine bacteria that are able to produce metabolites with antifungal properties. In this study, we isolated aP. polymyxa,named as 188, from a marine sediment sample and evaluated its antifungal ability. The results indicated that the bacterium showed excellent antifungal activity against many pathogenic fungi of plants and humans. The antifungal compounds produced byP. polymyxa188 were extracted and analyzed using MALDI-TOF/MS. The complete genome sequence and biosynthetic gene clusters were characterized, and further to compare the genomes ofP. polymyxa188 with other strains. Various CAZymes were identified inP. polymyxa188. Five antibiotic gene clusters including paenilan, paenibacillin, fusaricidin, polymyxin, and tridecaptin can be found inP. polymyxastrains, but gene clusters of paenilan, paenibacillin, and polymyxin were absent inP. polymyxa188. Our findings provided detail genetic information aboutP. polymyxa188 and suggested thatP. polymyxa188 is the potential agent of biocontrol and disease management.
Serotonergic signaling plays a deeply conserved role in improving oocyte quality
Authors: Aprison Erin Z. , Dzitoyeva Svetlana , Ruvinsky Ilya
Published: March 2023

Abstract

Declining germline quality is a major cause of reproductive senescence. Potential remedies could be found by studying regulatory pathways that promote germline quality. Several lines of evidence, including aC. elegansmale pheromone ascr#10 that counteracts the effects of germline aging in hermaphrodites, suggest that the nervous system plays an important role in regulating germline quality. Inspired by the fact that serotonin mediates ascr#10 signaling, here we show that serotonin reuptake inhibitors recapitulate the effects of ascr#10 on the germline and promote healthy oocyte aging inC. elegans. Surprisingly, we found that pharmacological increase of serotonin signaling stimulates several developmental processes inD. melanogaster, including improved oocyte quality, although underlying mechanisms appear to be different between worms and flies. Our results reveal a plausibly conserved role for serotonin in maintaining germline quality and identify a class of therapeutic interventions using available compounds that could efficiently forestall reproductive aging.
The importance of identifying red flags in wrist and hand pain: a scoping review protocol
Authors: Rossi Federico , Cordella Marco , Lanfranchi Elena , Marca Roberta La , Mennea Ruggero , Pierazzoli Daniele , Cioeta Matteo , Pellicciari Leonardo
Published: March 2023

Background

Musculoskeletal pain can be defined as a consequence of a trauma or as a disorder of varying nature, which can be manifested in bones, muscles, tendinous and ligamentous structures, including those of the wrist and hand. However, such pain can mimic pathologies that need further diagnostic investigations; as a consequence, healthcare practitioners have to be able to detect their signs and symptoms, in order to refer the patient to the most appropriate clinician.

The current literature lacks of reviews that analyze red flags in the field of wrist and hand pain. The reviewers would like to look for any correlations that could be useful in a correct screening process by clinicians.

Methods

This scoping review will be performed in accordance with the PRISMA extensions for Scoping Reviews (PRISMA-ScR). Studies will be included if they meet the following inclusion criteria: population characterized by wrist and hand pain with or without comorbidities either at the present or in the past. No limits of age, gender and sport activity will be applied. No study design, publication type, and data restrictions will be applied. MEDLINE, Web of Science, Cochrane Library, CINAHL, Embase, PEDro databases will be searched up to February 2023. Two reviewers will independently screen all title, abstracts and full-text studies for inclusion. A data collection form will be developed by the research team to extract the characteristics of the studies included. A tabular and accompanying narrative summary of the information will be provided.

Conclusions

This will be the first scoping review to provide a comprehensive overview of the topic. The results will add meaningful information for future research and clinical practice. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
The relationship between musicianship and pain. Is chronic pain and its management a problem for student musicians only?
Authors: Korte Michaela , Cerci Deniz , Wehry Roman , Timmers Renee , Williamson Victoria J.
Published: March 2023

Neuro-biological research into chronic pain has presented reliable evidence of distinct cortical and spinal alterations in chronic pain sufferers compared to healthy individuals. Furthermore, research suggests that musicians are especially vulnerable to frequent and extended pain, supported by recent neurological investigations into musicians’ brain plasticity. However, chronic pain is not simply acute pain plus time, but a separate condition. Little is known about musicians’ emotions and chronic pain-related behaviors. Acquiring such knowledge is a crucial step in understanding how chronic pain is processed by musicians. This study investigated pain catastrophizing as one of the pain-related behaviors and emotions alongside six complementary variables: anxiety, depression, depersonalization, burnout, coping strategies and professional identity. 102 under- and postgraduate students from various higher education institutions participated in an online survey. Students were allocated to three groups according to their main study subject and type of institution: music college musicians, university musicians and university non-musicians. Group testing showed that university non-musicians’ pain catastrophizing was significantly worse compared to music college musicians.

Music college musicians and university musicians were less prone to maladaptive pain processes, despite perceiving pain for significantly longer periods of time. This novel finding indicates that chronic pain does not inevitably lead to dysfunctional pain processing for musicians and should be reflected accordingly in order to optimize pain-control. The bio-psycho-socio model of chronic pain provides the most robust framework for future research, with the aim of improving care and wellbeing provision for the management of chronic pain in musicians.
Suitability of Machine Learning for Atrophy and Fibrosis Development in Neovascular Age-Related Macular Degeneration
Authors: de la Fuente Jesus , Llorente-González Sara , Fernandez-Robredo Patricia , Hernandez María , García-Layana Alfredo , Ochoa Idoia , Recalde Sergio ,   Spanish AMD group
Published: March 2023

Anti-VEGF therapy has reduced the risk of legal blindness on neovascular age-related macular degeneration (nAMD), but still several patients develop fibrosis or atrophy in the long-term. Although recent statistical analyses have associated genetic, clinical and imaging biomarkers with the prognosis of patients with nAMD, no studies on the suitability of machine learning (ML) techniques have been conducted. We perform an extensive analysis on the use of ML to predict fibrosis and atrophy development on nAMD patients at 36 months from start of anti-VEGF treatment, using only data from the first 12 months. We use data collected according to real-world practice, which includes clinical and genetic factors. The ML analysis consistently found ETDRS to be relevant for the prediction of atrophy and fibrosis, confirming previous statistical analyses, while genetic variables did not show statistical relevance. The analysis also reveals that predicting one macular degeneration is a complex task given the available data, obtaining in the best case a balance accuracy of 63% and an AUC of 0.72. The lessons learnt during the development of this work can guide future ML-based prediction tasks within the ophthalmology field and help design the data collection process.
CD32 allows capturing blood cells emergence in slow motion during human embryonic development
Authors: Scarfò Rebecca , Alezz Monah Abou , El Khoury Mahassen , Gersch Amélie , Li Zhong-Yin , Luff Stephanie A. , Valsoni Sara , Cascione Sara , Didelon Emma , Merelli Ivan , Freund Jean-Noël , Sturgeon Christopher M. , Tavian Manuela , Ditadi Andrea
Published: March 2023

During development, in the embryo proper blood cells emerge from a subset of specialized endothelial cells, named hemogenic endothelial cells (HECs), via a process known as endothelial-to-hematopoietic transition (EHT) driven by time-specific Notch signaling activation1. HECs represent an elusive cell population as they are rare and transient, rapidly generating blood cells, and specific markers are lacking. Therefore, it remains unclear how and when the hematopoietic fate is specified and how blood cell emergence is molecularly regulated. Notably, thorough characterization of this process is essential to guide the generation of therapeutic blood productsin vitrofrom human pluripotent stem cells (hPSCs). To identify specific human HEC markers, we performed transcriptomic analysis of 28-32-day human embryos, a developmental stage characterized by active hematopoiesis. We observed that the expression ofFCGR2B, encoding for the Fc receptor CD32, is highly enriched in the ACE+CD34+endothelial cell population that contains HECs. Functionalex vivoanalyses confirmed that multilineage hematopoietic potential is highly enriched in CD32+endothelial cells isolated from human embryos. In addition, clonal analysis revealed that 90% of CD32+hPSC-derived endothelial cells arebona fideHECs. We leveraged this specificity to study how HECs commit to the blood fate. Remarkably, our analyses indicated that HECs progress through different states culminating with the one identified by CD32 expression. Indeed CD32+HECs no longer require Notch to generate hematopoietic progeny and display full commitment to hematopoiesis even before the expression of hematopoietic markers. These findings provide a precise method for isolating HECs primed to the blood fate from human embryos and hPSC cultures, thus allowing the efficient generation of hematopoietic cellsin vitro.
Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin
Authors: Price Tara R. , Stapleton Donnie S. , Schueler Kathryn L. , Norris Marie K. , Parks Brian W. , Yandell Brian S. , Churchill Gary A. , Holland William L. , Keller Mark P. , Attie Alan D.
Published: March 2023

We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion ofAbhd2. TheAbhd2KOmice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in maleAbhd2KOmice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.
An Arm-to-Disarm Strategy to Overcome Phenotypic AMR inMycobacterium tuberculosis
Authors: Kumar T. Anand , Birua Shalini , Chandra M. Sharath , Mukherjee Piyali , Singh Samsher , Kaul Grace , Akhir Abdul , Chopra Sidharth , Hirschi Jennifer , Singh Amit , Chakrapani Harinath
Published: March 2023

Most front-line tuberculosis drugs are ineffective against hypoxic non-replicating drug-tolerantMycobacterium tuberculosis(Mtb) contributing to phenotypic antimicrobial resistance (AMR). This is largely due to the poor permeability in the thick and waxy cell wall of persister cells, leading to diminished drug accumulation and reduced drug-target engagement. Here, using an “arm-to-disarm” prodrug approach, we demonstrate that non-replicatingMtbpersisters can be sensitized to Moxifloxacin (MXF), a front-line TB drug. We design and develop a series of nitroheteroaryl MXF prodrugs that are substrates for bacterial nitroreductases (NTR), a class of enzymes that are over-expressed in hypoxicMtb. Enzymatic activation involves electron-transfer to the nitroheteroaryl compound followed by protonation via water that contributes to the rapid cleavage rate of the protective group by NTR to produce the active drug. Phenotypic and genotypic data are fully consistent with MXF-driven lethality of the prodrug inMtbwith the protective group being a relatively innocuous bystander. The prodrug increased intracellular concentrations of MXF than MXF alone and is more lethal than MXF in non-replicating persisters. Hence, arming drugs to improve permeability, accumulation and drug-target engagement is a new therapeutic paradigm to disarm phenotypic AMR.
Phosphoregulation of the Rad51 auxiliary factor Swi5-Sfr1
Authors: Liang Pengtao , Lister Katie , Yates Luke , Argunhan Bilge , Zhang Xiaodong
Published: March 2023

Homologous recombination (HR) is a major pathway for the repair of DNA double-strand breaks, the most severe form of DNA damage. The Rad51 protein is central to HR, but multiple auxiliary factors regulate its activity. The heterodimeric Swi5-Sfr1 complex is one such factor. It was previously shown that two sites within the intrinsically disordered domain of Sfr1 are critical for the interaction with Rad51. Here, we show that phosphorylation of five residues within this domain regulates the interaction of Swi5-Sfr1 with Rad51. Biochemical reconstitutions demonstrated that a phosphomimetic mutant version of Swi5-Sfr1 is defective in both the physical and functional interaction with Rad51. This translated to a defect in DNA repair, with the phosphomimetic mutant yeast strain phenocopying the previously established interaction mutant. Interestingly, a strain in which Sfr1 phosphorylation was blocked also displayed sensitivity to DNA damage. Taken together, we propose that controlled phosphorylation of Sfr1 is important for the role of Swi5-Sfr1 in promoting Rad51-dependent DNA repair.
Adverse outcomes in SARS-CoV-2 infected pregnant mice are gestational age-dependent and resolve with antiviral treatment
Authors: Creisher Patrick S. , Perry Jamie L. , Zhong Weizhi , Lei Jun , Mulka Kathleen R , Ryan Hurley , Zhou Ruifeng , Akin Elgin H. , Liu Anguo , Mitzner Wayne , Burd Irina , Pekosz Andrew , Klein Sabra L.
Published: March 2023

SARS-CoV-2 infection during pregnancy is associated with severe COVID-19 and adverse fetal outcomes, but the underlying mechanisms remain poorly understood. Moreover, clinical studies assessing therapeutics against SARS-CoV-2 in pregnancy are limited. To address these gaps, we developed a mouse model of SARS-CoV-2 infection during pregnancy. Outbred CD1 mice were infected at embryonic day (E) 6, E10, or E16 with a mouse adapted SARS-CoV-2 (maSCV2) virus. Outcomes were gestational age-dependent, with greater morbidity, reduced anti-viral immunity, greater viral titers, and more adverse fetal outcomes occurring with infection at E16 (3rdtrimester-equivalent) than with infection at either E6 (1sttrimester-equivalent) or E10 (2ndtrimester-equivalent). To assess the efficacy of ritonavir-boosted nirmatrelvir (recommended for pregnant individuals with COVID-19), we treated E16-infected dams with mouse equivalent doses of nirmatrelvir and ritonavir. Treatment reduced pulmonary viral titers, decreased maternal morbidity, and prevented adverse offspring outcomes. Our results highlight that severe COVID-19 during pregnancy and adverse fetal outcomes are associated with heightened virus replication in maternal lungs. Ritonavir-boosted nirmatrelvir mitigated adverse maternal and fetal outcomes of SARS-CoV-2 infection. These findings prompt the need for further consideration of pregnancy in preclinical and clinical studies of therapeutics against viral infections.
Single-cell mRNA-regulation analysis reveals cell type-specific mechanisms of type 2 diabetes
Authors: Martínez-López J.A. , Lindqvist A. , Lopez-Pascual A. , Chen P. , Shcherbina L. , Chriett S. , Skene N.G. , Prasad R.B. , Lancien M. , Johnson P.F. , Eliasson P. , Louvet C. , Muñoz-Manchado A.B. , Sandberg R. , Hjerling-Leffler J. , Wierup N.
Published: March 2023

Perturbed secretion of insulin and other pancreatic islet hormones is the main cause of type 2 diabetes (T2D). The islets harbor five cell types that are potentially altered differently by T2D. Whole-islet transcriptomics and single-cell RNA-sequencing (scRNAseq) studies have revealed differentially expressed genes without reaching consensus. Here, we demonstrate that unprecedented insights into disease mechanisms can be obtained by network-based analysis of scRNAseq data. We developed differential gene coordination network analysis (dGCNA) and analyzed islet scRNAseq data from 16 T2D and 16 non-T2D individuals. dGCNA revealed T2D-induced cell type-specific networks of dysregulated genes with remarkable ontological specificity, thus allowing for a comprehensive and unbiased functional classification of genes involved in T2D. In beta cells eleven networks of genes were detected, revealing that mitochondrial electron transport chain, glycolysis, cytoskeleton organization, cell proliferation, unfolded protein response and three networks of beta cell transcription factors are perturbed, whereas exocytosis, lysosomal regulation and insulin translation programs are instead enhanced in T2D. Furthermore, we validated the ability of dGCNA to reveal disease mechanisms and predict the functional context of genes by showing thatTMEM176A/Bregulates the beta cell cytoskeleton and thatCEPBGis a key regulator of the unfolded protein response. In addition, comparing beta- and alpha and cells, we found substantial differences, reproduced across independent datasets, confirming cell type-specific alterations in T2D. We conclude that analysis of networks of differentially coordinated genes provides outstanding insight into cell type-specific gene function and T2D pathophysiology.
Boris Gruber's contributions to mathematical crystallography
Authors: Grimmer Hans
Published: March 2023

Boris Gruber made fundamental contributions to the study of crystal lattices, leading to a finer classification of lattice types than those of Paul Niggli and Boris Delaunay before him.
NPOs and private governance forms for football clubs: towards a blended model
Authors: Agostino Deborah , Thomasson Anna
Published: March 2023

Purpose

This study explores the relationship between governance model – private organisations vs non-profit organisations (NPOs) – and performance in football clubs.

Design/methodology/approach

The study is a comparative case study of two football clubs with different governance models: Malmö FF, which is an NPO, and Bologna FC, which is a privately owned club.

Findings

The results show that both football clubs focus equally on financial and non-financial performance, and in practice, both clubs use a blend of private and NPO governance models. While supporting efforts towards financial results, blending the models appears to support football clubs' management of the tension between financial and non-financial performance and the expectation that they will contribute to local development. Thus, using a blend of the two models is not only accepted but expected.

Research limitations/implications

This study is a comparative case study of two football clubs. This study furthers our understanding of how football clubs manage the tension between financial and non-financial performance expectations. This is particularly of interest in light of the increasing professionalisation of sports, especially football, and how this might jeopardise the contributions that sport clubs make to the local community.

Originality/value

By exploring the relationship between governance model and performance, this study shows that, contrary to expectations, privately owned football clubs focus as much on non-financial performance as clubs governed as NPOs. This study contributes to the existing literature by showing how clubs use a mixture of elements from governance models to manage the tension between financial and non-financial performance that has emerged in the wake of the increasing professionalisation of football.
Enhanced WPT structures via EC-SRR-based metasurfaces
Authors: Karatzidis Dimitrios I. , Zygiridis Theodoros T. , Kantartzis Nikolaos V.
Published: March 2023

Purpose

The purpose of this paper is to present a family of robust metasurface-oriented wireless power transfer systems with improved efficiency and size compactness. The effect of geometric and structural features on the overall efficiency and miniaturisation is elaborately studied, while the presence of substrate losses is, also, considered. Moreover, to further enhance the performance, possible means for reducing the operating frequency, without comprising the unit-cell size, are proposed.

Design/methodology/approach

The key element of the design technique is the edge-coupled split-ring resonators patterned in various metasurface configurations and optimally placed to increase the total efficiency. To this goal, a rigorous three-dimensional algorithm, launching a new high-order prism macroelement, is developed in this paper for the fast evaluation of the required quantities. The featured scheme can host diverse approximation orders, while it is drastically more economical than existing methods. Hence, the demanding wireless power transfer systems are precisely modelled via reduced degrees of freedom, without the need to conduct large-scale simulations.

Findings

Numerical results, compared with measured data from fabricated prototypes, validate the design methodology and prove its competence to provide enhanced metasurface wireless power transfer systems. An assortment of optimized 3 x 3 and 5 x 5 metamaterial setups is investigated, and interesting deductions, regarding the impact of the inter-element gaps, the distance between the transmitting and receiving components and the substrate losses, are derived. Also, the proposed vector macroelement technique overwhelms typical implementations in terms of computational burden, particularly when combined with the relevant commercial software packages.

Originality/value

Systematic design of advanced real-world wireless power transfer structures through optimally selected metasurfaces with fully controllable electromagnetic properties is presented. The analysis is performed by means of a rapid prism macroelement methodology, which leads to very confined meshes, accurate results and significantly reduced overhead. The selected metamaterial resonators are found to be very flexible and reconfigurable, even in the case of large substrate conductivity losses, whereas their contribution to the system’s total efficiency is decisive.
Predicting song genre with deep learning
Authors: Marijić Antonijo , Bagić Babac Marina
Published: March 2023

Purpose

Genre classification of songs based on lyrics is a challenging task even for humans, however, state-of-the-art natural language processing has recently offered advanced solutions to this task. The purpose of this study is to advance the understanding and application of natural language processing and deep learning in the domain of music genre classification, while also contributing to the broader themes of global knowledge and communication, and sustainable preservation of cultural heritage.

Design/methodology/approach

The main contribution of this study is the development and evaluation of various machine and deep learning models for song genre classification. Additionally, we investigated the effect of different word embeddings, including Global Vectors for Word Representation (GloVe) and Word2Vec, on the classification performance. The tested models range from benchmarks such as logistic regression, support vector machine and random forest, to more complex neural network architectures and transformer-based models, such as recurrent neural network, long short-term memory, bidirectional long short-term memory and bidirectional encoder representations from transformers (BERT).

Findings

The authors conducted experiments on both English and multilingual data sets for genre classification. The results show that the BERT model achieved the best accuracy on the English data set, whereas cross-lingual language model pretraining based on RoBERTa (XLM-RoBERTa) performed the best on the multilingual data set. This study found that songs in the metal genre were the most accurately labeled, as their text style and topics were the most distinct from other genres. On the contrary, songs from the pop and rock genres were more challenging to differentiate. This study also compared the impact of different word embeddings on the classification task and found that models with GloVe word embeddings outperformed Word2Vec and the learning embedding layer.

Originality/value

This study presents the implementation, testing and comparison of various machine and deep learning models for genre classification. The results demonstrate that transformer models, including BERT, robustly optimized BERT pretraining approach, distilled bidirectional encoder representations from transformers, bidirectional and auto-regressive transformers and XLM-RoBERTa, outperformed other models.
Study of flow field and vibration characteristics of supersonic centrifugal impellers based on fluid-structure interaction
Authors: Li Huanjun , Zhang Yimin
Published: March 2023

Purpose

There are three purposes in this paper: to verify the importance of bi-directional fluid-structure interaction algorithm for centrifugal impeller designs; to study the relationship between the flow inside the impeller and the vibration of the blade; study the influence of material properties on flow field and vibration of centrifugal blades.

Design/methodology/approach

First, a bi-directional fluid-structure coupling finite element numerical model of the supersonic semi-open centrifugal impeller is established based on the Workbench platform. Then, the calculation results of impeller polytropic efficiency and stage total pressure ratio are compared with the experimental results from the available literature. Finally, the flow field and vibrational characteristics of 17-4PH (PHB), aluminum alloy (AAL) and carbon fiber-reinforced plastic (CFP) blades are compared under different operating conditions.

Findings

The results show that the flow fields performance and blade vibration influence each other. The flow fields performance and vibration resistance of CFP blades are higher than those of 17-4PH (PHB) and aluminum alloy (AAL) blades. At the design speed, compared with the PHB blades and AAL blades, the CFP blades deformation is reduced by 34.5% and 9%, the stress is reduced by 69.6% and 20% and the impeller pressure ratio is increased by 0.8% and 0.14%, respectively.

Originality/value

The importance of fluid-structure interaction to the aerodynamic and structural design of centrifugal impeller is revealed, and the superiority over composite materials in the application of centrifugal impeller is verified.
Board characteristics and corporate cash holding: evidence from the UK, France and Germany
Authors: Ezeani Ernest , Salem Rami Ibrahim A. , Usman Muhammad , Kwabi Frank , Bilal
Published: March 2023

Purpose

Prior studies suggest that corporate cash holding will reflect firms' corporate governance (CG) environment. Consistent with this prediction, this study aims to examine the impact of board characteristics on firms' cash holding in the UK, France and Germany.

Design/methodology/approach

Using 2,805 firm-year observations between 2009 and 2019, the authors examine the relationship between board characteristics and corporate cash holding. The authors used two measures of cash holdings as our dependent variables. As independent variables, the authors used CG characteristics relevant to effective board monitoring such as board meetings, outside directors, board size and board gender diversity.

Findings

The authors find that board characteristics influence firms' cash holdings of firms in the UK, France and Germany. However, this study documents evidence of varying impacts of board monitoring on the cash holding of the UK when compared to German and French firms, the countries that are classifiable as bank-based economies. The result of this study is robust to alternative cash-holding measures and endogeneity.

Practical implications

This study provides evidence supporting the board's impact in mitigating agency conflict in shareholder- and stakeholder-oriented CG environments.

Originality/value

This study contributes to previous works on firms’ financial orientation by showing that the impact of board characteristics on corporate cash holdings varies between bank- and market-based economies.
The relationship between income smoothing and the cost of debt: evidence from the United Kingdom and Nigeria
Authors: Aboud Ahmed , Haruna Baba , Diab Ahmed
Published: March 2023

Purpose

This paper aims to examine the association between income smoothing and the cost of debt in two different countries, namely, the UK and Nigeria.

Design/methodology/approach

The authors used a sample from listed firms in the UK and Nigeria during 2000–2019. The study hypotheses are examined by implementing quantitative methods, including panel regression analysis, cross-sectional regression analysis and parametric independent samples t-test.

Findings

The results reveal that Nigerian companies have a substantially higher cost of debt and are more active in using income-smoothing practices. However, the relationship between income smoothing and the cost of debt is not found to be statistically significant in both countries. Besides, the results of this study show that financial leverage, profitability, company size and asset turnover are significantly associated with the cost of debt.

Originality/value

The study contributes to the existing literature by providing new insights concerning the contrast between developed and developing countries in financial and reporting issues.
The interaction effect of trust and contract on dispute negotiation strategy: evidence from the Chinese construction industry
Authors: FU Yafan , Luo Yangyang
Published: March 2023

Purpose

This paper aims to investigate how and when different dimensions of trust and contracts interact to influence the development to negotiation strategies. Specifically, it explores how different dimensions of trust and contracts are combined to influence dispute negotiation strategies when cooperation parties have or do not have expectations of continuity.

Design/methodology/approach

This paper theoretically identified and empirically examined the interaction effect of trust and contract on dispute negotiation strategies in contractor–subcontractor relationships, by developing a conceptual framework and conducting a questionnaire survey comprising more than 300 disputes in the Chinese construction industry. Hierarchical regression analysis was mainly used to test the hypotheses.

Findings

This paper finds that contractual control may weaken the effect of goodwill trust in fostering interest-based strategies in the presence of expectations of continuity, while it may strengthen the effect in the absence of expectations of continuity. Contractual coordination negatively moderates the relationship between goodwill trust and interest-based strategies only when parties have little expectations of continuity. Moreover, contractual control enhances the effectiveness of competence trust on fostering interest-based strategies.

Practical implications

This paper provides insights for practitioners to wisely use different governance mechanisms to manage negotiation strategies and generate desired outcomes of dispute resolution.

Originality/value

This paper provides a nuanced understanding of how the two types of governance mechanisms interact, by considering trust and contract as multi-dimensional constructs. It explicit the boundary conditions of both the substitute and complementary relationship between them.
A model of financial support for the poor to access health services in Iran: Delphi technique
Authors: Etemadi Manal , Ashtarian Kioomars , Ganji Nader
Published: March 2023

Purpose

Reducing inequity in health between the poor and the rich is one of the challenges of the Iranian health sector. Access to health services in Iran is lower in the lowest-income quarter, and the rich use health services more. The purpose of this study is to provide a comprehensive framework for enabling financial access by the poor to health services in Iran.

Design/methodology/approach

Policy options were validated and approved by experts and specialists in two stages using the Delphi technique. The sample was consisted of 22 well-known experts on the subject who were selected based on purposive sampling. To evaluate the reliability of the questionnaire, a pilot study was conducted with five participants. Dimensional validity of the policy model, which was agreed upon by more than 75% of the participants was acceptable.

Findings

The main aspects of the model were divided into five categories: identifying the poor, policymaking to prevent the aggravation of health poverty, providing targeted funding, highlighting the importance of coherent regulation and ensuring financial accessibility to health services for the poor. This model could align the activities of all stakeholders in the form of a network and considers its prerequisites.

Originality/value

Prevention of dire financial consequences in the case of referral to follow up the treatment alongside exemption and financial protection policies through the networking activities of organizations involved in this field is a crucial step in securing financial support for the poor. Although the researchers included a wide range of policymakers in the Delphi study to gather all perspectives about options for financially support the poor, there may be some potential neglected policy advices.