bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune priming prior to pathogen exposure sheds light on the relationship between host, microbiome and pathogen in disease
Authors: Kaganer Alyssa W. , Ossiboff Robert J. , Keith Nicole I. , Schuler Krysten L. , Comizzoli Pierre , Hare Matthew P. , Fleischer Robert C. , Gratwicke Brian , Bunting Elizabeth M.
Published: February 2023

Dynamic interactions between host, pathogen and host-associated microbiome dictate infection outcomes. Pathogens includingBatrachochytrium dendrobatidis(Bd) threaten global biodiversity, but conservation efforts are hindered by limited understanding of amphibian host, Bd and microbiome interactions. We conducted a vaccination and infection experiment using Eastern hellbender salamanders (Cryptobranchus alleganiensis alleganiensis) challenged with Bd to observe infection, skin microbial communities and gene expression of host skin, pathogen and microbiome throughout the experiment. Most animals survived high Bd loads regardless of their vaccination status and vaccination did not affect pathogen load, but host gene expression differed based on vaccination. Oral vaccination (exposure to killed Bd) stimulated immune gene upregulation while topically and sham-vaccinated animals did not significantly upregulate immune genes. In early infection, topically vaccinated animals upregulated immune genes but orally and sham-vaccinated animals downregulated immune genes. Bd increased pathogenicity-associated gene expression in late infection when Bd loads were highest. The microbiome was altered by Bd, but there was no correlation between anti-Bd microbe abundance or richness and pathogen burden. Our observations suggest that hellbenders initially generate a vigorous immune response to Bd, which is ineffective at controlling disease and is subsequently modulated. Interactions with antifungal skin microbiota did not influence disease progression.
Monitoring and Tracking the Spread of SARS-CoV-2 in Asturias, Spain
Authors: Gonzalez-Alba Jose Maria , Rojo-Alba Susana , Perez-Martinez Zulema , Boga Jose A. , Alvarez-Arguelles Marta Elena , Gomez Juan , Herrero Pablo , Costales Isabel , Alba Luz Maria , Martin-Rodriguez Gabriel , Campo Rainer , Castelló-Abietar Cristian , Sandoval Marta , Abreu-Salinas Fátima , Coto Eliecer , Rodriguez Mercedes , Rubianes Pablo , Sanchez Maria Luisa , Vazquez Fernando , Antuña Luis , Álvarez Victoria , Melón García Santiago
Published: February 2023

Mutational analysis of SARS-CoV-2 can quantify their relative importance over time, enable the dominant mutations to be identified and facilitate near real-time detection, comparison, and tracking of evolving variants. Collected samples in Asturias an autonomous community of Spain with a large aged population, and high levels of migration and tourism was monitored and tracked from its beginning in February 2020 until its decline and stabilization in August 2021, were characterized using whole genomic sequence and single nucleotide polymorphism. Data held in the GISAID database was analyzed to establish patterns in the appearance and persistence of SARS-CoV-2 strains. Only 138 non-synonymous mutations occurring in more than 1% of the population of SARS-CoV-2 were found, identifying 10 major variants worldwide (7 arose before January 2021), 19 regional and 1 local. In Asturias only 17 different variants were found. After vaccination, no further regional majority variants were found. Only half of the defined variants circulated and no new variants were generated, indicating that infection control measures (fast diagnosis, prevention measures and vaccination) were efficient.
Bacteremia and obstructive pyelonephritis caused by Bifidobacterium breve in an elderly woman: A case report and literature review
Authors: Nishio Mitsuru , Morioka Hiroshi , Takai Shun , Seki Yoshie , Osugi Takato , Oba Airi , Miyaki Yuki
Published: February 2023

An 83-year-old woman taking cephalexin for 4 days was diagnosed with obstructive pyelonephritis. Bifidobacterium breve was isolated from anaerobic and aerobic blood culture bottles and an anaerobic urine culture. Urinary tract infection caused by Bifidobacterium spp. can develop in patients with underlying urological conditions.
Geotemporal analysis of COVID-19 in the Dominican Republic 2020-2021
Authors: Moreno Andreina , Gonzalez Carla , Pimentel Lilian , Herrera Demián , Colomé Manuel
Published: February 2023

Introduction

Coronavirus disease (COVID-19) was first identified in China in December of 2019 and has spread globally since. The Dominican Republic confirmed its first case on March 1st, 2020.

Objective

To analyze the spatial distribution of the incidence of COVID-19 and its correlation with the Human Development Index in the Dominican Republic from March of 2020 to March of 2021.

Methods

The cumulative incidence rates of COVID-19, number of deaths, lethality, mortality and Human Development Index of the provinces in the Dominican Republic were used from governmental sources and were analyzed in the Microsoft Excel 2016 program.

Results

Duarte was the province with the highest mortality per 100.000 inhabitants (68.94), followed by the Distrito Nacional (71,613 cases), Santo Domingo (49,759 cases) and Santiago (27,632 cases) with the highest number of cases. The 7-day moving average peak for new cases was July 30 of 2020 and the peak for new deaths occurred on September 6 of 2020. The highest positivity rate (40%) was reported in August of 2020. Lastly, an increase of 1.0 on the Human Development Index corresponded to a 10.7% increase in the incidence rates per province.

Conclusion

Prevention strategies should be strengthened by the Dominican government to reduce the contagion curve and thus reduce its spread and impact on the Human Development Index
Microglial phagocytosis mediates long-term restructuring of spinal GABAergic circuits following early life injury
Authors: Xu Yajing , Moulding Dale , Jin Wenanlan , Beggs Simon
Published: February 2023

Peripheral injury during the early postnatal period alters the somatosensory system, leading to behavioural hyperalgesia upon re-injury in adulthood. Spinal microglia have been implicated as the cellular mediators of this phenomenon, but the mechanism is unclear. We hypothesised that neonatal injury (1) alters microglial phagocytosis of synapses in the dorsal horn leading to long-term structural changes in neurons, and/or (2) trains microglia, leading to a stronger microglial response after re-injury in adulthood. Using hindpaw surgical incision as a model we showed that microglial density and phagocytosis increased in the dorsal horn region innervated by the hindpaw. Dorsal horn microglia increased engulfment of synapses following injury, with a preference for those expressing the vesicular GABA transporter VGAT and primary afferent A-fibre terminals in neonates. This led to a long-term reduction of VGAT density in the dorsal horn and reduced microglial phagocytosis of VGLUT2 terminals. We also saw an increase in apoptosis following neonatal injury, which was not limited to the dorsal horn suggesting that larger circuit wide changes are happening.

In adults, hindpaw incision increased microglial engulfment of predominantly VGAT synapses but did not alter the engulfment of A-fibres. This engulfment was not affected by prior neonatal injury, suggesting that microglial phagocytosis was not trained. These results highlight microglial phagocytosis in the dorsal horn as an important physiological response towards peripheral injury with potential long-term consequences and reveals differences in microglial responses between neonates and adults.
Current Status and Emerging Trends of COVID-19-related Studies in Seven ‘Tropical Medicine’-entitled Journals
Authors: Zhang Xuejuan , Zhong Ziqiao , Luo Peili , Zhu Chune , Huang Ying , Wu Chuanbin , Pan Xin , Huang Zhengwei
Published: February 2023

Background

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created enormous medical and economic burdens on human society. However, the co-existence of COVID-19 and diseases in tropical regions is not taken seriously. To improve the understanding of the current status and trends on crosstalk of COVID-19 and tropical diseases, this paper provided an analysis, from a bibliometric perspective, of the COVID-19-related publications in ‘Tropical Medicine’-entitled journals.

Methods

We used Clarivate Analytics and VOSviewer to analyze 783 publications in seven ‘Tropical Medicine’-entitled journals. Document overview, basic bibliometric characteristics, citation performance, co-authorship, co-citation, bibliographic coupling, and co-occurrence of keywords and terms were summarized in this article.

Results

Document overview revealed that 76.12% of the related publications were published in open access mode, and basic bibliometric characteristics indicated that the year 2021 was the peak of the number of publications, the documents in the seven journals were unevenly distributed, and ‘article’ was the main publication type. The citation performance analysis elucidated that the documents of interest were frequently cited. The co-authorship analysis showed cooperation networks on the level of region, organization and author. General knowledge of COVID-19 was the overlap of co-citation and bibliographic coupling behavior. Finally, the co-occurrence of keywords and terms revealed the current and emerging hotspots.

Conclusions

The main current research focuses in ‘Tropical Medicine’-entitled journals are the clinical features of COVID-19 patients, and the emerging trends are the hesitancy in making vaccines against SARS-CoV-2 and the circumstance where COVID-19 coexisted with tropical diseases. In summary, this bibliometric analysis of COVID-19-related studies in seven ‘Tropical Medicine’-entitled journals highlights the current research focuses of this field to inspire future studies.
Differentiable Partition Function Calculation for RNA
Authors: Matthies Marco , Krueger Ryan , Torda Andrew , Ward Max
Published: February 2023

Abstract

Ribonucleic acid (RNA) is an essential molecule in a wide range of biological functions. In 1990, McCaskill introduced a dynamic programming algorithm for computing the partition function of an RNA sequence. This forward model is widely used for understanding the thermodynamic properties of a given RNA. In this work, we introduce a generalization of McCaskill’s algorithm that is well-defined over continuous inputs and is differentiable. This allows us to tackle the inverse folding problem—designing a sequence with desired equilibrium thermodynamic properties—directly using gradient optimization. This has applications to creating RNA-based drugs such as mRNA vaccines. Furthermore, it allows McCaskill’s foundational algorithm to be incorporated into machine learning pipelines directly since we have made it end-to-end differentiable. This work highlights how principles from differentiable programming can be translated to existing physical models to develop powerful tools for machine learning. We provide a concrete example by implementing an effective and interpretable RNA design algorithm.
Tregs constrain CD8+T cell priming required for curative intratumorally anchored anti-4-1BB immunotherapy
Authors: Palmeri Joseph R. , Lax Brianna M. , Peters Joshua M. , Duhamel Lauren , Stinson Jordan A. , Santollani Luciano , Lutz Emi A. , Pinney William , Bryson Bryan D. , Wittrup K. Dane
Published: February 2023

Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical development has been hampered by on-target, off-tumor toxicity. Here, we report the development of a tumor-anchored α4-1BB agonist (α4-1BB-LAIR), which consists of an α4-1BB antibody fused to the collagen binding protein LAIR. While combination treatment with an antitumor antibody (TA99) displayed only modest efficacy, simultaneous depletion of CD4+T cells boosted cure rates to over 90% of mice. We elucidated two mechanisms of action for this synergy: αCD4 eliminated tumor draining lymph node Tregs, enhancing priming and activation of CD8+T cells, and TA99 + α4-1BB-LAIR supported the cytotoxic program of these newly primed CD8+T cells within the tumor microenvironment. Replacement of αCD4 with αCTLA-4, a clinically approved antibody that enhances T cell priming, produced equivalent cure rates while additionally generating robust immunological memory against secondary tumor rechallenge.

One Sentence Summary

Inhibition of nodal Tregs enhances CD8+T cell priming, improving antitumor responses to collagen-anchored α4-1BB combination therapy.
Fully accessible fitness landscape of oncogene-negative lung adenocarcinoma
Authors: Yousefi Maryam , Andrejka Laura , Winslow Monte M. , Petrov Dmitri A. , Boross Gábor
Published: February 2023

Cancer genomes are almost invariably complex with genomic alterations cooperating during each step of carcinogenesis. In cancers that lack a single dominant oncogene mutation, cooperation between the inactivation of multiple tumor suppressor genes can drive tumor initiation and growth. Here, we shed light on how the sequential acquisition of genomic alterations generates oncogene-negative lung tumors. We couple tumor barcoding with combinatorial and multiplexed somatic genome editing to characterize the fitness landscapes of three tumor suppressor genes NF1, RASA1, and PTEN, the inactivation of which jointly drives oncogene-negative lung adenocarcinoma initiation and growth. The fitness landscape was surprisingly accessible, with each additional mutation leading to growth advantage. Furthermore, the fitness landscapes remained fully accessible across backgrounds with additional tumor suppressor mutations. These results suggest that while predicting cancer evolution will be challenging, acquiring the multiple alterations required for the growth of oncogene-negative tumors can be facilitated by the lack of constraints on mutational order.
Self-supervised learning for DNA sequences with circular dilated convolutional networks
Authors: Cheng Lei , Yu Tong , Aittokallio Tero , Corander Jukka , Khalitov Ruslan , Yang Zhirong
Published: February 2023

Due to their intrinsic properties, DNA molecules commonly exhibit long-range interactions along a linear sequence representation. Taking this information into account when modeling DNA sequences is therefore important for obtaining more accurate sequence-based inference. Many deep learning methods have recently been developed for this purpose, but they still suffer from two major issues. First, the existing methods can only handle short DNA fragments, thereby losing longerrange interactions. Second, the current methods require massive supervised labeling while missing most order information within the sequences. Consequently, there is a need to develop an efficient deep neural network modeling framework to extract wide contextual information for more accurate sequence-based inference tasks. Our new framework, named Revolution, takes full DNA sequences as input, without any condensation, and can give accurate predictions for DNA sequences up to 10kbp. In variant effect prediction, our method increases the Area Under the Receiver Operating Characteristics (AUROC) by 19.61% on 49 human tissues on average. Revolution is also demonstrated to work on the plant sequences by improving 2.36% AUROC on average for predicting open chromatin regions (OCRs). The data, models, and code can be freely accessed athttps://github.com/wiedersehne/Revolution-DNAPretraining.
Human pluripotent stem cell-derived respiratory airway progenitors generate alveolar epithelial cells and recapitulate features of idiopathic pulmonary fibrosis
Authors: Pezet Mikael G. , Torres Juan A. , Thimraj Tania A. , Leko Ivana Matkovic , Schrode Nadine , Murray John W. , Beaumont Kristin G. , Snoeck Hans-Willem
Published: February 2023

Human lungs contain unique cell populations in distal respiratory airways (RAs). These populations accumulate in patients with lung injury, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Their lineage potentials and roles are unknown, however. As they are absent in rodents, deeper understanding of these cells requires a humanin vitromodel. Here we report the generation from human pluripotent stem cells (hPSCs) of expandable spheres (‘induced respiratory airway progenitors’ (iRAPs)) consisting of all RA-associated cell types. iRAPs could differentiate into type 1 (AT1) and type 2 alveolar (AT2) epithelial cells in defined conditions, showing that alveolar cells can be derived from RAs. iRAPs with deletion of HPS1, which causes pulmonary fibrosis in humans, display defects that are hallmarks of IPF, indicating involvement of intrinsic dysfunction of RA-associated cells in IPF. iRAPs thus provide a model to gain insight into human lung regeneration and into pathogenesis of IPF.
Translational control offurinaby an RNA regulon is essential for heart morphogenesis and cardiac valve function
Authors: Nagorska Agnieszka , Lambert Finnlay , Inman Angus , Toral-Perez Sara , Zaucker Andreas , Gorodkin Jan , Yue Wan , Smutny Michael , Sampath Karuna
Published: February 2023

Heart development is a complex process, starting from specification of cardiac precursors and formation of a linear tube to gradual progression to a functional beating organ. For normal heart development, many processes, including asymmetric positioning of the heart along the left-right (L/R) axis, cardiac growth, and cardiac valve morphogenesis must be completed successfully. Although heart development has been studied extensively, the mechanisms that control heart morphogenesis and valve formation are not fully understood. The pro-convertase FurinA is a key protein that functions in heart development in many vertebrates including zebrafish. How FurinA activity is regulated during heart development is not known. Through computational analysis of the zebrafish transcriptome, we identified a short sequence and structure RNA motif in a variant transcript of FurinA harbouring a long 3’untranslated region (3’UTR). The alternative 3’UTRfurinaisoform is expressed at embryonic stages preceding organ positioning. Reporter localization and RNA-binding assays show that thefurina3’UTR forms complexes with the conserved RNA-binding protein and translational repressor Ybx1. Conditional mutant zebrafish embryos affectingybx1show premature and increased Furin reporter protein expression, abnormal cardiac morphogenesis and heart looping defects. Our mutantybx1hearts have an expanded atrioventricular canal, abnormal sino-atrial valves and many mutant embryos show retrograde blood flow from the ventricle to the atrium. This is similar to human heart valve regurgitation patients. Our findings show an essential function for the 3’UTR element/Ybx1 regulon in translational repression of FurinA, revealing a new upstream regulatory mechanism that controls embryonic heart development, and demonstrates theybx1mutant as a model to study cardiac valve development and function.
Mucociliary Clearance Augmenting Drugs Block SARS-Cov-2 Replication in Human Airway Epithelial Cells
Authors: Campos-Gomez Javier , Petty Courtney Fernandez , Mazur Marina , Tang Liping , Solomon George M. , Joseph Reny , Li Qian , Lever Jacelyn E. Peabody , Hussain Shah , Harrod Kevin , Onuoha Ezinwanne , Kim Harrison , Rowe Steven M.
Published: February 2023

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve barrier function of the airway epithelium, reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury, thus, it was further studied using biochemical, genetic and biophysical methods to ascertain mechanism of action via improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression and motion was required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that Intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.
Gadusol is a maternally provided sunscreen that protects fish embryos from DNA damage
Authors: Rice Marlen C. , Little Jordan H. , Forrister Dale L. , Machado Julane , Clark Nathan L. , Gagnon James A.
Published: February 2023

Ultraviolet radiation (UVR) and its deleterious effects on living cells selects for UVR-protective mechanisms. Organisms across the tree of life evolved a variety of natural sunscreens to prevent UVR-induced cellular damage and stress. However, in vertebrates, only melanin is known to act as a sunscreen. Here we demonstrate that gadusol, a transparent compound discovered over 40 years ago in fish eggs, is a maternally provided sunscreen required for survival of embryonic and larval zebrafish exposed to UVR. Mutating an enzyme involved in gadusol biosynthesis increases the formation of cyclobutane pyrimidine dimers, a hallmark of UVB-induced DNA damage. Compared to the contributions of melanin and the chorion, gadusol is the primary sunscreening mechanism in embryonic and larval fish. The gadusol biosynthetic pathway is retained in the vast majority of teleost genomes but is repeatedly lost in species whose young are no longer exposed to UVR. Our data demonstrate that gadusol is a maternally provided sunscreen that is critical for early-life survival in the most species-rich branch of the vertebrate phylogeny.
A new microphysiological system shows hypoxia primes human ISCs for interleukin-dependent rescue of stem cell activity
Authors: Rivera Kristina R. , Bliton R. Jarrett , Burclaff Joseph , Czerwinski Michael J. , Liu Jintong , Trueblood Jessica M. , Hinesley Caroline M. , Breau Keith A , Joshi Shlok , Pozdin Vladimir A. , Yao Ming , Ziegler Amanda L. , Blikslager Anthony T. , Daniele Michael A. , Magness Scott T.
Published: February 2023

Background & Aims

Hypoxia in the intestinal epithelium can be caused by acute ischemic events or conditions like Inflammatory Bowel Disease (IBD) where immune cell infiltration produces ‘inflammatory hypoxia’, a chronic condition that starves the mucosa of oxygen. Epithelial regeneration after ischemia and IBD suggests intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of acute and chronic hypoxia on human ISC (hISC) properties have not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs isolated from healthy human tissues. We then test the hypothesis that some inflammation-associated interleukins protect hISCs during prolonged hypoxia.

Methods

hISCs were exposed to <1.0% oxygen in the MPS for 6-, 24-, 48- & 72hrs. Viability, HIF1α response, transcriptomics, cell cycle dynamics, and hISC response to cytokines were evaluated.

Results

The novel MPS enables precise, real-time control and monitoring of oxygen levels at the cell surface. Under hypoxia, hISCs remain viable until 72hrs and exhibit peak HIF1α at 24hrs. hISCs lose stem cell activity at 24hrs that recovers at 48hrs of hypoxia. Hypoxia increases the proportion of hISCs in G1 and regulates hISC capacity to respond to multiple inflammatory signals. Hypoxia induces hISCs to upregulate many interleukin receptors and hISCs demonstrate hypoxia-dependent cell cycle regulation and increased organoid forming efficiency when treated with specific interleukins

Conclusions

Hypoxia primes hISCs to respond differently to interleukins than hISCs in normoxia through a transcriptional response. hISCs slow cell cycle progression and increase hISC activity when treated with hypoxia and specific interleukins. These findings have important implications for epithelial regeneration in the gut during inflammatory events.
Bacterial microbiota ofOstreobium, the coral-isolated chlorophyte ectosymbiont, at contrasted salinities
Authors: Massé A. , Detang J. , Duval C. , Duperron S. , Woo A.C. , Domart-Coulon I.
Published: February 2023

Microscopic filaments of the siphonous green algaeOstreobium(Ulvophyceae, Bryopsidales) colonize and dissolve the calcium carbonate skeletons of coral colonies, in shallow-water reef environments of contrasted salinities. Their bacterial composition and plasticity in response to salinity remain unknown. Here, we analyzed the bacteria associated with coral-isolatedOstreobiumstrains from two distinctrbcL lineages, representative of IndoPacific environmental phylotypes, that had been pre-acclimatized (>9months) to three ecologically-relevant reef salinities: 32.9, 35.1 and 40.2 psu. Bacterial phylotypes were visualized at filament scale by CARD-FISH in algal tissue sections, localized to the surface, within filaments or in the algal mucilage.Ostreobium-associated communities, characterized by bacterial 16S rRNA metabarcoding of cultured thalli and corresponding supernatants, were structured by host genotype more than salinity and partly overlapped with those of environmental (Ostreobium-colonized) coral skeletons. Alphaproteobacteria dominated the thalli communities, enriched in Kiloniellaceae or Rhodospirillaceae depending on algal genotype. A small core microbiota composed of 7 ASVs (∼1.5% of thalli ASVs, 19%-36% cumulated proportions), shared by multiple cultures of bothOstreobiumgenotypes and persistent across 3 salinities, included putative intracellular Amoebophilus and Rickettsiales bacteria. This novel knowledge on the taxonomic diversity ofOstreobiumbacterial associates paves the way to functional interaction studies within the coral holobiont.
Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures
Authors: Zhou Manqi , Zhang Hao , Bai Zilong , Mann-Krzisnik Dylan , Wang Fei , Li Yue
Published: February 2023

The advent of single-cell multi-omics sequencing technology makes it possible for re-searchers to leverage multiple modalities for individual cells and explore cell heterogeneity. However, the high dimensional, discrete, and sparse nature of the data make the downstream analysis particularly challenging. Most of the existing computational methods for single-cell data analysis are either limited to single modality or lack flexibility and interpretability. In this study, we propose an interpretable deep learning method called multi-omic embedded topic model (moETM) to effectively perform integrative analysis of high-dimensional single-cell multimodal data. moETM integrates multiple omics data via a product-of-experts in the encoder for efficient variational inference and then employs multiple linear decoders to learn the multi-omic signatures of the gene regulatory programs. Through comprehensive experiments on public single-cell transcriptome and chromatin accessibility data (i.e., scRNA+scATAC), as well as scRNA and proteomic data (i.e., CITE-seq), moETM demonstrates superior performance compared with six state-of-the-art single-cell data analysis methods on seven publicly available datasets. By applying moETM to the scRNA+scATAC data in human bone marrow mononuclear cells (BMMCs), we identified sequence motifs corresponding to the transcription factors that regulate immune gene signatures. Applying moETM analysis to CITE-seq data from the COVID-19 patients revealed not only known immune cell-type-specific signatures but also composite multi-omic biomarkers of critical conditions due to COVID-19, thus providing insights from both biological and clinical perspectives.
Bei Mu Gua Lou San facilitates mucus expectoration by increasing surface area and hydration levels of airway mucus in an air-liquid-interface cell culture model of the respiratory epithelium
Authors: Groiss Silvia , Somvilla Ina , Daxböck Christine , Stückler Manuela , Pritz Elisabeth , Brislinger Dagmar
Published: February 2023

Bei Mu Gua Lou San (BMGLS) is an ancient formulation known for its moisturizing and expectorant properties, but the underlying mechanisms remain unknown. We investigated dose-dependent effects of BMGLS on its rehydrating and mucus-modulating properties using an air-liquid-interface (ALI) cell culture model of the Calu-3 human bronchial epithelial cell line and primary normal human bronchial epithelial cells (NHBE), and specifically focused on quantity and composition of the two major mucosal proteins MUC5AC and MUC5B.

ALI cultures were treated with BMGLS at different concentrations over three weeks and evaluated by means of histology, immunostaining and electron microscopy. MUC5AC and MUC5B mRNA levels were assessed and quantified on protein level using an automated image-based approach. Additionally, expression levels of the major mucus-stimulating enzyme 15-lipoxygenase (ALOX15) were evaluated. BMGLS induced dose-dependent morphological changes in NHBE but not Calu-3 ALI cultures that resulted in increased surface area via the formation of herein termed intra-epithelial structures (IES). While cellular rates of proliferation, apoptosis or degeneration remained unaffected, BMGLS caused swelling of mucosal granules, increased the area of secreted mucus, decreased muco-glycoprotein density, and dispensed MUC5AC. Additionally, BMGLS reduced expression levels of MUC5AC, MUC5B and the mucus-stimulating enzyme 15-lipoxygenase (ALOX15).

Our studies suggest that BMGLS rehydrates airway mucus while stimulating mucus secretion by increasing surface areas and regulating goblet cell differentiation through modulating major mucus-stimulating pathways.
Detection and quantification of the histone code in the fungal genusAspergillus
Authors: Zhang Xin , Noberini Roberta , Vai Alessandro , Bonaldi Tiziana , Seidl Michael F. , Collemare Jérȏme
Published: February 2023

In eukaryotes, the combination of different histone post-translational modifications (PTMs) – the histone code – impacts the chromatin organization as compact and transcriptionally silent heterochromatin or accessible and transcriptionally active euchromatin. Although specific histone PTMs have been studied in fungi, an overview of histone PTMs and their relative abundance is still lacking. Here, we used mass spectrometry to detect and quantify histone PTMs in germinating spores of three fungal species belonging to three distinct taxonomic sections of the genusAspergillus(Aspergillus niger, Aspergillus nidulans(two strains), andAspergillus fumigatus). We overall detected 23 different histone PTMs, including a majority of lysine methylations and acetylations, and 23 co-occurrence patterns of multiple histone PTMs. Among those, we report for the first time the detection of H3K79me1/2 and H4K5/8/12ac in Aspergilli. Although all three species harbour the same PTMs, we found significant differences in the relative abundance of H3K9me1/2/3, H3K14ac, H3K36me1 and H3K79me1, as well as the co-occurrence of acetylation on both K18 and K23 of histone H3 in a strain-specific manner. Our results provide novel insights about the underexplored complexity of the histone code in filamentous fungi, and its functional implications on genome architecture and gene regulation.

Highlights

Quantitative mass spectrometry allows uncovering major histone PTMs.

H3K79me1/2 and H4K5/8/12ac are new histone PTMs detected in Aspergilli.

The relative abundance of histone PTMs varies in a strain-specific manner.

Variation in histone PTM abundance reflects different chromatin status.
Transcriptomic-based selection of reference genes for quantitative real-time PCR in an insect endosymbiotic model
Authors: Vallier Agnès , Dell’Aglio Elisa , Ferrarini Mariana Galvão , Hurtado Ophélie , Monégat Carole Vincent , Heddi Abdelaziz , Rebollo Rita , Zaidman-Rémy Anna
Published: February 2023

Reference genes are a fundamental tool for analyses of gene expression by real-time quantitative PCR (qRT-PCR), in that they ensure the correct comparison between conditions, stages, or treatments. Because of this, selection of appropriate genes to use as references is crucial for proper application of the technique. Nevertheless, efforts to find appropriate, stably expressed transcripts are still lacking, in particular in the field of insect science. Here, we took advantage of a massive transcriptomic high-throughput analysis of various developmental stages of the gut and associated-bacteriomes of the cereal weevilSitophilus oryzaeand identified a subset of stably expressed genes with the potential to be used as housekeeping genes from the larva to the adult stage. We employed several normalization techniques to select the most suitable genes among our subset. Our final selection includes three genes -TAO, YTH3andPP12A- which can also be used to compare transcript abundance at various developmental stages in symbiotic insects, and in insects devoid of endosymbionts (aposymbiotic). Since they are well conserved, these genes have the potential to be useful for many other insect species. This work confirms the interest in using large-scale, unbiased methods for reference gene selection.
Conceptual design modeling by the novel aircraft conceptual design and analysis system (ACDAS)
Authors: Ünal Nesij , Öz Yahya , Oktay Tugrul
Published: February 2023

Purpose

Throughout an aircraft development process, the conceptual design phase is an extremely important milestone; hence, the quality and success of this step directly affect the overall cost and lead time of the project. Because of this fact, the purpose of this study is to provide outputs and suggestions to the designing engineer regarding the requirements for reducing overall design time as well as costs and creating an ideal design at the early phases of the project by optimizing the aircraft development process.

Design methodology approach

The system has been prepared parametrically and presents some performance specifications for the aircraft in the early phases of the design, for example, coefficients for lift CL as well as drag CD and weight as well as fuel estimations. The software uses a combination of well-known design techniques within just one platform in contrast to many other applications. Because of this feature, it is not needed to use different sub-platforms which would require an appropriate environment and even though would lead to complications with regard to the connectivity. The system also presents relevant information about the aircraft performance like velocity versus load factor (V-n) diagrams, maximum turn rate of climb, turn rate and climb angle graphs in contrast to many other open-source conceptual design platforms.

Findings

In this study, authentic General Dynamics F-16 Fighting Falcon and McDonnell Douglas F-15 Eagle data were used as input to the system, and advanced geometric and/or performance graphs were obtained and compared to the literature where a good agreement of the results was observed. These results with regard to the aircraft performance are typically product specific and quite rare in the literature. These data obtained by use of the software during the aircraft design are, thus, of major interest, especially for the design of new aerospace platforms. In this study, all of these graphs (especially the remarkable V-n diagram) are obtained on one platform.

Originality value

The aircraft conceptual design and analysis system software provides information and suggestions regarding the requirements for reducing the overall design time, reducing the design costs and creating an optimized design at the early phases of a project by optimizing the aircraft development process within just one convenient, that is, user friendly, platform, where it uses a combination of varying methodologies. Besides presenting one interface, which is quite typical for conceptual design tools, it allows applications of methods like vortex lattices and finite differences for obtaining aerodynamic performance parameters.
Shaping the organizational learning strategy through customer journey mapping: insights from shopping mall operators
Authors: Lattuch Frank , Schlicht Christian , Dankert Patricia
Published: February 2023

Purpose

The purpose of this paper is to test a journey mapping approach as a first step to systematically prepare organizations for the many critical moments in B2B relationships.

Design/methodology/approach

By applying a case study of a shopping mall operator, experts on both sides of the B2B relationship (operator (n = 12) and retailer (n = 14)) were interviewed to develop and test the effectiveness of customer journey mapping. The information from these interviews was used to formulate several practical recommendations.

Findings

Using the journey mapping to differentiate, change from a touchpoint to a journey orientation, and shift towards cross-functional methods, all help develop a customer journey perspective and frame a culture that supports organizational development.

Originality/value

The discussion of the various benefits of journey mapping can improve organizational learning and provides practitioners with insights into effectively differentiating through a customer-centric orientation.
The role of stakeholders and their relationships in the sustainability of telecentres
Authors: Do Manh Thai , Dang Duong , Falch Morten , Tran Minh Tuan , Vu Phi Tuyen
Published: February 2023

Purpose

This paper aims to examine the role of stakeholders and their relationships in the sustainability of telecentres in Vietnam through the lens of stakeholder theory.

Design/methodology/approach

This study methodologically adopted a qualitative case study to identify stakeholders that have been involved in telecentres in Vietnam. It then categorizes those stakeholders’ salience through the lens of stakeholder identification and salience theory. Secondary data and interviews were used as data sources for the present paper.

Findings

The authors identify six main stakeholders that have been involved in telecentres, including the government, entrepreneurs, international donors, telecommunications providers, civil society organisations and individual community members/users. Among these stakeholders, the government, entrepreneurs and users belong to definitive stakeholders, which have the greatest impact on the sustainability of telecentres in comparison to other groups of stakeholders (e.g. dominant, dependent and dormant stakeholders). Moreover, the authors propose a model to identify the relationships of stakeholders towards the sustainability of telecentres. In particular, the authors indicate that each group of stakeholders has its own role in contributing to sustainable telecentres and they also influence others in either direct or indirect ways.

Originality/value

This study provides an additional approach for managers to make judgments in prioritizing the interests of some of their stakeholders while still maintaining a level of satisfaction among other stakeholders. For example, stakeholders that should be of the highest concern to the sustainability of telecentres are the government, entrepreneurs and users, while civil society organisations can be maintained in lower priority to other stakeholders. In addition, we propose the model of interactions and relationships of stakeholders, which can be seen as a starting point for a study on the roles of stakeholders in sustainability not only in telecentres, but also in other fields, such as digital transformation, cyber security and e-government.
Interaction and effects of dangerous and hidden points on firefighter’s health during fire overhaul using the PLS-SEM technique
Authors: Rahnama Neda , Noorzai Esmatullah , Golabchi Mahmood
Published: February 2023

Purpose

The existence of hidden and dangerous points after the fire leads to loss of command of the rescue teams, casualties, and financial loss. This paper aims to identify these points by taking into account their contributing factors that can help to better manage, prevent and prepare for the risks even after their occurrence.

Design/methodology/approach

In this study, the fire overhaul was investigated by identifying the risks of this stage and ranking them in terms of impact. This paper introduces danger points using empirical knowledge (questionnaire) along with theoretical knowledge (literature review) and suggested solutions. Finally, by investigating the dangers and their effects on each other, it introduced three main danger paths. The main problem is the lack of applied knowledge, the relationship between theoretical knowledge at this stage of fire and its application in firefighting operations. To solve this problem, a model was developed to determine the relationships between the effects on firefighters’ health during fire overhaul using structural equation modeling (SEM) in the building. To develop this model, dangerous points were first identified, categorized and weighted, and then the effect of each of these points and their interactions was determined.

Findings

This paper contributes to the literature by identifying hazardous points and investigating their impacts on firefighters’ health using the SEM method. This study identifies 17 points that can be traversed through three paths.

Research limitations/implications

Hazardous points could affect the success of the fire overhaul operation. Adopting a flexible model during this stage can enhance safety.

Originality/value

The results of this study can be used to rank and classify fire overhaul hazards in buildings and to increase firefighters’ safety and other related factors.
Mapping the scientific evolution of innovative work behavior: a bibliometric analysis of three decades
Authors: Peerzadah Sabzar Ahmad , Mufti Sabiya , Majeed Shayista
Published: February 2023

Purpose

This study aims to look at the current state of academic research on innovative work behavior (IWB) and how far it has progressed by using key performance analysis and science mapping techniques of bibliometric analysis.

Design/methodology/approach

This study has analyzed 246 publications from Web of Science database on IWB from 1989 to 2021. Data were analyzed using MS Excel and VOSviewer.

Findings

There has been a rise in the number of academic studies on IWB during the past decade. In addition, it was discovered that a significant percentage of papers had multiple authors working together on them and that collaborations between institutes in Asia and the developed world are taking place.

Research limitations/implications

IWB research trends and trajectories may be assessed to enable academics and practitioners better understand the current and future trends and research directions. Future studies in this field might use the findings as a starting point to highlight the nature of the topic.

Originality/value

Bibliometric techniques provide a far more comprehensive and reliable picture of the field. This article has the potential to serve as a one-stop resource for researchers and practitioners seeking information that can aid in transdisciplinary endeavors by leading them to recognized, peer-reviewed papers, journals and networks.
Metrics for measuring industrial sustainability performance in small and medium-sized enterprises
Authors: Mengistu Azemeraw Tadesse , Panizzolo Roberto
Published: February 2023

Purpose

This paper aims to identify and empirically analyze useful and applicable metrics for measuring and managing the sustainability performance of small and medium-sized enterprises (SMEs).

Design/methodology/approach

To achieve the objective of the paper, potential metrics were adopted from previous research related to industrial sustainability and an empirical analysis was carried to assess the applicability of the metrics by collecting empirical data from Italian footwear SMEs using a structured questionnaire. The SMEs were selected using a convenience sampling method.

Findings

The results of the within-case analysis and the cross-case analysis indicate that the majority of the metrics were found to be useful and applicable to each of the SMEs and across the SMEs, respectively. These metrics emphasized measuring industrial sustainability performance related to financial benefits, costs and market competitiveness for the economic sustainability dimension; resources for the environmental sustainability dimension; and customers, employees and the community for the social sustainability dimension.

Research limitations/implications

Apart from the within-case analysis and cross-case analysis, it was not possible to conduct statistical analysis since a small number of SMEs were accessible to collect empirical data.

Originality/value

The findings of the paper have considerable academic, managerial and policy implications and will provide a theoretical basis for future research on measuring and managing industrial sustainability performance. By providing a set of empirically supported metrics based on the triple bottom line approach (i.e. economic, environmental and social metrics), this paper contributes to the existing knowledge in the field of industrial sustainability performance measurement.
Investigating Japan’s physical education assistance to other countries: extraction of major categories and examination of their relevance
Authors: Shiraishi Tomoya
Published: February 2023

Purpose

This study aims to provide the history and overview of the major categories of physical education (PE) assistance that Japan has provided to other countries by extracting the major categories from the various materials.

Design/methodology/approach

This study is divided into two phases, Phases 1 and 2. Surveys and analyses were further conducted. In Phase 1, a web browser-based survey was conducted to ascertain the major categories of PE assistance that Japan has provided to other countries. The practices and projects investigated were classified inductively, and the major categories were extracted. In Phase 2, a literature review was conducted to organise the history and overview of each category extracted in Phase 1.

Findings

Six major categories were extracted: (1) dispatch of Japan Overseas Cooperation Volunteers engaged in PE assistance, (2) assistance through training for those involved in PE, (3) revision or formulation of a PE curriculum, (4) preparation of textbooks or instructional materials for PE, (5) organising sports event and (6) maintenance of PE equipment and facilities.

Originality/value

Japan has a long history of providing PE assistance to other countries. However, historical materials on the practices and projects of PE are becoming scattered. Little literature addresses this gap, which this study seeks to address. This study can help policy makers in other countries, who can use Japan’s PE assistance practices and policies for reference, to assist them in formulating their own policies.