bluuebunny/crossref_metadata_2025 huggingface dataset:
Expansion of a neural crest gene signature following ectopic MYCN expression in sympathoadrenal lineage cells in vivo
Authors: Ibarra-García-Padilla Rodrigo , Nambiar Annika , Hamre Thomas A. , Singleton Eileen W. , Uribe Rosa A.
Published: April 2024

Neural crest cells (NCC) are multipotent migratory stem cells which originate from the neural tube during early vertebrate embryogenesis. NCC give rise to a variety of cell types within the developing organism, including neurons and glia of the sympathetic nervous system. It has been suggested that failure in correct NCC differentiation leads to several diseases, including neuroblastoma (NB). During normal NCC development, MYCN is transiently expressed to promote NCC migration, and its downregulation precedes neuronal differentiation. Overexpression of MYCN has been linked to high-risk and aggressive NB progression. For this reason, understanding the effect overexpression of this oncogene has on development of NCC-derived sympathoadrenal progenitors (SAP), which later give rise to sympathetic nerves, will help elucidate the developmental mechanisms that may prime the onset of NB. Here, we found that overexpressing human EGFP-MYCN within SAP lineage cells in zebrafish led to the transient formation of an abnormal SAP population which displayed expanded and elevated expression of NCC markers, while paradoxically also co-expressing SAP and neuronal differentiation markers. The aberrant NCC signature was corroborated within vivotime lapse confocal imaging in zebrafish larvae, which revealed transient expansion ofsox10reporter expression in MYCN overexpressing SAPs during the early stages of SAP development. In these aberrant MYCN overexpressing SAP cells, we also found evidence of dampened BMP signaling activity, indicating that BMP signaling disruption occurs following elevated MYCN expression, and suggesting BMP is functionally important for the NCC to SAP differentiation transition. In agreement, we discovered that pharmacological inhibition of BMP signaling was sufficient to create an aberrant NCC gene signature in SAP cells, phenocopying MYCN overexpression. Together, our results suggest that MYCN overexpression in SAPs disrupts their differentiation by eliciting abnormal NCC gene expression programs, and dampening BMP signaling response, having developmental implications for the priming of NBin vivo.
Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections
Authors: Arévalo-Jaimes Betsy Veronica , Salinas-Pena Mónica , Ponte Inmaculada , Jordan Albert , Roque Alicia , Torrents Eduard
Published: April 2024

Histones possess significant antimicrobial potential, yet their activity against biofilms remains underexplored. Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombinant histone H1 subtypes againstPseudomonas aeruginosaPAO1, both planktonic and in biofilms. After thein vitrotests, toxicity and efficacy were assessed in aP. aeruginosaPAO1 infection model usingGalleria mellonellalarvae. Histones were also evaluated in combination with ciprofloxacin and gentamicin. Our results demonstrate antimicrobial activity against of all three histones againstP. aeruginosaPAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption.In vitrostudies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity inG. mellonellalarvae, and both increased larvae survival when infected withP. aeruginosaPAO1. Althoughin vitrosynergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was notedin vivo. Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such asP. aeruginosa.

Importance

The constant increase of multidrug-resistant bacteria is a critical global concern. The inefficacy of current therapies to treat bacterial infections is attributed to multiple mechanisms of resistance, including the capacity to form biofilms. Therefore, the identification of novel and safe therapeutic strategies is imperative. This study confirms the antimicrobial potential of three histone H1 subtypes against both Gram-negative and Gram-positive bacteria. Furthermore, histones H1.0 and H1.4 demonstratedin vivoefficacy without associated toxicity in an acute infection model ofPseudomonas aeruginosaPAO1 inGalleria mellonellalarvae. The bactericidal effect of these proteins also resulted in reduction in biomass ofP. aeruginosaPAO1 biofilms. Given the clinical significance of this opportunistic pathogen, our research provides a comprehensive initial evaluation of the efficacy, toxicity, and mechanism of action of a potential new therapeutic approach against acute and chronic bacterial infections.
CINner: modeling and simulation of chromosomal instability in cancer at single-cell resolution
Authors: Dinh Khanh N. , Vázquez-García Ignacio , Chan Andrew , Malhotra Rhea , Weiner Adam , McPherson Andrew W. , Tavaré Simon
Published: April 2024

Cancer development is characterized by chromosomal instability, manifesting in frequent occurrences of different genomic alteration mechanisms ranging in extent and impact. Mathematical modeling can help evaluate the role of each mutational process during tumor progression, however existing frameworks can only capture certain aspects of chromosomal instability (CIN). We present CINner, a mathematical framework for modeling genomic diversity and selection during tumor evolution. The main advantage of CINner is its flexibility to incorporate many genomic events that directly impact cellular fitness, from driver gene mutations to copy number alterations (CNAs), including focal amplifications and deletions, missegregations and whole-genome duplication (WGD). We apply CINner to find chromosome-arm selection parameters that drive tumorigenesis in the absence of WGD in chromosomally stable cancer types. We found that the selection parameters predict WGD prevalence among different chromosomally unstable tumors, hinting that the selective advantage of WGD cells hinges on their tolerance for aneuploidy and escape from nullisomy. Direct application of CINner to model the WGD proportion and fraction of genome altered (FGA) further uncovers the increase in CNA probabilities associated with WGD in each cancer type. CINner can also be utilized to study chromosomally stable cancer types, by applying a selection model based on driver gene mutations and focal amplifications or deletions. Finally, we used CINner to analyze the impact of CNA probabilities, chromosome selection parameters, tumor growth dynamics and population size on cancer fitness and heterogeneity. We expect that CINner will provide a powerful modeling tool for the oncology community to quantify the impact of newly uncovered genomic alteration mechanisms on shaping tumor progression and adaptation.
Telomere-to-telomere genome assembly of the clubroot pathogenPlasmodiophora brassicae
Authors: Javed Muhammad Asim , Mukhopadhyay Soham , Normandeau Eric , Brochu Anne-Sophie , Pérez-López Edel
Published: April 2024

Plasmodiophora brassicae (Woronin, 1877), a biotrophic, obligate parasite, is the causal agent of clubroot disease in brassicas. The clubroot pathogen has been reported in more than 80 countries worldwide, causing economic losses of hundreds of millions every year. Despite its widespread impact, very little is known about the molecular strategies it employs to induce the characteristic clubs in the roots of susceptible hosts during infection, nor about the mechanisms it uses to overcome genetic resistance. Here, we provide the first telomere-to-telomere complete genome of Plasmodiophora brassicae. We generated ∼ 27 Gb of Illumina, Oxford Nanopore, and PacBio HiFi data from resting spores of strain Pb3A and produced a 25.3 Mb assembly comprising 20 chromosomes, with an N50 of 1.37 Mb. The BUSCO score, the highest reported for any member of the group Rhizaria (Eukaryota: 88.2%), highlights the limitations within the Eukaryota database for members of this lineage. Using available transcriptomic data and protein evidence, we annotated the Pb3A genome, identifying 10,521 protein-coding gene models. This high-quality, complete genome of Plasmodiophora brassicae will serve as a crucial resource for the plant pathology community to advance the much-needed understanding of the evolution of the clubroot pathogen.

SIGNIFICANCE

Plasmodiophora brassicae (Woronin, 1877) is a devastating plant pathogen, member of the Rhizaria group, and is putting at risk the oilseed rape and cruciferous vegetable industry worldwide. Here, we present the first telomere-to-telomere genome of P. brassicae, and the first complete genome for a member of the Rhizaria taxon. We also provide a high-quality genome annotation featuring an enhanced gene model relative to previous studies. This complete genome will be of great interest to researchers focused on the ecology and evolution of the clubroot pathogen, as well as those studying other members of the Rhizaria group.
Exploring critical success factors for digital transformation in construction industry–based on TOE framework
Authors: Zhong Yi , Chen Zhiqian , Ye Jinglei , Zhang Na
Published: April 2024

Purpose

This study aims to investigate the critical success factors of digital transformation in the construction industry and identify whether the respondents' profiles influence their perceptions of critical success factors for digital transformation.

Design/methodology/approach

To achieve the objectives, a literature review was first conducted based on technology-organization-environment (TOE) framework. Then a questionnaire survey was carried out. A total of 86 people were surveyed in this study, mainly from the construction industry. At the level of data processing, SPSS was used for analysis. Among the main tests used were the Shapiro–Wilk test, reliability analysis, mean rank analysis, Kruskal–Wallis test and Mann–Whitney U test.

Findings

The study identified 15 critical success factors of digital transformation and found the three most important factors of digital transformation. Furthermore, respondents with different years of experience, enterprises with different sizes and different years made no difference in the perception of factors. Respondents' different occupations and types of enterprises created a bias in the perception of factors for digital transformation.

Research limitations/implications

Firstly, the small sample size of the questionnaire limits the reference value of data analysis for certain groups. In addition, this study focuses broadly on construction enterprises without specifically examining different types of enterprises, thus lacking depth in its findings.

Practical implications

This study establishes a connection between TOE theory and the construction industry through an extensive literature review, identifying relevant factors and providing a reference for future research.

Originality/value

The study's results would enrich the research on digital transformation in the construction industry and provide a reference for the digital transformation of construction enterprises.
Strengthening resilience in supply chains: the role of multi-layer flexibility, supply chain risks and environmental dynamism
Authors: Singh Rohit Kumar
Published: April 2024

Purpose

This study examines the relationship between multi-layer supply chain flexibility (MSCF) and Supply chain resilience (SCR). Further, it looks at the moderating effect of environmental dynamism (ED) and supply chain risks (SCRI) on the relationship between MSCF and SCR.

Design/methodology/approach

Executives from the pharmaceutical, agri-food, electronics, automobile and textile industries were invited to complete a self-administered questionnaire. We received feedback from a total of 302 participants. Prior to conducting the primary analysis, we addressed the potential for nonresponse bias and verified the assumptions of homoscedasticity and normal distribution of the data. The reliability and validity of the constructs were established through confirmatory factor analysis. Structural equation modelling is employed for the purpose of conducting hypothesis testing.

Findings

The results demonstrate a notable influence of MSCF on SCR, particularly in settings characterized by high levels of ED and SCRI. The study highlights the importance of flexibility in multiple aspects of the supply chain to build resilience against a range of disruptions and uncertainties.

Originality/value

The study presents the fundamental role of Multi-Layer Flexibility in building up SCR. The results of this study reinforce the existing literature and offers empirical evidence for how ED, SCRI moderates the influence between MSCF to SCR. These results offer valuable information to both supply chain specialists and researchers for building comprehensive strategy to bring resilience in supply chains.
Duality in barriers and enablers of augmented reality adoption in education: a systematic review of reviews
Authors: Albishri Baraa , Blackmore Karen L.
Published: April 2024

Purpose

The study aims to identify the key advantages/enablers and disadvantages/barriers of augmented reality (AR) implementation in education through existing reviews. It also examines whether these factors differ across educational domains.

Design/methodology/approach

This study conducted a systematic review of reviews to synthesize evidence on the barriers and enablers influencing AR adoption in education. Searches were performed across five databases, with 27 reviews meeting the inclusion criteria. Data extraction and quality assessment were completed. Content analysis was conducted using the AR adoption factor model and consolidated framework for implementation research.

Findings

The findings reveal several enablers such as pedagogical benefits, skill development and engagement. Equally, multiple barriers were identified, including high costs, technical issues, curriculum design challenges and negative attitudes. Interestingly, duality emerged, whereby some factors served as both barriers and enablers depending on the educational context.

Originality/value

This review contributes a novel synthesis of the complex individual, organizational and technological factors influencing AR adoption in education across diverse domains. The identification of duality factors provides nuanced understanding of the multifaceted dynamics shaping AR integration over time. The findings can assist educators in tailoring context-sensitive AR implementation strategies to maximize benefits and minimize drawbacks. Further research should explore duality factors and their interrelationships in AR adoption.
A comparative study of Indian and Chinese textile and clothing exports in post-MFA environment
Authors: Meena Anita
Published: April 2024

Purpose

This paper aims to examine and compare the export performance and competitiveness of Indian and Chinese textile and clothing industries post-multifibre arrangement (MFA) era.

Design/methodology/approach

Balassa’s revealed comparative advantage Index is used to assess the competitiveness of Indian and Chinese textile and clothing exports.

Findings

The results indicate that China’s textiles and garments sector holds a greater proportion of the global market compared with India. India has a robust comparative advantage in silk, carpets, and cotton post-MFA. Vegetable textile fibers, paper yarn, and woven fabrics of paper yarn are also competitive. China had a strong comparative advantage in silk and fabrics; special woven fabrics, tufted textile fabrics, lace, tapestries, trimmings, and embroidery in 2005. China also recorded comparative advantage in silk, man-made filaments: strip and the like of man-made textile materials, fabrics; special woven fabrics, tufted textile fabrics, lace, tapestries, trimmings, and embroidery and fabrics; knitted or crocheted in 2021.

Research limitations/implications

This study’s results and recommendations could assist the Indian and Chinese Governments develop policies to upgrade their garment industries.

Originality/value

Though vast literature reviews are available for textile and apparel export performance in India and China separately, there are few studies on comparisons. This study is a significant attempt to evaluate India and China’s competitiveness in the global market.
Potential use of yeast protein in terms of biorefinery, functionality, and sustainability in food industry
Authors: Timira Vaileth , Chen Xing , Zhou Peng , Wu Junjun , Wang Tao
Published: April 2024

A growing demand for sustainable, alternative protein sources that are nutrient‐dense, such as microorganisms, and insects, has gradually evolved. When paired with effective processing techniques, yeast cells contain substantial substances that could supply the population's needs for food, medicine, and fuel. This review article explores the potential of yeast proteins as a sustainable and viable alternative to animal and plant‐based protein sources. It highlights the various yeast protein extraction methods including both mechanical and non‐mechanical methods. The application of nanoparticles is one example of the fast‐evolving technology used to damage microbial cells. SiO2 or Al2O3 nanoparticles break yeast cell walls and disrupt membranes, releasing intracellular bioactive compounds. Succinylation of yeast protein during extraction can increase yeast protein extraction rate, lower RNA concentration, raise yeast protein solubility, increase amino acid content, and improve yeast protein emulsification and foaming capabilities. Combining physical and enzymatic extraction methods generates the most representative pool of mannose proteins from yeast cell walls. Ethanol or isoelectric precipitation purifies mannose proteins. Mannoproteins can be used as foamy replacement for animal‐derived components like egg whites due to their emulsification, stability, and foaming capabilities. Yeast bioactive peptide was separated by ultrafiltration after enzymatic hydrolysis of yeast protein and has shown hypoglycemic, hypotensive, and oxidative action in vitro studies. Additionally, the review delves into the physicochemical properties and stability of yeast‐derived peptides as well as their applications in the food industry. The article infers that yeast proteins are among the promising sources of sustainable protein, with a wide range of potential applications in the food industry.
Radical Urban Classrooms: Civic Pedagogies and Spaces of Learning on the Margins of Institutions
Authors: Antaki Nicola , Belfield Andrew , Moore Thomas
Published: April 2024

This paper investigates the relationship between “civic pedagogy” and institutions, through three case studies: the Live Works Castlegate Co‐Production at the University of Sheffield; a Collective Design Pedagogy at Muktangan School, India; and the School for Civic Action at the Tate Exchange. The projects aim to build citizens’ agency with transformative urban potential by engaging civic pedagogy using different scales, perspectives, and resources: as engagement with schools, higher education institutions, and art practices. Using Pelin Tan's definition of urgent pedagogies as a framework, this paper investigates the alternative alliances, trans‐territorial solidarities, and transversal methodologies of each project, comparing and contrasting methods and techniques. We discuss the potential for a shared decentralisation of learning associated with institutions, by engaging with the urban environment and communities, and propose a series of codependent practices for the initiation and sustenance of civic pedagogy for geographers interested in urban learning and education.
Allergic reaction of poly‐ether‐ether‐ketone versus titanium implants: A posttest‐only control group design experimental study using a rabbit model
Authors: Hassan Tamer Hamed , Ayappali Kalluvalappil Nabeel
Published: April 2024

Purpose

The aim of this study was to determine clinically and genetically the allergic effects of titanium and poly‐ether‐ether‐ketone (PEEK) implants following loading in rabbit tibias.

Materials and methods

This study included 18 white New Zealand male rabbits (n = 18) divided evenly into three groups: control, titanium (Ti), and PEEK (P). Clinically, the allergenic effect of titanium and PEEK was investigated by detecting the effect on lymph nodes. Furthermore, RT‐PCR and ELISA were used to detect the expression of certain genes IL‐6, TNF‐α, OPG, RANKL, and RUNX‐2 through both types of implants.

Results

Our findings demonstrated that titanium implants induced enlarged lymph nodes, which PEEK did not. Overall, RT‐PCR and ELISA techniques revealed that Ti implants had higher expression of the inflammatory genes IL‐6 and TNF‐α. Ti had the highest expression in OPG findings, while PEEK had the lowest. RANKL expression was highest in the control group and lowest in the PEEK group. RUNX‐2 is the highest for the control group and the lowest for the titanium group.

Conclusion

Although titanium implants elicited greater allergy responses than PEEK implants, titanium has the highest expression of bone formation genes and the lowest expression of bone resorption genes, making it preferable to PEEK.
Stigmasterol alleviates neuropathic pain by reducing Schwann cell‐macrophage cascade in DRG by modulating IL‐34/CSF1R
Authors: Si Waimei , Chen Zhenni , Bei Jing , Chang Shiquan , Zheng Yachun , Gao Li , Zhao Guoping , Li Xin , Zhang Di
Published: April 2024

Aims

This study aimed to investigate the potential therapeutic applications of stigmasterol for treating neuropathic pain.

Methods

Related mechanisms were investigated by DRG single‐cell sequencing analysis and the use of specific inhibitors in cellular experiments. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, CCI group, ibuprofen group, and stigmasterol group. We performed behavioral tests, ELISA, H&E staining and immunohistochemistry, and western blotting.

Results

Cell communication analysis by single‐cell sequencing reveals that after peripheral nerve injury, Schwann cells secrete IL‐34 to act on CSF1R in macrophages. After peripheral nerve injury, the mRNA expression levels of CSF1R pathway and NLRP3 inflammasome in macrophages were increased in DRG. In vitro studies demonstrated that stigmasterol can reduce the secretion of IL‐34 in LPS‐induced RSC96 Schwann cells; stigmasterol treatment of LPS‐induced Schwann cell‐conditioned medium (L‐S‐CM) does not induce the proliferation and migration of RAW264.7 macrophages; L‐S‐CM reduces CSF1R signaling pathway (CSF1R, P38MAPK, and NFκB) activation, NLRP3 inflammasome activation, and ROS production. In vivo experiments have verified that stigmasterol can reduce thermal and cold hyperalgesia in rat chronic compressive nerve injury (CCI) model; stigmasterol can reduce IL‐1β, IL‐6, TNF‐α, CCL2, SP, and PGE2 in serum of CCI rats; immunohistochemistry and western blot confirmed that stigmasterol can reduce the levels of IL‐34/CSF1R signaling pathway and NLRP3 inflammasome in DRG of CCI rats.

Conclusion

Stigmasterol alleviates neuropathic pain by reducing Schwann cell‐macrophage cascade in DRG by modulating IL‐34/CSF1R axis.
Molecular mechanism analyses of post‐traumatic epilepsy and hereditary epilepsy based on 10× single‐cell transcriptome sequencing technology
Authors: Wen Fang , Tan Zhigang , Huang Dezhi , Xiang Jun
Published: April 2024

Background

Single‐cell RNA sequencing analysis has been usually conducted on post‐traumatic epilepsy (PET) and hereditary epilepsy (HE) patients; however, the transcriptome of patients with traumatic temporal lobe epilepsy has rarely been studied.

Materials and Methods

Hippocampus tissues isolated from one patient with PTE and one patient with HE were used in the present study. Single cell isolates were prepared and captured using a 10× Genomics Chromium Single‐Cell 3′ kit (V3) according to the manufacturer's instructions. The libraries were sequenced on an Illumina NovaSeq 6000 sequencing system. Raw data were processed, and the cells were filtered and classified using the Seurat R package. Uniform Manifold Approximation and Projection was used for visualization. Differentially expressed genes (DEGs) were identified based on a p‐value ≤0.01 and log fold change (FC) ≥0.25. Gene Ontology (GO, http://geneontology.org/) and KEGG (Kyoto Encyclopedia of Genes and Genomes, www.genome.jp/kegg) analyses were performed on the DEGs for enrichment analysis.

Results

The reads obtained from the 10× genomic platform for PTE and HE were 39.56 M and 30.08 M, respectively. The Q30 score of the RNA reads was >91.6%. After filtering, 7479 PTE cells and 9357 HE cells remained for further study. More than 96.4% of the reads were mapped to GRCh38/GRCm38. The cells were differentially distributed in two groups, with higher numbers of oligodendrocytes (6522 vs. 2532) and astrocytes (133 vs. 52), and lower numbers of microglial cells (2242 vs. 3811), and neurons (3 vs. 203) present in the HE group than in the PTE group. The DEGs in four cell clusters were identified, with 25 being in oligodendrocytes (13 upregulated and 12 downregulated), 87 in microglia cells (42 upregulated and 45 downregulated), 222 in astrocytes (115 upregulated and 107 downregulated), and 393 in neurons (305 upregulated and 88 downregulated). The genes MTND1P23 (downregulated), XIST (downregulated), and RPS4Y1 (upregulated) were commonly expressed in all four cell clusters. The DEGs in microglial cells and astrocytes were enriched in the IL‐17 signaling pathway.

Conclusion

Our study explored differences in cells found in a patient with PE compared to a patient with HE, and the transcriptome in the different cells was analyzed for the first time. Studying inflammatory and immune functions might be the best approach for investigating traumatic temporal lobe epilepsy in neurons.
Okkludierende kutane Vaskulopathien als Ursachen chronischer Unterschenkelulzerationen
Authors: Ronicke Moritz , Berking Carola , Erfurt‐Berge Cornelia
Published: April 2024

Unter den Begriff der okkludierenden Vaskulopathien fällt eine Reihe unterschiedlicher Krankheitsbilder. Diese manifestieren sich an der Haut häufig mit Ulzerationen. Gerade bei Ulzerationen der Unterschenkel sollten okkludierende Vaskulopathien in die differenzialdiagnostischen Überlegungen einbezogen werden. Der Begriff „okkludierende Vaskulopathien“ umfasst pathophysiologisch verwandte Entitäten, die eine strukturelle oder thrombotische Obliteration von kleinsten Hautgefäßen gemein haben. In diesem Artikel wird vor allem auf die Livedovaskulopathie mit und ohne Antiphospholipidsyndrom sowie die Calciphylaxie mit Abgrenzung zum Ulcus cruris hypertonicum als die relevantesten Differenzialdiagnosen von Unterschenkelulzerationen eingegangen. Der Begriff umfasst auch Gefäßverschlüsse, beispielsweise durch Oxalat oder Cholesterinembolie, sowie die septische Vaskulopathie. Diese führt häufig zu akralen Ulzerationen und stellt somit keine Differenzialdiagnose zum klassischen Ulcus cruris dar. Sie wird daher in diesem Artikel nicht behandelt.

Der Verdacht einer okkludierenden Vaskulopathie kann über die typische Livedo racemosa beziehungsweise die (nichtinflammatorische) retiforme Purpura als Zeichen der kutanen Minderdurchblutung in der Wundumgebung gestellt werden. Entzündliche Dermatosen, insbesondere Vaskulitiden, müssen differenzialdiagnostisch abgegrenzt werden. Dies geschieht zum Teil klinisch und durch die histopathologische Beurteilung einer Gewebeprobe, die in ausreichender Größe und Tiefe sowie zum richtigen Zeitpunkt entnommen werden muss. Ergänzend können spezifische Laborparameter, insbesondere die Gerinnungsdiagnostik, die Diagnosestellung unterstützen.
S2k‐Leitlinie: Diagnostik und Therapie der zirkumskripten Sklerodermie
Authors: Kreuter Alexander , Moinzadeh Pia , Kinberger Maria , Horneff Gerd , Worm Margitta , Werner Ricardo N. , Hammacher Andreas , Krieg Thomas , Wenzel Jörg , Oeschger Michael , Weibel Lisa , Müllegger Robert , Hunzelmann Nicolas
Published: April 2024

Die vorliegende aktualisierte S2k‐Leitlinie befasst sich mit der Diagnostik und der Therapie der zirkumskripten Sklerodermie (ZS). Diese umfasst ein Spektrum sklerotischer Erkrankungen der Haut mit, je nach Subtyp und Lokalisation, möglicher Beteiligung von hautnahen Strukturen wie Fettgewebe, Muskulatur, Gelenke und Knochen. Ein Befall innerer Organe oder ein Übergang in eine systemische Sklerodermie treten nicht auf. Eingeteilt werden kann die ZS in die vier Hauptformen der limitierten, generalisierten, linearen und gemischten Form. Teilweise existieren weitere Unterformen. Bei limitiertem Hautbefall empfiehlt die Leitlinie primär eine Therapie mit topischen Kortikosteroiden. Eine UV‐Therapie kann ebenfalls sinnvoll sein. Bei Subtypen mit schwerem Hautbefall oder muskuloskelettalem Befall wird eine systemische Therapie mit Methotrexat empfohlen. In der aktiven Phase der Erkrankung können ergänzend systemische Glukokortikosteroide eingesetzt werden. Bei MTX‐ und Steroid‐refraktären Verläufen, Kontraindikation oder Unverträglichkeit sollten Mycophenolat‐Mofetil, Mycophenolsäure oder Abatacept als Systemtherapie der zweiten Wahl eingesetzt werden. Bei einer linearen ZS kann zudem eine autologe Fettstammzelltransplantation zur Korrektur von Weichteildefekten erfolgen.
A critical role of Ca2+/calmodulin‐dependent protein kinase II in coupling between evening and morning circadian oscillators in the suprachiasmatic nucleus
Authors: Yoshikawa Tomoko , Honma Ken‐ichi , Shigeyoshi Yasufumi , Yamagata Yoko , Honma Sato
Published: April 2024

Ca2+/calmodulin‐dependent protein kinase IIα (CaMKIIα) is widely expressed in the brain and is involved in various functions, including memory formation, mood and sleep. We previously reported that CaMKIIα is involved in the circadian molecular clock. Mice lacking functional CaMKIIα (K42R mice) exhibited a gradual increase in activity time (α decompression) of running‐wheel (RW) activity due to a lengthened circadian period (τ) of activity offset under constant darkness (DD). In the present study, to investigate the functional roles of CaMKIIα in behavioural rhythms, we measured RW and general movements simultaneously under prolonged DD. Tau became longer as the relative intensity of behaviour activity within an activity time shifted from activity onset towards activity offset. In some K42R mice, α was gradually expanded with a marked reduction of RW activity, while general movements persisted without noticeable decline, which was followed by an abrupt shortening of α (α compression) with differential phase shifts of the activity onset and offset and recovery of RW activity. These results suggest that an internal coupling between the oscillators controlling activity onset and offset is bidirectional but with different strengths. The α compression occurred recurrently in 38% of K42R mice examined with an average interval of 37 days in association with attenuation of RW activity but never in the wild‐type (WT) mice. Consistent with behavioural rhythms, the circadian period of the PER2::LUC rhythm in the cultured suprachiasmatic nucleus (SCN) slice was significantly longer in K42R than in WT. These findings are best interpreted by assuming that a loss of functional CaMKIIα attenuates the coupling between the onset and offset oscillators.
Deciphering cutaneous melanoma prognosis through LDL metabolism: Single‐cell transcriptomics analysis via 101 machine learning algorithms
Authors: Xie Jiaheng , Wu Dan , Zhang Pengpeng , Zhao Songyun , Qi Min
Published: April 2024

Cutaneous melanoma poses a formidable challenge within the field of oncology, marked by its aggressive nature and capacity for metastasis. Despite extensive research uncovering numerous genetic and molecular contributors to cutaneous melanoma development, there remains a critical knowledge gap concerning the role of lipids, notably low‐density lipoprotein (LDL), in this lethal skin cancer. This article endeavours to bridge this knowledge gap by delving into the intricate interplay between LDL metabolism and cutaneous melanoma, shedding light on how lipids influence tumour progression, immune responses and potential therapeutic avenues. Genes associated with LDL metabolism were extracted from the GSEA database. We acquired and analysed single‐cell sequencing data (GSE215120) and bulk‐RNA sequencing data, including the TCGA data set, GSE19234, GSE22153 and GSE65904. Our analysis unveiled the heterogeneity of LDL across various cell types at the single‐cell sequencing level. Additionally, we constructed an LDL‐related signature (LRS) using machine learning algorithms, incorporating differentially expressed genes and highly correlated genes. The LRS serves as a valuable tool for assessing the prognosis, immunity and mutation status of patients with cutaneous melanoma. Furthermore, we conducted experiments on A375 and WM‐115 cells to validate the function of PPP2R1A, a pivotal gene within the LRS. Our comprehensive approach, combining advanced bioinformatics analyses with an extensive review of current literature, presents compelling evidence regarding the significance of LDL within the cutaneous melanoma microenvironment.
Increasing spread rates of tropical non‐native macrophytes in the Mediterranean Sea
Authors: Wesselmann Marlene , Hendriks Iris E. , Johnson Mark , Jordà Gabriel , Mineur Frederic , Marbà Núria
Published: April 2024

Warming as well as species introductions have increased over the past centuries, however a link between cause and effect of these two phenomena is still unclear. Here we use distribution records (1813–2023) to reconstruct the invasion histories of marine non‐native macrophytes, macroalgae and seagrasses, in the Mediterranean Sea. We defined expansion as the maximum linear rate of spread (km year−1) and the accumulation of occupied grid cells (50 km2) over time and analyzed the relation between expansion rates and the species' thermal conditions at its native distribution range. Our database revealed a marked increase in the introductions and spread rates of non‐native macrophytes in the Mediterranean Sea since the 1960s, notably intensifying after the 1990s. During the beginning of this century species velocity of invasion has increased to 26 ± 9 km2 year−1, with an acceleration in the velocity of invasion of tropical/subtropical species, exceeding those of temperate and cosmopolitan macrophytes. The highest spread rates since then were observed in macrophytes coming from native regions with minimum SSTs two to three degrees warmer than in the Mediterranean Sea. In addition, most non‐native macrophytes in the Mediterranean (>80%) do not exceed the maximum temperature of their range of origin, whereas approximately half of the species are exposed to lower minimum SST in the Mediterranean than in their native range. This indicates that tropical/subtropical macrophytes might be able to expand as they are not limited by the colder Mediterranean SST due to the plasticity of their lower thermal limit. These results suggest that future warming will increase the thermal habitat available for thermophilic species in the Mediterranean Sea and continue to favor their expansion.
Projected ocean temperatures impair key proteins used in vision of octopus hatchlings
Authors: Hua Qiaz Q. H. , Kültz Dietmar , Wiltshire Kathryn , Doubleday Zoe A. , Gillanders Bronwyn M.
Published: April 2024

Global warming is one of the most significant and widespread effects of climate change. While early life stages are particularly vulnerable to increasing temperatures, little is known about the molecular processes that underpin their capacity to adapt to temperature change during early development. Using a quantitative proteomics approach, we investigated the effects of thermal stress on octopus embryos. We exposed Octopus berrima embryos to different temperature treatments (control 19°C, current summer temperature 22°C, or future projected summer temperature 25°C) until hatching. By comparing their protein expression levels, we found that future projected temperatures significantly reduced levels of key eye proteins such as S‐crystallin and retinol dehydrogenase 12, suggesting the embryonic octopuses had impaired vision at elevated temperature. We also found that this was coupled with a cellular stress response that included a significant elevation of proteins involved in molecular chaperoning and redox regulation. Energy resources were also redirected away from non‐essential processes such as growth and digestion. These findings, taken together with the high embryonic mortality observed under the highest temperature, identify critical physiological functions of embryonic octopuses that may be impaired under future warming conditions. Our findings demonstrate the severity of the thermal impacts on the early life stages of octopuses as demonstrated by quantitative proteome changes that affect vision, protein chaperoning, redox regulation and energy metabolism as critical physiological functions that underlie the responses to thermal stress.
Interplay of management and environmental drivers shifts size structure of reef fish communities
Authors: Canty Steven W. J. , Nowakowski A. Justin , Cox Courtney E. , Valdivia Abel , Holstein Daniel M. , Limer Benjamin , Lefcheck Jonathan S. , Craig Nicole , Drysdale Ian , Giro Ana , Soto Mélina , McField Melanie
Published: April 2024

Countries are expanding marine protected area (MPA) networks to mitigate fisheries declines and support marine biodiversity. However, MPA impact evaluations typically assess total fish biomass. Here, we examine how fish biomass disaggregated by adult and juvenile life stages responds to environmental drivers, including sea surface temperature (SST) anomalies and human footprint, and multiple management types at 139 reef sites in the Mesoamerican Reef (MAR) region. We found that total fish biomass generally appears stable across the region from 2006 to 2018, with limited rebuilding of fish stocks in MPAs. However, the metric of total fish biomass masked changes in fish community structure, with lower adult than juvenile fish biomass at northern sites, and adult:juvenile ratios closer to 1:1 at southern sites. These shifts were associated with different responses of juvenile and adult fish to environmental drivers and management. Juvenile fish biomass increased at sites with high larval connectivity and coral cover, whereas adult fish biomass decreased at sites with greater human footprint and SST anomalies. Adult fish biomass decreased primarily in Honduran general use zones, which suggests insufficient protection for adult fish in the southern MAR. There was a north–south gradient in management and environmental drivers, with lower coverage of fully protected areas and higher SST anomalies and coastal development in the south that together may undermine the maintenance of adult fish biomass in the southern MAR. Accounting for the interplay between environmental drivers and management in the design of MPAs is critical for increasing fish biomass across life history stages.
Study on magnesia alumina spinel heat storage ceramics for solar thermal power generation
Authors: Xu Xiaohong , Cheng Tiantian , Hao Shuai , Wu Jianfeng , Zhou Yang , Qiu Saixi
Published: April 2024

Solar thermal storage ceramic materials use photothermal power generation technology to store heat energy, which is an important way to use clean energy and reduce carbon emissions. In this paper, MgAl2O4 ceramics were prepared by pressureless sintering with fused magnesia and α‐Al2O3 as the primary raw materials and TiO2 as the additive. The phase composition, microstructure, physical properties, thermal shock resistance, and thermal physical properties of MgAl2O4 thermal storage ceramics were studied. The results show that the main crystalline phase of B4 is MgAl2O4 and the secondary crystalline phase is MgTi2O5. Ti4+ is dissolved into MgAl2O4 lattice, which distorts the lattice, reduces activation energy, and promotes sintering. The sample B4 (69.73 wt% α‐Al2O3, 30.27 wt% fused magnesia, and 7 wt% TiO2) sintered at 1510°C had the best comprehensive physical properties, and its bending strength and bulk density were 89.41 MPa and 3.27 g/cm3, respectively. After 30 thermal shock cycles, the bending strength of the sample B4 is slightly lost. The thermal stress generated during the expansion and contraction of the grain volume led to the decrease of the bending strength. From room temperature to 1000°C, the specific heat capacity of sample B4 is .44–1.25 J/(g·K). The heat capacity increases with the increase of temperature, and the heat storage density increases. The heat storage density is 1218.75 kJ/kg (1000°C). Heat capacity increases with temperature due to intensified lattice vibration at high temperatures. Therefore, magnesia alumina spinel ceramics show great potential in solar thermal energy storage.
Evaluation of the clinical application of personalized 3D printing and CAD/CAM resin crowns to replace stainless steel crowns in paediatric dentistry
Authors: Huang Huei‐Yu , Yang Ya‐Ting , Chuang Chun‐Chao , Shen Yung‐Kang , Chen Mu‐Hsiung , Lin Wei‐Chun
Published: April 2024

Background

Children with dental caries are treated with stainless steel metal crowns (SSC), but the aesthetics and precision still need to be improved. Currently, both 3D‐printed resin crowns (PRC) and computer‐aided design/computer‐aided manufacture (CAD/CAM) resin crowns (CRC) meet the clinical requirements for crown applications in terms of strength, production time, cost, and aesthetics.

Aim

This study replaced SSC with customized resin crowns by 3D printing and CAD/CAM.

Design

In this study, PRC, CRC, and SSC were used for incisor and molar restorations, and 60 crowns were made with 10 for each group. The fabrication efficiency, surface characteristics, marginal fit, and stability of the two different crowns were evaluated.

Results

PRC and CRC show superior color and surface characteristics, though production times are longer (5.3–12.4 times and 3.3–9.1 times, respectively) than for SSC (p < .05). They, however, can be completed within 80 min. Edge gaps for PRC and CRC are significantly lower (13.0–19.2 times and 13.0–13.7 times) than for SSC (p < .05). All materials exhibit good stability.

Conclusion

The 3D‐PRCs and CAD/CAM resin crowns may replace SSCs as a potential choice for clinical child caries.
High‐Dose Quadrivalent Influenza Vaccine for Prevention of Cardiovascular and Respiratory Hospitalizations in Older Adults
Authors: Palmu Arto A. , Pepin Stephanie , Syrjänen Ritva K. , Mari Karine , Mallett Moore Tamala , Jokinen Jukka , Nieminen Heta , Kilpi Terhi , Samson Sandrine I. , De Bruijn Iris
Published: April 2024

Background

We assessed the relative vaccine effectiveness (rVE) of high‐dose quadrivalent influenza vaccine (QIV‐HD) versus standard‐dose quadrivalent influenza vaccine (QIV‐SD) in preventing respiratory or cardiovascular hospitalizations in older adults.

Methods

FinFluHD was a phase 3b/4 modified double‐blind, randomized pragmatic trial. Enrolment of 121,000 adults ≥65 years was planned over three influenza seasons (October to December 2019–2021). Participants received a single injection of QIV‐HD or QIV‐SD. The primary endpoint was first occurrence of an unscheduled acute respiratory or cardiovascular hospitalization (ICD‐10 primary discharge J/I codes), from ≥14 days post‐vaccination until May 31. The study was terminated after one season due to COVID‐19; follow‐up data for 2019–2020 are presented.

Results

33,093 participants were vaccinated (QIV‐HD, n = 16,549; QIV‐SD, n = 16,544); 529 respiratory or cardiovascular hospitalizations (QIV‐HD, n = 257; QIV‐SD, n = 272) were recorded. The rVE of QIV‐HD versus QIV‐SD to prevent respiratory/cardiovascular hospitalizations was 5.5% (95% CI, −12.4 to 20.7). When prevention of respiratory and cardiovascular hospitalizations were considered separately, rVE estimates of QIV‐HD versus QIV‐SD were 5.4% (95% CI, −28.0 to 30.1) and 7.1% (95% CI, −15.0 to 25.0), respectively. Serious adverse reactions were <0.01% in both groups.

Conclusions

Despite insufficient statistical power due to the impact of COVID‐19, rVE point estimates demonstrated a trend toward a benefit of QIV‐HD over QIV‐SD. QIV‐HD was associated with lower respiratory or cardiovascular hospitalization rates than QIV‐SD, with a comparable safety profile. Adequately powered studies conducted over multiple influenza seasons are needed to determine statistical significance of QIV‐HD compared with QIV‐SD against preventing respiratory and cardiovascular hospitalizations.

Trial Registration: ClinicalTrials.gov number: NCT04137887
Identification of IGF2 promotes skin wound healing by co‐expression analysis
Authors: Liu Xingyan , Teng Ying , Li Huan , Luo Ding , Li Hongkun , Shen Jinghan , Du Simin , Zhang Yuyue , Wang Dali , Jing Jie
Published: April 2024

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co‐expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re‐epithelialization and accelerated wound healing in a full‐thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.
Thermal shock resistance of a novel (Gd1/6Tb1/6Dy1/6Tm1/6Yb1/6Lu1/6)2Si2O7 environmental barrier coating
Authors: Yan Lingxuan , Peng Yin , Luo Zhixin , Wang Haoyu , Wang Ziyu , Luo Yixiu , Wang Jiemin , Sun Luchao , Wang Jingyang
Published: April 2024

Multicomponent rare earth (RE) disilicates have been recognized as promising candidates for environmental barrier coatings (EBCs). In this work, a novel EBC system with (Gd1/6Tb1/6Dy1/6Tm1/6Yb1/6Lu1/6)2Si2O7 as top coat and Si as bond coat was deposited on SiC‐based substrates by atmospheric plasma spraying technology and subjected to 200 thermal shock cycles at 1350°C. The composition and microstructure evolution in the coating during thermal cycling were investigated using x‐ray diffraction analysis and scanning electron microscopy. The results show that the as‐prepared EBC remains dense and integrated, and no obvious spalling or penetrating cracks could be observed in the coating after 200 thermal shock cycles. Furthermore, the average thickness of thermal growth oxide layer between (6RE1/6)2Si2O7 top coat and Si bond coat is 0.71 ± 0.17 µm and 0.98 ± 0.23 µm before and after the thermal cycling, respectively, indicating the excellent thermal shock resistance of (6RE1/6)2Si2O7 EBC. The present study presents a novel EBC with excellent thermal shock ability and is expected to contribute to the development of EBC for advanced SiCf/SiC ceramic matrix composites.