bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative study of skeletal muscle mitochondrial dysfunction in a murine pancreatic cancer-induced cachexia model
Authors: Gicquel Tristan , Marchiano Fabio , Reyes-Castellanos Gabriela , Audebert Stéphane , Camoin Luc , Habermann Bianca , Giannesini Benoit , Carrier Alice
Published: December 2022

Aims

Pancreatic Ductal AdenoCarcinoma (PDAC), the most common pancreatic cancer, is a deadly cancer, often diagnosed late and resistant to current therapies. PDAC patients are frequently affected by cachexia characterized by muscle mass and strength loss (sarcopenia) contributing to patient frailty and poor therapeutic response. The objective of this work was to investigate the mechanisms underlying mitochondrial remodeling in the cachectic skeletal muscle, through an integrative study combining functional, morphological and omics-based evaluation of gastrocnemius muscle from genetically-engineered mice developing autochthonous pancreatic tumor and cachexia (KIC GEMM).

Results

KIC cachectic PDAC mice exhibit severe sarcopenia with loss of muscle mass and strength associated with reduced muscle fiber’s size and induction of protein degradation processes. Mitochondria in PDAC atrophied muscles show reduced respiratory capacities and structural alterations, associated with deregulation of oxidative phosphorylation and mitochondrial dynamics pathways. Beyond the metabolic pathways known to be altered in sarcopenic muscle (carbohydrates, proteins, and redox), lipid and nucleic acid metabolisms are also affected. While the number of mitochondria per cell is not altered, mitochondrial mass is decreased by a factor of 2 and the mitochondrial DNA by a factor of 3, suggesting a defect in mitochondrial genome homeostasis.

Innovation

Muscle atrophy is associated with strong mitochondrial metabolic defects that are not limited to carbohydrate, protein and redox metabolism, but concern also lipid and nucleic acid metabolism.

Conclusion

This work provides a framework to guide towards the most relevant targets in the clinic to limit PDAC-induced cachexia, in particular mitochondrial fatty acid metabolism.
Interfacial dynamics and growth modes ofβ2-microglobulin dimers
Authors: Oliveira Nuno F. B. , Rodrigues Filipe E. P. , Vitorino João N. M. , Faísca Patrícia F. N. , Machuqueiro Miguel
Published: December 2022

Protein aggregation is a complex process that strongly depends on environmental conditions and has considerable structural heterogeneity, not only at the level of fibril structure but also at the level of molecular oligomerization. Since the first step in aggregation is the formation of a dimer, it is important to clarify how certain properties (e.g., stability or the interface geometry) of the latter may determine the outcome of aggregation. Here, we developed a simple model that represents the dimer’s interfacial region by two angles (spanning the so-called growth landscape), and investigate how modulations of the interfacial region occurring on the ns–μs timescale change the dimer’s growth mode. We applied this methodology to 15 different dimer configurations of theβ2m D76N mutant protein equilibrated with long MD simulations and identified which of them have limited and unlimited growth modes, with different consequences to their aggregation potential. We found that despite the highly dynamic nature of the starting configurations, most polymeric growth modes tend to be conserved within the studied time scale. The proposed methodology performs remarkably well taking into consideration that theβ2m dimers are formed by monomers with detached termini, and their interfaces are stabilized by non-specific apolar interactions, leading to relatively weak binding affinities.
Exact distribution of the quantal content in synaptic transmission
Authors: Rijal Krishna , Müller Nicolas I.C. , Friauf Eckhard , Singh Abhyudai , Prasad Ashok , Das Dibyendu
Published: December 2022

During electro-chemical signal transmission through synapses, triggered by an action potential (AP), a stochastic number of synaptic vesicles (SV), called thequantal content, release neurotransmitters in the synaptic cleft. It is widely accepted that the quantal content probability distribution is a binomial based on the number of ready-release SVs in the pre-synaptic terminal. But the latter number itself fluctuates due to its stochastic replenishment, hence the actual distribution of quantal content is unknown. We show that exact distribution of quantal content can be derived for general stochastic AP inputs in the steady-state. For fixed interval AP train, we prove that the distribution is a binomial, and corroborate our predictions by comparison with electrophysiological recordings from MNTB-LSO synapses of juvenile mice. For a Poisson train, we show that the distribution is non-binomial. Moreover, we find exact moments of the quantal content in the Poisson and other general cases, which may be used to obtain the model parameters from experiments.
Defining ancestry, heritability and plasticity of cellular phenotypes in somatic evolution
Authors: Schiffman Joshua S. , D’Avino Andrew R. , Prieto Tamara , Pang Yakun , Fan Yilin , Rajagopalan Srinivas , Potenski Catherine , Hara Toshiro , Suvà Mario L. , Gawad Charles , Landau Dan A.
Published: December 2022

The broad application of single-cell RNA sequencing has revealed transcriptional cell state heterogeneity across diverse healthy and malignant somatic tissues. Recent advances in lineage tracing technologies have further enabled the simultaneous capture of cell transcriptional state along with cellular ancestry thus enabling the study of somatic evolution at an unprecedented resolution; however, new analytical approaches are needed to fully harness these data. Here we introduce PATH (Phylogenetic Analysis of Transcriptional Heritability), an analytical framework, which draws upon classic approaches in species evolution, to quantify heritability and plasticity of somatic phenotypes, including transcriptional states. The PATH framework further allows for the inference of cell state transition dynamics by linking a model of cellular evolutionary dynamics with our measure of heritability versus plasticity. We evaluate the robustness of this approach by testing a range of biological and technical features in simulations of somatic evolution. We then apply PATH to characterize previously published and newly generated single-cell phylogenies, reconstructed from either native or artificial lineage markers, with matching cellular state profiling. PATH recovered developmental relationships in mouse embryogenesis, and revealed how anatomic proximity influences neural relatedness in the developing zebrafish brain. In cancer, PATH dissected the heritability of the epithelial-to-mesenchymal transition in a mouse model of pancreatic cancer, and the heritability versus plasticity of transcriptionally-defined cell states in human glioblastoma. Finally, PATH revealed phenotypic heritability patterns in a phylogeny reconstructed from single-cell whole genome sequencing of a B-cell acute lymphoblastic leukemia patient sample. Altogether, by bringing together perspectives from evolutionary biology and emerging single-cell technologies, PATH formally connects the analysis of cell state diversity and somatic evolution, providing quantification of critical aspects of these processes and replacingqualitativeconceptions of “plasticity” withquantitativemeasures of cell state transitions and heritability.
Neuron types in the developing mouse brain are divided into partially matching epigenomic and transcriptomic classes
Authors: Kilpinen Sami , Heliölä Heidi , Achim Kaia
Published: December 2022

In recent single-cell -omics studies, both the differential activity of transcription factors regulating cell fate determination and differential genome activation have been tested for utility as descriptors of cell types. Naturally, genome accessibility and gene expression are interlinked. To understand the variability in genomic feature activation in the GABAergic neurons of different spatial origins, we have mapped accessible chromatin regions and mRNA expression in single cells derived from the developing mouse central nervous system (CNS). We first defined a reference set of open chromatin regions for scATAC-seq read quantitation across samples, allowing comparison of chromatin accessibility between brain regions and cell types directly. Second, we integrated the scATAC-seq and scRNA-seq data to form a unified resource of transcriptome and chromatin accessibility landscape for the cell types in di- and telencephalon, midbrain and anterior hindbrain of E14.5 mouse embryo. Importantly, we implemented resolution optimization at the clustering, and automatized the cell typing step. We show high level of concordance between the cell clustering based on the chromatin accessibility and the transcriptome in analyzed neuronal lineages, indicating that both genome and transcriptome features can be used for cell type definition. Hierarchical clustering by the similarity in accessible chromatin reveals that the genomic feature activation correlates with neurotransmitter phenotype, selector gene expression, cell differentiation stage and neuromere origins.
Evolutionary divergence of basal and activity-dependent exon splicing in cortical neurons
Authors: Dando Owen , Qiu Jing , Chandran Siddharthan , Hardingham Giles E.
Published: December 2022

Alternative splicing of mRNA exons in mammalian neurons increases diversity of the proteome and is regulatable by signaling pathways. However, the degree of conservation of basal and signal-dependent exon usage between human neurons and those from experimental models such as mice is incompletely understood. We previously showed that cortical neuronal activity-dependent gene transcription exhibits human/mouse differences, driven by evolutionary divergence of cis-acting promoter elements (Qiu et al. 2016). Since alternative exon usage influences brain development and cognition, is controlled by neuronal activity, and is disturbed in brain disorders, we investigated human/mouse differences in exon usage in cortical neurons. Comparing orthologous exons, basal exon inclusion levels showed human-mouse conservation, but also significant differences determined by cis-acting sequences: human-mouse conservation and divergence in exon usage was recapitulated in neurons from Tc1 mice carrying human chromosome-21 (hCh21). Activity-dependent changes in exon usage also exhibited significant conservation: gene structure was more likely to be conserved in activity-regulated exons, and exons regulated in both human and mouse neurons were enriched in RBFOX and SAM68 targets, and genes were centred on cytoskeletal organisation, mRNA transcription/processing, and synaptic signaling. However, divergence was also evident, and human-specific activity-dependent exon usage was dominated by genes involved in lipid biosynthesis, signaling and trafficking. Notably, the pattern of activity-dependent usage of hCh21 exons in human neurons was not recapitulated in mouse Tc1 neurons. Thus, unlike species-specific differences in activity-dependent gene transcription, cis-acting DNA sequence divergence is insufficient to explain inter-species differences in activity-regulated exon usage. Trans-acting factors involved in activity-responsive splicing have likely also diverged.
FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1
Authors: Wang Dongyang , Zheng Xiaojing , Chai Lihong , Zhao Junli , Zhu Jiuling , Li Yanqing , Yang Peiyan , Mao Qinwen , Xia Haibin
Published: December 2022

FAM76B has been reported to be a nuclear speckle localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1in vitro.We further showed that FAM76B suppressed inflammation by regulating the NF-κB pathwayin vivousing a traumatic brain injury (TBI) model in FAM76B knockout mice. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediates neuroinflammation by influencing the translocation of hnRNPA2B1in vivoduring TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-κB-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.
A new type of transcriptional reprogramming by an IRF4 mutation in lymphoma
Authors: Schleussner Nikolai , Cauchy Pierre , Franke Vedran , Giefing Maciej , Fornes Oriol , Vankadari Naveen , Assi Salam , Costanza Mariantonia , Weniger Marc A. , Akalin Altuna , Anagnostopoulos Ioannis , Bukur Thomas , Casarotto Marco G. , Damm Frederik , Daumke Oliver , Edginton-White Benjamin , Gebhardt J. Christof M. , Grau Michael , Grunwald Stephan , Hansmann Martin-Leo , Hartmann Sylvia , Huber Lionel , Kärgel Eva , Lusatis Simone , Noerenberg Daniel , Obier Nadine , Pannicke Ulrich , Pfaus Anja , Reisser Anja , Rosenwald Andreas , Schwarz Klaus , Sundararaj Srinivasan , Weilemann Andre , Winkler Wiebke , Xu Wendan , Lenz Georg , Rajewsky Klaus , Wasserman Wyeth W. , Cockerill Peter N. , Scheidereit Claus , Siebert Reiner , Küppers Ralf , Grosschedl Rudolf , Janz Martin , Bonifer Constanze , Mathas Stephan
Published: December 2022

SUMMARY PARAGRAPH

Disease-causing mutations in genes encoding transcription factors (TFs) are a recurrent finding in hematopoietic malignancies and might involve key regulators of lineage adherence and cellular differentiation1–3. Such mutations can affect TF-interactions with their cognate DNA-binding motifs4, 5. Whether and how TF-mutations impact upon the nature of binding to TF composite elements (CE) and influence their interaction with other TFs is unclear. Here, we report a new mechanism of TF alteration in human lymphomas with perturbed B cell identity. It is caused by a recurrent somatic missense mutation c.295T>C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cell-differentiation and -activation6, 7. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF composite elements (CEs). Furthermore, IRF4-C99R thoroughly modifies IRF4 function, by blocking IRF4-dependent plasma cell induction, and up-regulating disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single arginine mutation creates a complex switch of TF specificity and gene regulation. These data open the possibility of designing specific inhibitors to block the neomorphic, disease-causing DNA-binding activities of a mutant transcription factor.
Repurposing of the antibiotic nitroxoline for the treatment of mpox
Authors: Bojkova Denisa , Zöller Nadja , Tietgen Manuela , Steinhorst Katja , Bechtel Marco , Rothenburger Tamara , Kandler Joshua D. , Schneider Julia , Corman Victor M. , Ciesek Sandra , Rabenau Holger F. , Wass Mark N. , Kippenberger Stefan , Göttig Stephan , Michaelis Martin , Cinatl Jindrich
Published: December 2022

The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side-effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat-resistant strain and increased the anti-mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co-transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity.
A broad matrix metalloproteinase inhibitor with designed loop extension exhibits ultrahigh specificity for MMP-14
Authors: Bonadio Alessandro , Wenig Bernhard L. , Hockla Alexandra , Radisky Evette S. , Shifman Julia M.
Published: December 2022

Matrix metalloproteinases (MMPs) are key drivers of various diseases, including cancer. While several antibodies against MMPs are in development, our goal is to construct therapeutic anti-MMP inhibitors based on a natural broad MMP inhibitor, tissue inhibitor of metalloproteinases-2 (N-TIMP2). To confer high binding specificity toward one MMP type, we extend one of the N-TIMP2 loops, allowing it to interact with the non-conserved MMP surface. Multiple computational designs of the loop were used to design a focused library for yeast surface display, which was sorted for high binding to the target MMP-14 and low binding to off-target MMP-3. Deep sequencing of the two selected populations followed by comparative data analysis was used to identify the most promising variants, which were expressed, purified, and tested for inhibition of MMP-14 and off-target MMPs. Our best N-TIMP2 variant exhibited 29 pM binding affinity to MMP-14 and 2.4 µM affinity to MMP-3, 7500-fold more specific than WT N-TIMP2. Furthermore, the variant inhibited cell invasion with increased potency relative to WT N-TIMP2 in two breast cancer cell lines. We obtained the engineered variant high-accuracy model by including NGS data as input to AlphaFold multiple sequence alignment (MSA). Modeling results together with experimental mutagenesis demonstrate that the loop packs tightly against non-conserved residues on MMP-14 and clashes with MMP-3. This study demonstrates that introduction of loop extensions into inhibitors to stretch to the non-conserved surface of the target proteins is an attractive strategy for conferring high binding specificity in design of MMP inhibitors and other therapeutic proteins.
Antibiotic-induced dysbiosis does not potentiate the effect of lipopolysaccharide insult in male Wistar rats
Authors: Tejkalová Hana , Jakob Lea , Kvasnová Simona , Klaschka Jan , Sechovcová Hana , Mrázek Jakub , Páleníček Tomáš , Fliegerová Kateřina Olša
Published: December 2022

The present study investigated whether neonatal exposure to the proinflammatory endotoxin lipopolysaccharide (LPS) followed by antibiotic (ATB)-induced dysbiosis in early adulthood could induce schizophrenia-like behavioral changes in adult male rats. The combination of these two stressors resulted in decreased weight gain, but no significant behavioral abnormalities were observed. LPS treatment resulted in adult rats hypoactivity and induced anxiety-like behavior in the social recognition paradigm, but these behavioral changes were not exacerbated by ATB-induced gut dysbiosis. ATB treatment seriously disrupted the gut bacterial community, but dysbiosis did not affect locomotor activity, social recognition, and acoustic reactivity in adult rats. Fecal bacterial community analyzes showed no differences between the LPS challenge exposed/unexposed rats, while the effect of ATB administration was decisive regardless of prior LPS exposure. ATB treatment resulted in significantly decreased bacterial diversity, suppression of Clostridiales and Bacteroidales, and increases in Lactobacillales, Enterobacteriales, and Burkholderiales. The persistent effect of LPS on some aspects of behavior suggests a long-term effect of early toxin exposure that was not observed in ATB-treated animals. However, an anti-inflammatory protective effect of ATB cannot be assumed because of the increased abundance of pro-inflammatory, potentially pathogenic bacteria (Proteus, Suttrella) and the elimination of the bacterial familiesRuminococcaceaeandLachnospiraceae, which are generally considered beneficial for gut health.
Using principal component analysis to identify latent factors affecting cost and time overrun in public construction projects
Authors: Wyke Simon , Lindhard Søren Munch , Larsen Jesper Kranker
Published: December 2022

Purpose

Cost and time are two of the primary benchmarks in which construction projects are measured. A variety of factors, however, affect cost and time on construction projects, as identified in previous research. This has led to a need for better understanding how factors affecting cost and time overruns on public construction projects can be managed more efficiently. The purpose of this paper is to address these issues.

Design/methodology/approach

In this study 26 factors affecting cost and time overruns on construction projects were identified, through qualitative interviews with project managers from Danish governmental agencies and through a literature review. Through principal component analyses the 26 factors were subsequently narrowed down to four primary latent factors.

Findings

The identified four latent factors affecting cost and time overruns on public construction projects were lack of quality management, lack of project pre-planning, lack of user management and lack of project management.

Originality/value

Previous research has focussed on increasing knowledge by identifying and ranking factors affecting time and cost performance. This has led to the identification of an overwhelming number of factors to use for managing construction projects. The present research reduced the number of factors by clustering them into key latent factors responsible for most of the deviation in performance, narrowing the scope of construction cost and time management into a few tangible key focus areas. This supports and improves fast decision-making that is necessary in a changeable environment such as construction.
Indigenous knowledge, climate change and transformations of Gwadar fishing community
Authors: Ullah Shakir , Khan Usman , Begum Abida , Han Heesup , Mohamed Abdullah
Published: December 2022

Purpose

This paper explores the indigenous climate knowledge (ICK) of the Gwadar fishing community in Pakistan. The main purpose of this paper is to explore the accuracy of ICK and how climatic change brings changes to it and the social lives of local fishers.

Design/methodology/approach

Qualitative research methods, including participant observation, in-depth interviews and oral histories, were used to collect the data.

Findings

Finding from this long fieldwork shows that this fishing community has a harmonious relationship with nature and local ecology. Their knowledge of local ecology enables them to have equal access to natural resources, sustainable resource management, disaster risk reduction and strong social organization on the coast of Gwadar. Recently their deep relationship with local ecology and sociocultural organization has been disturbed due to huge climate changes caused by human manipulation of the environment. Their ability to foresee climatic events has been reduced. They are finding it impossible to estimate fish availability due to massive climate changes. Local communities are losing their traditional livelihoods and socioeconomic autonomy as a result of growing climate change. Climatic change adds to the existing poverty situation and increases political instability in the region.

Practical implications

The study suggests using the fishermen’s valuable indigenous knowledge of local ecology, climate and its ties to local traditions, culture and resource management for a scientific understanding of climate change and marine resource management in Gwadar, Pakistan.

Originality/value

This is an ethnographic study based on a long term field work. Fishing community is passing through catastrophic climatic changes in the region. This community has been ignored by both government and researchers to record their problems and bring them to academia and media. Therefore, this study will help them raise their voices.
Ambidextrous strategies in turbulent times: the experience of manufacturing SMEs during the COVID-19 pandemic
Authors: Bettiol Marco , Capestro Mauro , Di Maria Eleonora , Micelli Stefano
Published: December 2022

Purpose

The paper refers to the framework of ambidexterity to explain the strategic paths of manufacturing SMEs in turbulent times, by investigating SMEs' strategic reaction to the COVID-19 pandemic.

Design/methodology/approach

The authors adopted an inductive approach methodology. Using a qualitative research method, Italian manufacturing SMEs in different industries were interviewed to outline how they have faced the negative effects of the COVID-19 by considering the strategies implemented during the pandemic.

Findings

The study identifies three ambidextrous strategies for manufacturing SMEs to positively overcome the COVID-19 crisis: (1) playing different roles within the same market (business-to-business and business-to-consumer) simultaneously, (2) simultaneous entrance and management of multiple markets and (3) exploiting manufacturing knowledge for exploring product and business model innovation (simultaneous learning processes).

Research limitations/implications

Results enrich the theoretical discussion on ambidexterity and SMEs, by stressing the strategic dimension of ambidexterity and including a more fine-grained analysis of the different firm’ strategic paths in times of crisis.

Practical implications

The paper provides practical suggestions for manufacturing SMEs on how they can react during turbulent times and crises by implementing ambidextrous strategies also thanks to the use of digital technologies.

Originality/value

This paper contributes to outlining the conditions for SMEs' resilience in the international competitive context by highlighting the perspective of ambidexterity based on the analysis of multiple case studies from manufacturing industries.
The effect of short-term performance fluctuations on long-term performance: evidence from the English Premier League
Authors: Law Kuok Kei , Yeung Matthew C-H , Chan Jimmy H-T
Published: December 2022

Purpose

This paper aims to examine the effect of short-term performance fluctuations on long-term performance of football clubs.

Design/methodology/approach

This study did not develop any hypothesis for statistical testing. Instead, a database composing of 24 seasons of English Premier Club clubs’ performance was used to analyse for temporal fluctuations of club performance and examined whether such fluctuations would be substantiated in the long run.

Findings

Findings showed that club performance exhibited a non-unit root nature, which in turn suggested that clubs’ long-term performance was only temporally affected by short-term performance fluctuations, leading to the evidence that club performance tended to return to the club’s long-run equilibrium after experiencing temporary high or low positions.

Originality/value

Findings of this paper provide important information regarding the cost-benefit implications of the reactions of the club management to boost or rectify short-term performance fluctuations by, for example, replacing the club manager or head coach.
Fluid elastic instability and vortex shedding in finned tube arrays: the effects of tube material and fin density
Authors: Yadav Pravin Hindurao , Desai Sandeep R. , Mohanty Dillip Kumar
Published: December 2022

Purpose

The purpose of this paper is to present investigations on the significant influence of the tube material and fin density on fluid elastic instability and vortex shedding in a parallel triangular finned tube array subjected to water cross flow.

Design/methodology/approach

The experiment was conducted on finned tube arrays with a fin height of 6 mm and fin density of 3 fins per inch (fpi) and 9 fpi. A dedicated setup has been developed to examine fluid elastic instability and vortex shedding. Nine parallel triangular tube arrays with a pitch to tube diameter ratio of 1.78 were considered. The plain tube arrays, coarse finned tube arrays and fine finned tube arrays each of steel, copper and aluminium materials were tested. Plain tube arrays were tested to compare the results of the finned tube arrays having an effective tube diameter same as that of the plain tube.

Findings

A significant effect of fin density and tube material with a variable mass damping parameter was observed on the instability threshold. In the parallel triangular finned tube array subjected to water cross flow, a delay in the instability threshold was observed with an increase in fin density. For steel and aluminium tube arrays, the natural frequency is 9.77 Hz and 10.38 Hz, which is close to each other, whereas natural frequency of the copper tubes is 7.40 Hz. The Connors’ stability constant K for steel and aluminium tube arrays is 4.78 and 4.87, respectively, whereas it is 5.76 for copper tube arrays, which increases considerably compared to aluminum and steel tube arrays. The existence of vortex shedding is confirmed by comparing experimental results with Owen’s hypothesis and the Strouhal number and Reynolds number relationship.

Originality/value

This paper’s results contribute to understand the effect of tube materials and fin density on fluid elastic instability threshold of finned tube arrays subjected to water cross flow.
Digital inclusion and inequalities at work in the age of social media
Authors: Pekkala Kaisa
Published: December 2022

Advancements in digital communication technologies, such as social media, have transformed how individuals can interact inside and outside their organizations and participate in professional life. This qualitative study focuses on inclusion in the increasingly digitalized and interactive workplace. It adopts a managerial perspective and explores whether organizational members are perceived to have equal opportunities to participate and contribute in this novel environment. The research data consists of interviews with 24 managers in seven knowledge‐based organizations. The results show that both individual and organizational factors may become sources of inequality related to digital participation. The findings also emphasize that organizations have an important role in facilitating workers' digital inclusion. The paper contributes to the human resource management and digital inclusion literature and provides important managerial insights for organizations operating in the knowledge sector in particular.
Abelmoschus Manihot ameliorates the levels of circulating metabolites in diabetic nephropathy by modulating gut microbiota in non‐obese diabetes mice
Authors: Shi Ruiya , Tao Yingjun , Tang Haitao , Wu Chenhua , Fei Jingjin , Ge Haitao , Gu Harvest F. , Wu Jie
Published: December 2022

Huangkui capsule (HKC), a traditional Chinese medicine, has been used for medication of kidney diseases, including diabetic nephropathy (DN). The current study aimed to evaluate the effects of HKC in the modulation of gut microbiota and the amelioration of metabolite levels by using non‐obese diabetes (NOD) mice with DN. The microbiota from three parts of intestines (duodenum, ileum and colon) in NOD mice with and without HKC treatment were analysed using 16S rDNA sequencing techniques. Untargeted metabolomics in plasma of NOD mice were analysed with liquid mass spectrometry. Results showed that HKC administration ameliorated DN in NOD mice and the flora in duodenum were more sensitive to HKC intervention, while the flora in colon had more effects on metabolism. The bacterial genera such as Faecalitalea and Muribaculum significantly increased and negatively correlated with most of the altered metabolites after HKC treatment, while Phyllobacterium, Weissella and Akkermansia showed an opposite trend. The plasma metabolites, mainly including amino acids and fatty acids such as methionine sulfoxide, BCAAs and cis‐7‐Hexadecenoic acid, exhibited a distinct return to normal after HKC treatment. The current study thereby provides experimental evidence suggesting that HKC may modulate gut microbiota and subsequently ameliorate the metabolite levels in DN.
The Formation of the Jiaodong Gold Province
Authors: DENG Jun , WANG Qingfei , LIU Xuefei , ZHANG Liang , YANG Liqiang , YANG Lin , QIU Kunfeng , GUO Linnan , LIANG Yayun , MA Yao
Published: December 2022

Gold deposits in Jiaodong, termed Jiaodong‐type, are tectonically located in the southeastern margin of the North China Craton. Their major features are reviewed in this paper to highlight the differences between Jiaodong deposits and other genetic types of gold deposits. The mineralization was synchronized with asthenosphere upwelling indicated by syn‐ore OIB‐like mafic dike and large‐scale crustal thinning suggested by decrease of Sr/Y from pre‐ore to syn‐ore granites. Asthenosphere upwelling induced by the roll‐back of Paleo‐Pacific Plate drove partial melting of lithospheric mantle and devolatilization, which induced the release of the ore‐forming fluids. In concomitant with magmatic records, mineralization migrated from the western Jiaobei terrane (133–127 Ma) to the eastern Sulu orogenic belt (114–108 Ma), corresponding to the eastward roll‐back of Paleo‐Pacific Plate. Gold mineralization in Jiaodong formed in the transitions of ductile to brittle deformation, rapid to slow crustal uplift, and regional compression to extension. In the regional‐scale, the gold deposits in the Jiaobei terrane are mostly situated at intersections between NE‐trending faults and EW‐trending basement faults, and gold orebodies dominantly controlled by the lithologic contacts between Precambrian metamorphic rocks and Mesozoic granites. The mineralization was dominated by the disseminated‐veinlet ores related to quartz–sericite alteration in strong cataclasite‐breccia zone, with subsidiary thick quartz‐sulfide veins developed in secondary fault zones. The ore‐forming fluids belong to a H2O–CO2–NaCl±CH4system and show minor variations in salinity among different types of ore. Structure‐fluid feedback involving fluid‐rock reaction and hydrofracturing triggered the fluid phase separation and resultant gold deposition. The Jiaodong gold deposits are distinct from orogenic and intrusion‐related gold deposits in terms of tectonic setting, origin of ore‐forming fluids, and mechanism of gold deposition.
Extinctions, Morphological Gaps, Major Transitions, Stem Groups, and the Origin of Major Clades, with a Focus on Early Animals
Authors: XIAO Shuhai
Published: December 2022

Systematic extinctions can leave major morphological gaps between living crown‐group clades. Such morphological gaps would be perceived, from a neontological point of view, as major evolutionary transitions. In order to fill these morphological gaps and to map the evolutionary steps toward major evolutionary transitions, we need to integrate extinct stem‐group taxa in phylogenetic studies. However, the recognition of stem group has not been widely adopted in the study of early animal fossils, despite that all fossils are stem groups at one level or another. Part of the difficulty is that stem groups may not have all features that collectively diagnose the respective crown group, and they can have unique (autapomorphic) features, making them tantalizingly similar to and frustratingly different from the crown group (e.g., stem‐group eukaryotes can be prokaryotic and stem‐group animals can be protistan). The need to embrace stem groups and to implement the PhyloCode, in order to achieve phylogenetic clarity and to offer key paleontological insights into the origin and early animal evolution, is illustrated in debates on several controversial Ediacaran and Cambrian fossils.
Unresolved early post‐operative pain trajectory predicts moderate‐to‐severe persistent pain after breast cancer surgery—An observational cohort study
Authors: Leblanc Damien , Guichoux Arthur , Sail Marjorie , Boré François , Seegers Valérie , Espitalier Fabien
Published: December 2022

Background

Modelling acute post‐operative pain trajectories may improve the prediction of persistent pain after breast cancer surgery (PPBCS). This study aimed to investigate the predictive accuracy of early post‐operative pain (EPOP) trajectories in the development of PPBCS.

Materials & Methods

This observational study was conducted in a French Comprehensive Cancer Centre and included patients who underwent breast cancer surgery from December 2017 to November 2018. Perioperative and follow‐up data were obtained from medical records, and anaesthesia and perioperative charts. EPOP was defined as pain intensity during the first 24 h after surgery, and modelled by a pain trajectory. K‐means clustering method was used to identify patient subgroups with similar EPOP trajectories. The prevalence of moderate‐to‐severe PPBCS (numeric rating scale ≥4) was evaluated until 24 months after surgery.

Results

A total of 608 patients were included in the study, of which 18% (n = 108) and 9% (n = 52) reported mild and moderate‐to‐severe PPBCS, respectively. Based on EPOP trajectories, we were able to identify a low (64%, n = 388), resolved (30%, n = 182), and unresolved (6%, n = 38) pain group. Multivariate analysis identified younger age, axillary lymph node dissection, and unresolved EPOP trajectory as independent risk factors for moderate‐to‐severe PPBCS development. When compared to patients reporting mild PPBCS, moderate‐to‐severe PPBCS patients experienced significantly more neuropathic pain features, pain‐related interference, and delayed opioid cessation.

Conclusion

EPOP trajectories can distinguish between resolved and unresolved acute pain after breast cancer surgery, allowing early identification of patients at risk to develop significant PPBCS.
Wearable device for prevention of postoperative and post‐discharge hypoxemia: A randomized pilot trial
Authors: Li Kai , Saab Remie , Bravo Mauro , Mascha Edward J. , Han Yanyan , Nault Rod , Olson Lloyd , Sessler Daniel I.
Published: December 2022

Background

The Oxalert Enhanced Pulse Oximeter (EPO) is a wearable device that detects and alerts patients to hypoxemia. In a preplanned pilot trial, we estimated the effect of continuous saturation monitoring with patient alerts on in‐hospital and post‐discharge saturation; we further assessed the feasibility of the intervention.

Methods

Noncardiac surgical patients were randomized to either the Oxalert with patient alerts (Monitor + Alert, N = 25) or the Oxalert without patient alerts (Monitor Only, N = 24). Monitoring continued during hospitalization for up to 6 days and for 24 h after hospital discharge. Patients in each group were compared on time‐weighted average (TWA) SpO2 <90% (%) and area under SpO2 <90% (% * min) in‐hospital and after discharge using the Wilcoxon rank sum test, with the treatment effect median difference and 95% confidence interval (CI) estimated using the Hodges–Lehmann estimator of location shift.

Results

We enrolled ≥2 patients per week, for a total of 49 patients in whom recording were obtained for a median [quartiles] of 91 [85, 95]% of the time in hospital. In‐hospital, TWA SpO2 <90% was a median [quartiles] of 0.11 [0.03, 0.25]% for Monitor + Alert and 0.29 [0.04, 0.71]% for Monitor‐Only patients, with estimated median difference (95% CI) of −0.1 (−0.4, 0)%, p = .120. In hospital, the area under the curve (AUC) SpO2 <90% was a median [quartiles] of 635 [204, 1513] % * min for Monitor + Alert and 1260 [117, 5278] % * min for Monitor‐Only patients, with estimated median difference (95% CI) of −407 (−1816, 208) % * min, p = .349. Post‐discharge, the estimated median difference (95% CI) was only −0.1 (−0.2, 0) %, p = .307.

Conclusions

The Oxalert system was well tolerated in both groups and enrollment was strong. Patients randomized to active Oxalert systems experienced half as many postoperative desaturation events while hospitalized, although the difference was not statistically significant in this small pilot trial. In contrast, the Oxalert system did not reduce post‐discharge desaturation. Detecting postoperative deterioation in surgical patients after they arrive on regular hospital wards, and even after they have been discharged home, can potentially facilitate necessary “rescue” interventions. Wearable devices assessing vital signs, including oxygenation, are a practical requirement. In this pilot study, a wearable pulse oximeter, with and without hypoxemia alarms, was tested for feasibility and acceptability for signal collection in postoperative cases, including at home. Results indicate that a full‐scale trial is warranted to test for possible clinical benefit with this type of “wearable” where late postoperative hypoxia could be a concern. The trial was registered at ClincialTrial.gov (NCT04453722).
Positive oral health outcomes: A partnership model improves care in a rural Indigenous community
Authors: Mangoyana Clare , March Sandra , Lalloo Ratilal , Walsh Laurence J.
Published: December 2022

Objective

The purpose of this study was to explore the benefits of a partnership between a university dental school and a Community Controlled Health Service, specifically in relation to improving the oral health of an underserved rural Indigenous community. We sought community opinions on health and social outcomes arising from the service provided by the dental student clinical outplacement.

Setting

In Dalby, Queensland.

Participants

In total, 38 participants in five focus groups were representative of local Indigenous community Elders, community health support group members and management and staff.

Design

A descriptive qualitative study employing semi‐structured audio‐recorded focus group discussions conducted with purposefully selected Indigenous community groups to explore participant views and experience of the partnership model. Qualitative data were analysed using thematic content analysis.

Results

The Indigenous community representatives expressed positive benefit in both their general and oral health awareness, in improved access to dental care provided in their own safe space, while they were pleased to assist with students' learning. They viewed the partnership as mutually beneficial. Suggestions for enhancement of the oral health service were also offered.

Conclusion

This partnership between a university and a Community Controlled Health Service provides sustainable positive social and health benefits for the targeted Indigenous community and for the wider local population, while simultaneously providing enhanced educational benefits for students on clinical outplacement. Translation and uptake of this successful model of care would benefit both underserved communities and dental and other health care professional educators worldwide.
Squalene epoxidase promotes hepatocellular carcinoma development by activating STRAP transcription and TGF‐β/SMAD signalling
Authors: Zhang Zhirui , Wu Wei , Jiao Hao , Chen Yuzhong , Ji Xiaojun , Cao Jing , Yin Fangzhou , Yin Wu
Published: December 2022

Background and Purpose

Squalene epoxidase (SQLE) is a key enzyme involved in cholesterol biosynthesis, but growing evidence also reveals that SQLE is abnormally expressed in some types of malignant tumours, even though the underlying mechanism remains poorly understood.

Experimental Approach

Bioinformatics analysis and RNA sequencing were applied to detect differentially expressed genes in clinical hepatocellular carcinoma (HCC). MTT, colony formation, AnnexinV‐FITC/PI, EdU, wound healing, transwell, western blot, qRT‐PCR, IHC, F‐actin, RNA‐sequencing, dual‐luciferase reporters, and H&E staining were used to investigate the pharmacological effects and possible mechanisms of SQLE.

Key Results

SQLE expression was specifically elevated in HCC, correlating with poor clinical outcomes. SQLE significantly promoted HCC growth, epithelial–mesenchymal transition, and metastasis both in vitro and in vivo. RNA sequencing and functional experiments revealed that the protumourigenic effect of SQLE on HCC was closely related to the activation of TGF‐β/SMAD signalling, but the stimulatory effect of SQLE on TGF‐β/SMAD signalling and HCC development is critically dependent on STRAP. SQLE expression is well correlated with STRAP in HCC, and further, to amplify TGF‐β/SMAD signalling, SQLE even transcriptionally increased STRAP gene expression mediated by AP‐2α. Finally, as a chemical inhibitor of SQLE, NB‐598 markedly inhibited HCC cell growth and tumour development.

Conclusions and Implications

Taken together, SQLE serves as a novel oncogene in HCC development by activating TGF‐β/SMAD signalling. Targeting SQLE could be useful in drug development and therapy for HCC.
Talking with machines: Can conversational technologies serve as children's social partners?
Authors: Xu Ying
Published: December 2022

Back‐and‐forth conversations with others are vital for children's development in the early years. While children's conversation partners have traditionally been their parents, teachers, and peers, recent advances in artificial intelligence have led to the introduction of machines that understand human speech and generate natural responses, and thus can engage children in conversations. As these technologies become increasingly ubiquitous in children's lives, questions arise as to how they might affect children's development: How do children interact with, perceive, and learn from conversational technologies? Can these technologies serve as children's social partners? In this article, I detail what we know about these topics and discuss the possible implications of conversational technologies for children's shifting media landscape. I also suggest research agendas that can unpack the complex interplay among children, their social contexts, and conversational technology.
Holocaust communication, attachment orientation and distress among descendants of female holocaust survivors
Authors: Lishner Freud Eve , Berant Ety
Published: December 2022

The multiple studies that have examined the transgenerational transmission of Holocaust trauma from survivors to their descendants have yielded inconsistent results. These can be attributed to differences in assessment tools and to individual differences between survivors, such as their specific experiences during the Holocaust. This study examined the differences between daughters and granddaughters of female Holocaust survivors (HS) of concentration camps (CCS) versus survivors of other circumstances (ghettos, concealment, etc.; OCCS) in terms of communication about their mothers' or grandmothers' Holocaust trauma (Holocaust communication), their attachment orientations, and their psychological distress. The sample was composed of 79 dyads of daughters of HS and their own daughters, divided into two groups according to the survivors' Holocaust experiences (CCS—47 dyads; OCCS—32 dyads). The findings indicated that daughters of CCS reported a higher number of conversations about the Holocaust with their mothers, perceived their mothers as more distant during Holocaust communication, and reported more guilt feelings than daughters of OCCS. Holocaust communication between daughters and granddaughters was characterized by shorter conversations, and granddaughters perceived their mothers as sadder in the CCS group than in the OCCS group. No difference between groups was found in Holocaust communication between survivors and their granddaughters. No difference was found between groups in their psychological distress. The granddaughters of CCS scored higher on attachment anxiety than the other group. Most of the significant differences between groups were linked to subtle differences in the characteristics of communication and in the inter‐personal sphere.