bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized Arterial Line Artifact Identification Algorithm Cleans High-Frequency Arterial Line Data With High Accuracy in Critically Ill Patients
Authors: Khan Jasmine M. , Maslove David M. , Boyd J. Gordon
Published: October 2023

OBJECTIVES:

High-frequency data streams of vital signs may be used to generate individualized hemodynamic targets for critically ill patients. Central to this precision medicine approach to resuscitation is our ability to screen these data streams for errors and artifacts. However, there is no consensus on the best method for data cleaning. Our goal was to determine whether an error-checking algorithm developed for intraoperative use could be applied to high volumes of arterial line data in an ICU population.

DESIGN:

Multicenter observational study.

SETTING:

ICUs across Ontario, Canada.

PATIENTS:

Nested cohort of ICU patients with shock and/or respiratory failure requiring invasive mechanical ventilation.

INTERVENTIONS:

High-frequency blood pressure data was analyzed. Systolic, diastolic, and mean arterial pressure minute averages were calculated. For manual analysis, a trained researcher retrospectively reviewed mean arterial pressure data, removing values that were deemed nonphysiological. The algorithm was implemented and identified artifactual data.

MEASUREMENTS AND MAIN RESULTS:

Arterial line data was extracted from 15 patients. A trained researcher manually reviewed 40,798 minute-by-minute data points, then subsequently analyzed them with the algorithm. Manual review resulted in the identification of 119 artifacts (0.29%). The optimized algorithm identified 116 (97%) of these artifacts. Five hundred thirty-seven data points were erroneously removed or modified. Compared with manual review, the modified algorithm incorporating absolute thresholds of greater than 30 and less than 200 mm Hg had 97.5% sensitivity, 98.7% specificity, and a Matthew correlation coefficient of 0.41.

CONCLUSIONS:

The error-checking algorithm had high sensitivity and specificity in detecting arterial line blood pressure artifacts compared with manual data cleaning. Given the growing use of large datasets and machine learning in critical care research, methods to validate the quality of high-frequency data is important to optimize algorithm performance and prevent spurious associations based on artifactual data.
Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19*
Authors: Janssen Matthijs L. , Türk Yasemin , Baart Sara J. , Hanselaar Wessel , Aga Yaar , van der Steen-Dieperink Mariëlle , van der Wal Folkert J. , Versluijs Vera J. , Hoek Rogier A.S. , Endeman Henrik , Boer Dirk P. , Hoiting Oscar , Hoelters Jürgen , Achterberg Sefanja , Stads Susanne , Heller-Baan Roxane , Dubois Alain V.F. , Elderman Jan H. , Wils Evert-Jan ,   on behalf of the Dutch HFNO COVID-19 Study Group
Published: October 2023

OBJECTIVE:

High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards.

DESIGN:

Prospective observational multicenter pragmatic study.

SETTING:

Respiratory wards and ICUs of 10 hospitals in The Netherlands.

PATIENTS:

Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort (n = 214 patients) was 53% and 60% in ward and ICU starters, respectively (p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p < 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pao
2:Fio
2 ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values > 0.05).

CONCLUSIONS:

In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.
Screening for Comorbidity of Sleep Disorders in Career Firefighters
Authors: Hamilton Nancy A. , Russell Julia , Hamadah Kareem , Youngren Westley , Toon Addie , Nguyen Thu A. , Joles Kevin
Published: October 2023

Background

The purpose of this study was to assess the prevalence and sequelae of insomnia, obstructive sleep apnea (OSA), and comorbid OSA and insomnia (COMISA).

Method

In the morning, after a shift end, Midwest career firefighters (N = 89) in a midsized city completed an electronic battery of questionnaire to screen for OSA, daytime sleepiness, insomnia, presleep arousal, nightmares, mental and physical health symptoms, and a one-night sleep diary.

Results

Prevalence of firefighters exceeding screening thresholds: OSA: 54%; insomnia: 30%; COMISA: 17%; four or more nightmares per month: 15%. Firefighters who met criteria for COMISA had shorter total sleep time, less restful and worse sleep quality, higher depression and anxiety symptoms, and presleep arousal symptoms than firefighters without self-reported sleep problems.

Conclusions

Many firefighters are at elevated risk of individual behavioral sleep disorders, COMISA, and daytime dysfunction.
Relationship between uric acid to albumin ratio and in-stent restenosis in patients with coronary artery disease undergoing drug-eluting stenting
Authors: Liu Wenquan , Ding Kun , Bao Jiaqi , Hu Yilan , Gui Yang , Ye Lifang , Wang Lihong
Published: October 2023

Background

In-stent restenosis (ISR) in patients undergoing percutaneous coronary intervention (PCI) to treat coronary artery disease (CAD) is an urgent issue in clinical practice. Recent studies have highlighted uric acid-albumin ratio (UAR) as a new marker for evaluating inflammation and oxidative stress, capable of predicting cardiovascular ailments. We aimed to examine the correlation between UAR levels and ISR in patients who underwent drug-eluting stent (DES) implantation.

Methods

We included 503 patients with CAD who underwent initial DES implantation and angiography during the follow-up period. Based on coronary angiographic findings, the patients were categorized into ISR (n = 73) and non-ISR groups (n = 430). Before angiography, laboratory parameters were measured for all enrolled patients. To ascertain the influential factors linked to ISR, multivariate logistic regression analysis was performed. The predictive capability of UAR in determining ISR was assessed using receiver operating characteristic (ROC) curve analysis. Statistical significance was set at P < 0.05.

Results

Multivariate logistic regression analysis revealed that diabetes mellitus, stent length, UAR, albumin levels, and C-reactive protein levels independently predicted ISR. ROC curve analysis revealed that UAR had an area under the curve of 0.767 (95% CI: 0.709 – 0.826) for predicting ISR and demonstrated that UAR outperformed the individual predictive abilities of uric acid and albumin for ISR.

Conclusion

UAR was associated with ISR in patients with CAD undergoing PCI with DES implantation. Moreover, ROC curve analysis demonstrated that UAR exhibited superior predictive accuracy for ISR compared with evaluating uric acid and albumin levels separately.
Delayed tranexamic acid after traumatic brain injury impedes learning and memory: Early tranexamic acid is favorable but not in sham animals
Authors: Culkin Matthew C. , Coons Michael , Bele Priyanka , Thaploo Advait , Georges Anastasia P. , Anderson Erin , Browne Kevin D. , Jacovides Christina , Santos Patricia , Kaplan Lewis J. , Meaney David F. , Smith Douglas H. , Pascual Jose L.
Published: October 2023

BACKGROUND

Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours postinjury. We hypothesized that early (1 hour post-TBI) but not late (24 hours post-TBI) TXA administration improves cognitive recovery for 14 days.

METHODS

CD1 male mice (n = 25) were randomized to severe TBI (injury [I], by controlled cortical impact) or sham craniotomy (S) followed by intravenous saline at 1 hour (placebo [P1]) or 30 mg/kg TXA at 1 hour (TXA1) or 24 hours (TXA24). Daily body weights, Garcia Neurological Test scores, brain/lung water content, and Morris water maze exercises quantifying swimming traffic in the platform quadrant (zone [Z] 1) and platform area (Z5) were recorded for up to 14 days.

RESULTS

Among injured groups, I-TXA1 demonstrated fastest weight gain for 14 days and only I-TXA1 showed rapid (day 1) normalization of Garcia Neurological Test (p = 0.01 vs. I-P1, I-TXA24). In cumulative spatial trials, compared with I-TXA1, I-TXA24 hindered learning (distance to Z5 and % time in Z1, p < 0.05). Compared with I-TXA1, I-TXA24 showed poorer memory with less Z5 time (0.51 vs. 0.16 seconds, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S-TXA1) displayed faster weight gain but inferior learning and memory.

CONCLUSION

Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, although administration 24 hours postinjury consistently impairs cognitive recovery. Tranexamic acid in sham animals may lead to adverse effects on cognition.
Pipeline for RNA sequencing data analysis by combination of Nextflow and R
Authors: Qu Jia-Hua
Published: October 2023

With the development of high-throughput technologies, RNA sequencing (RNA-seq) has become a widely used technology in biological studies and thus a large number of RNA-seq data are emerging and remain to be analyzed. Although there are many different options for analysis methods and tools, a unified pipeline for RNA-seq data analysis is always necessary for a laboratory. Given the update of new methods and tools, I summarized my customized analysis codes to generate an updated pipeline for RNA-seq data analysis. During aging, gene mutations accumulate, and hormone regulation is disrupted, which may exacerbate age-related diseases. Therefore, we generated a dataset from mice with a gene mutation or not and under different hormone treatments to study the effects of two factors, i.e., hormone and gene mutation, on the transcriptome. Based on the Nextflow nf-core rnaseq pipeline, this project established this pipeline consisting of three stages: (1) upstream analysis containing quality control of fastq files before and after trimming, trimming, alignment, and quantification; (2) midstream analysis containing count normalization, differentially expressed genes analysis, and visualization via boxplot, PCA, t-SNE, sample distance heatmap, MA plot, volcano plot, and gene expression heatmap; and (3) downstream analysis containing functional enrichments of KEGG pathways and GO terms. Results showed distinct effects of the single factor as well as interactive effects of the two factors. Codes are also provided for readers who want to customize their analysis pipeline adapted from this pipeline easily.
The Efficacy of Multimodal Physiotherapy versus Usual Care in Chronic Whiplash-Associated Disorders With Facet-Mediated Pain Undergoing Platelet Rich Plasma treatment: A Series of Single Case Experimental Designs
Authors: Smith Ashley , Gupta Arun , Stone Jacqui , Habberfield Jeff , Schneider Geoff
Published: October 2023

Purpose

Chronic whiplash-associated disorders (WAD) is a heterogeneous condition with limited effective treatment options available. This study evaluated the effectiveness of multimodal physiotherapy versus usual care in chronic WAD with facet-mediated pain receiving platelet-rich plasma (PRP) injections to determine if pain interference and confidence completing activities in the presence of neck pain could be improved.

Materials and Methods

A multiple-baseline, single-case experimental design was used to evaluate the 6-week effect of physiotherapy or usual care in two groups of three participants each.

Results

All six participants demonstrated a significant reduction in pain interference, and three participants showed improved confidence to perform daily activities when in pain. Weighted Tau-U demonstrated a significant reduction of pain interference with large to very large effect sizes (> 0.75) for both interventions in all participants irrespective of treatment allocation with no significant group difference demonstrated. Similar effects were demonstrated for the confidence to perform daily activities with neck pain (ES > 0.46), although this was only evident in three participants (two PT and one UC). Generalization measures also showed improvements in pain and disability, psychological and quality of life outcomes. No adverse events were reported.

Conclusions

Both physiotherapy and usual care demonstrated improvements in pain interference and confidence to perform activities of daily living with neck pain in people with chronic WAD following cervical facet joint PRP.

Trial Registration

The trial was registered withClinicalTrials.gov(Protocol Number:NCT03949959)
Probing Human Heart TCA Cycle Metabolism and Response to Glucose Load using Hyperpolarized [2-13C]Pyruvate MR Spectroscopy
Authors: Chen Hsin-Yu , Gordon Jeremy W. , Dwork Nicholas , Chung Brian T. , Riselli Andrew , Sivalokanathan Sanjay , Bok Robert A. , Slater James B. , Vigneron Daniel B. , Abraham M. Roselle , Larson Peder E.Z.
Published: October 2023

Abstract Summary

Introduction

The normal heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid (FA) oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2-13C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes. This study aimed to develop methods, demonstrate feasibility for [2-13C]pyruvate MRI in the human heart for the first time, and assess cardiac metabolic flexibility.

Methods

Good Manufacturing Practice [2-13C]pyruvic acid was polarized in a 5T polarizer for 2.5-3 hours. Following dissolution, QC parameters of HP pyruvate met all safety and sterility criteria for pharmacy release, prior to administration to study subjects. Three healthy subjects each received two HP injections and MR scans, first under fasting conditions, followed by oral glucose load. A 5cm axial slab-selective spectroscopy approach was prescribed over the left ventricle and acquired at 3s intervals on a 3T clinical MRI scanner.

Results

The study protocol which included HP substrate injection, MR scanning and oral glucose load, was performed safely without adverse events. Key downstream metabolites of [2-13C]pyruvate metabolism in cardiac myocytes include the glycolytic derivative [2-13C]lactate, TCA-associated metabolite [5-13C]glutamate, and [1-13C]acetylcarnitine, catalyzed by carnitine acetyltransferase (CAT). After glucose load,13C-labeling of lactate, glutamate, and acetylcarnitine from13C-pyruvate increased by 39.3%, 29.5%, and 114%, respectively in the three subjects, that could result from increases in lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), and CAT enzyme activity as well as TCA cycle flux (glucose oxidation).

Conclusions

HP [2-13C]pyruvate imaging is safe and permits non-invasive assessment of TCA cycle intermediates and the acetyl buffer, acetylcarnitine, which is not possible using HP [1-13C]pyruvate. Cardiac metabolite measurement in the fasting/fed states provides information on cardiac metabolic flexibility and the acetylcarnitine pool.

Graphical Abstract
ACSL4 activity drives TNBC metastasis by positively regulating Histone H3 Acetylation mediated SNAIL expression
Authors: Sinha Abhipsa , Saini Krishan Kumar , Tripathi Kiran , Khan Muqtada Ali , Satrusal Saumya Ranjan , Verma Ayushi , Mandal Biswajit , Rai Priyanka , Meena Sanjeev , Nengroo Mushtaq Ahmad , Singh Manish Pratap , Bhushan Namratha Shashi , Vasudevan Madavan , Singhai Atin , Singh Kulranjan , Mishra Anand Kumar , Datta Dipak
Published: October 2023

Triple-Negative Breast Cancer (TNBC) has profound unmet medical need globally for its devastating clinical outcome associated with rapid metastasis and lack of targeted therapies. Recently, lipid metabolic reprogramming has emerged as a major driver of breast cancer metastasis. Here, we unveil a strong association between the heightened expression of fatty acid metabolic enzyme, acyl-CoA synthetase 4 (ACSL4) and TNBC, which is primarily attributed by the selective absence of progesterone receptor (PR). Loss of ACSL4 function, either through genetic ablation or pharmacological inhibition significantly reduces metastatic potential of TNBC. Global transcriptome analysis reveals that ACSL4 activity markedly influences the gene expression pattern associated with TNBC migration. Mechanistically, ACSL4 alters fatty acid oxidation (FAO) and cellular acetyl-CoA levels, leading to the hyper-acetylation of particularly H3K27Ac and H3K9Ac marks resulting in overexpression of SNAIL during the course of TNBC metastatic spread to lymph node and lungs. Further, human TNBC metastasis exhibits positive correlation between ACSL4 and SNAIL expression. Altogether, our findings provide new molecular insights regarding the intricate interplay between metabolic alterations and epigenetic modifications, intertwined to orchestrate TNBC metastasis and posit a rational understanding for the development of ACSL4 inhibitors as a targeted therapy against TNBC.
Polinton-like Viruses Associated with Entomopoxviruses Provide Insight into Replicon Evolution
Authors: Barth Zachary K. , Hicklin Ian , Thézé Julien , Takatsuka Jun , Nakai Madoka , Herniou Elisabeth A. , Brown Anne M. , Aylward Frank O.
Published: October 2023

Polinton-like viruses (PLVs) are a diverse group of small integrative dsDNA viruses that infect diverse eukaryotic hosts. Many PLVs are hypothesized to parasitize viruses in the phylumNucleocytoviricotafor their own propagation and spread. Here we analyze the genomes of novel PLVs associated with the occlusion bodies of entomopoxvirus (EV) infections of two separate lepidopteran hosts. The presence of these elements within EV occlusion bodies suggests that they are the first known hyperparasites of poxviruses. We find that these PLVs belong to two distinct lineages that are highly diverged from known PLVs. These PLVs possess mosaic genomes, and some essential genes share homology with mobile genes within EVs. Based on this homology and observed PLV mosaicism, we propose a mechanism to explain the turnover of PLV replication and integration genes.
T cells Use Focal Adhesions to Pull Themselves Through Confined Environments
Authors: Caillier Alexia , Oleksyn David , Fowell Deborah J. , Miller Jim , Oakes Patrick W.
Published: October 2023

Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical composition. Their migration has classically been defined as amoeboid under the assumption that it is integrin-independent. Here we show that activated primary Th1 T cells require both confinement and extracellular matrix protein to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal focal adhesions, such as integrins, talin, and vinculin. These focal adhesions, furthermore, localize to sites of contractile traction stresses, enabling T cells to pull themselves through confined spaces. Finally, we show that Th1 T cell preferentially follows tracks of other T cells, suggesting that these adhesions are modifying the extracellular matrix to provide additional environmental guidance cues. These results demonstrate not only that the boundaries between amoeboid and mesenchymal migration modes are ambiguous, but that integrin-mediated adhesions play a key role in T cell motility.

Graphical Abstract
Electrophysiological characterisation of iPSC-derived human β-like cells and anSLC30A8disease model
Authors: Jaffredo Manon , Krentz Nicole A. J. , Champon Benoite , Duff Claire E. , Nawaz Sameena , Beer Nicola , Honore Christian , Clark Anne , Rorsman Patrik , Lang Jochen , Gloyn Anna L. , Raoux Matthieu , Hastoy Benoit
Published: October 2023

iPSC-derived human β-like cells (BLC) hold promise for both therapy and disease modelling, but their generation remains challenging and their functional analyses beyond transcriptomic and morphological assessments remain limited. Here, we validate an approach using multicellular and single cell electrophysiological tools to evaluate BLCs functions. The Multi-Electrode Arrays (MEAs) measuring the extracellular electrical activity revealed that BLCs are electrically coupled, produce slow potential (SP) signals like primary β-cells that are closely linked to insulin secretion. We also used high-resolution single-cell patch-clamp measurements to capture the exocytotic properties, and characterize voltage-gated sodium and calcium currents. These were comparable to those in primary β and EndoC-βH1 cells. The KATPchannel conductance is greater than in human primary β cells which may account for the limited glucose responsiveness observed with MEA. We used MEAs to study the impact of the type 2 diabetes protectiveSLC30A8allele (p.Lys34Serfs*50) and found that BLCs with this allele have stronger electrical coupling. Our data suggest that with an adapted approach BLCs from pioneer protocol can be used to evaluate the functional impact of genetic variants on β-cell function and coupling.

Article highlights

Why did we undertake this study?

iPSC-derived beta like cells (BLCs) from pioneering protocols are known for variable β-cell functionality and mixed cell populations which greatly limits downstream functional assessment. To overcome this challenge, we used electrophysiological tools to provide a detailed functional assessment of BLCs. We then wanted to apply this approach to identify additional functional differences from BLCs carrying a protective Type 2 DiabetesSLC30A8allele.

What is the specific question(s) we wanted to answer?

Can an electrophysiological approach provide detailed functional characterisation of iPSC-derived BLCs? Is this approach sensitive enough to capture functional differences resulting fromSLC30A8loss of function (lof)?

What did we find?

We found that BLCs generated from pioneer protocol shared electrophysiological features with human pancreatic β-cells, and that a T2D-protectiveSLC30A8lof allele improves the electrical coupling activity of human β-cells.

What are the implications of our findings?

Our findings validate the use of intra- and extra-cellular electrophysiology to assess and monitor the functions of BLCs. Our approach opens the perspective of using MEAs to live-monitor the differentiation quality of iPSC-derived BLCs and to determine the functional consequences of diabetes-associated variants.
VIBES: A Workflow for Annotating and Visualizing Viral Sequences Integrated into Bacterial Genomes
Authors: Copeland Conner J. , Roddy Jack W. , Schmidt Amelia K. , Secor Patrick R. , Wheeler Travis J.
Published: October 2023

Bacteriophages are viruses that infect bacteria. Many bacteriophages integrate their genomes into the bacterial chromosome and become prophages. Prophages may substantially burden or benefit host bacteria fitness, acting in some cases as parasites and in others as mutualists, and have been demonstrated to increase host virulence. The increasing ease of bacterial genome sequencing provides an opportunity to deeply explore prophage prevalence and insertion sites. Here we present VIBES, a workflow intended to automate prophage annotation in complete bacterial genome sequences. VIBES provides additional context to prophage annotations by annotating bacterial genes and viral proteins in user-provided bacterial and viral genomes. The VIBES pipeline is implemented as a Nextflow-driven workflow, providing a simple, unified interface for execution on local, cluster, and cloud computing environments. For each step of the pipeline, a container including all necessary software dependencies is provided. VIBES produces results in simple tab separated format and generates intuitive and interactive visualizations for data exploration. Despite VIBES’ primary emphasis on prophage annotation, its generic alignment-based design allows it to be deployed as a general-purpose sequence similarity search manager. We demonstrate the utility of the VIBES prophage annotation workflow by searching for 178 Pf phage genomes across 1,072Pseudomonasspp. genomes. VIBES software is available athttps://github.com/TravisWheelerLab/VIBES.
Universal conditions for establish continuous cell cultures in ray-finned fishes
Authors: Cardoso Adauto Lima , Nascimento Oliveira Jordana Inácio , Climaco João Pedro Silva , Venturelli Natália Bortholazzi , Moreira Camila do Nascimento , Martins Cesar
Published: October 2023

Ray-finned fishes represent the most diverse vertebrate lineage and show extensive variations in physiology, ways of life and adaptations to marine and freshwater environments. Actinopterygii are largely exploited for human consumption and several species have been established as biological models. The in vitro culture of cells is fundamental for several fields of biological research, being an alternative for studies that use animals, since it mimics the cellular homogeneity of the original organisms beyond the advantage of reducing the variability of responses observed under in vivo conditions. In the case of fish cell cultures, besides being an important biomedical tool, they can offer important contributions to aquaculture and fish conservation. Hundreds of fish cell lines have been established using specific methods for each cell type and species. Here we describe an optimized protocol for obtaining cell cultures from the caudal fin of a wide range of ray-finned fishes including marine and freshwater species. The proliferative potential of these cultures makes them useful for several applications and the minimally invasive feature of this protocol makes it suitable for use in conservation plans.
Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice
Authors: Traughber C. Alicia , Timinski Kara , Prince Ashutosh , Bhandari Nilam , Neupane Kalash , Khan Mariam R , Opoku Esther , Opoku Emmanuel , Brubaker Gregory , Nageshwar Kanuri , Ertugral Elif G. , Naggareddy Prabha , Kothapalli Chandrasekhar R. , Smith Jonathan D. , Gulshan Kailash
Published: October 2023

Pyroptosis executor Gasdermin (GsdmD) promotes atherosclerosis in mice and humans. Disulfiram (DSF) was recently shown to potently inhibit GsdmD, but the in-vivo efficacy and mechanism of DSF’s anti-atherosclerotic activity is yet to be explored. We used human/mouse macrophages and a hyperlipidemic mouse model of atherosclerosis to determine DSF anti-atherosclerotic efficacy and mechanism. DSF-fed hyperlipidemic apoE-/-mice showed significantly reduced IL-1β release upon in-vivo Nlrp3 inflammasome assembly and showed smaller atherosclerotic lesions (∼27% and 29% reduction in males and females, respectively). The necrotic core area was also smaller (∼50% and 46% reduction in DSF-fed males and females, respectively). DSF induced autophagy in macrophages, hepatocytes/liver, and in atherosclerotic plaques. DSF modulated other atheroprotective pathways such as efferocytosis, phagocytosis, and gut microbiota. DSF-treated macrophages showed enhanced phagocytosis/efferocytosis, with a mechanism being a marked increase in cell-surface expression of efferocytic receptor MerTK. Atomic-force microscopy analysis revealed altered biophysical membrane properties of DSF treated macrophages, showing increased ordered-state of the plasma membrane and increased adhesion strength. Furthermore, the 16sRNA sequencing of DSF-fed hyperlipidemic mice showed highly significant enrichment in atheroprotective gut microbiotaAkkermansiaand a reduction in atherogenicRomboutsiaspecies. Taken together, our data shows that DSF can simultaneously modulate multiple atheroprotective pathways, and thus may serve as novel adjuvant therapeutic to treat atherosclerosis.
The landscape of genomic structural variation in Indigenous Australians
Authors: Reis Andre L.M. , Rapadas Melissa , Hammond Jillian M. , Gamaarachchi Hasindu , Stevanovski Igor , Kumaheri Meutia Ayuputeri , Chintalaphani Sanjog R. , Dissanayake Duminda S.B. , Siggs Owen M. , Hewitt Alex W. , Llamas Bastien , Brown Alex , Baynam Gareth , Mann Graham J. , Hermes Azure ,   The National Centre for Indigenous Genomics, Patel Hardip R. , Deveson Ira W.
Published: October 2023

Indigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference databases. Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here, we apply population-scale whole genome long-read sequencing to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large indels (20-49bp;n=136,797) and structural variants (SVs; ≥50bp;n=159,912), the majority of which are composed of tandem repeat or interspersed mobile element sequences (90%) and have not been previously annotated (73%). A large fraction of SVs appear to be exclusive to Indigenous Australians (>30%) and the majority of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short-tandem repeats (STRs) throughout the genome to characterise allelic diversity at 50 known disease loci, uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among STR sequences. Our study sheds new light on the dimensions, diversity and evolutionary trajectories of genomic structural variation within and beyond Australia.
TheAspergillus fumigatus maiAgene contributes to cell wall homeostasis and fungal virulence
Authors: Guruceaga X , Perez-Cuesta U , Martin-Vicente A , Pelegri-Martinez E , Thorn H , Cendon-Sanchez S , Xie J , Nywening A , Ramirez-Garcia A , Fortwendel JR , Rementeria A
Published: October 2023

In this study, two distinctin vitroinfection models ofAspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubatedAspergillusuncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously publishedin vivotranscriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, themaiAgene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption ofmaiAresulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of β-glucans within the cell wall. themaiA-1mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking theA. fumigatus maiAgene to fungal cell wall homeostasis and virulence.
Recombinant biosensors for multiplex and super-resolution imaging of phosphoinositides
Authors: Maib Hannes , Adarska Petia , Hunton Robert , Vines James , Strutt David , Bottanelli Francesca , Murray David H.
Published: October 2023

Phosphoinositides are a small family of phospholipids, acting as signalling hubs and key regulators of cellular function. Detecting their subcellular distribution is crucial to gain insights into membrane organisation and is most commonly done by over-expression of biosensors. However, this leads to perturbations of phosphoinositide signalling and is challenging in systems that cannot be transfected. Here, we present a toolkit for the reliable, fast, multiplex, and super-resolution detection of all 8 phosphoinositides using a unifying staining approach for fixed cells and tissue, based on recombinant biosensors with self-labelling SNAP tags. These recombinant biosensors are highly specific, and reliably visualise the subcellular distributions of phosphoinositides across scales, ranging from 2D or 3D cell culture toDrosophilatissue. Using stimulated emission depletion (STED) microscopy, we reveal the nanoscale organisation of PI(3)P on endosomes and PI(4)P on the Golgi and confirm the preservation of subcellular membranes. Multiplex staining enables the investigation of phosphoinositide conversions and reveals an unexpected presence of residual PI(3,5)P2positive membranes in swollen lysosomes following PIKfyve inhibition. This approach enables the versatile, high-resolution visualisation of multiple phosphoinositide species in an unprecedented manner.
Adaptive capacity of a DNA polymerase clamp-loader ATPase complex
Authors: Subramanian Subu , Zhang Weilin , Nimkar Siddharth , Kamel Mazzin , O’Donnell Michael , Kuriyan John
Published: October 2023

The ability of mutations to facilitate adaptation is central to evolution. To understand how mutations can lead to functional adaptation in a complex molecular machine, we created a defective version of the T4 clamp-loader complex, which is essential for DNA replication. This variant, which is ∼5000-fold less active than the wildtype, was made by replacing the catalytic domains with those from another phage. A directed-evolution experiment revealed that multiple substitutions to a single negatively-charged residue in the chimeric clamp loader – Asp 86 – restore fitness to within ∼20-fold of wildtype. These mutations remove an adventitious electrostatic repulsive interaction between Asp 86 and the sliding clamp. Deep mutagenesis shows that the reduced fitness of the chimeric clamp loader is compensated for by lysine and arginine substitutions of several DNA-proximal residues in the clamp loader or the sliding clamp. Thus, the fitness decrease of the chimeric clamp loader is caused by a reduction in affinity between the clamp loader and the clamp. Our results demonstrate that there is a latent capacity for increasing affinity of the clamp loader for DNA and the sliding clamp, such that even single point mutations can readily compensate for the loss of function due to suboptimal interactions elsewhere.
Regulatory Mimicry of Cyclin-Dependent Kinases by Conserved Herpesvirus Protein Kinases
Authors: Koyanagi Naoto , Hengphasatporn Kowit , Kato Akihisa , Nobe Moeka , Takeshima Kosuke , Maruzuru Yuhei , Maenaka Katsumi , Shigeta Yasuteru , Kawaguchi Yasushi
Published: October 2023

Herpesviruses encode conserved protein kinases (CHPKs) that target cellular cyclin-dependent kinase (CDK) phosphorylation sites; thus, they are termed viral CDK-like kinases. Tyrosine 15 in the GxGxxG motifs of CDK1 and CDK2, whose phosphorylation down-regulates their catalytic activities, is conserved in the corresponding motifs of CHPKs. We found that herpes simplex virus 2 (HSV-2) CHPK UL13 mimicked the regulatory mechanism of CDKs. This regulatory mimicry was conserved in CHPKs encoded by herpesviruses subclassified into subfamilies other than HSV-2, suggesting CHPKs have regulatory and functional mimicry with CDKs. Phosphorylation of the corresponding Tyr in HSV-2 UL13 was required for the down-regulation of viral replication and pathogenicity, specifically in the central nervous system of mice, and for efficient viral recurrence in guinea pigs. These data highlight the dual impact of the regulatory mimicry of CDKs by CHPK on the fine-tuned regulation of lytic and latent HSV-2 infectionsin vivo.
Numerical investigation of particle effect on wear characteristic of centrifugal slurry pump based on CFD-DEM coupling
Authors: Shi Xiuwei , Ding Wujian , Xu Chunjie , Xie Fangwei , Tian Zuzhi
Published: October 2023

Purpose

In the process of conveying the solid–liquid two-phase medium of the centrifugal slurry pump, the wear of the flow-passing parts is an important problem affecting its life and safe operation. Therefore, a numerical investigation on the wear characteristics of the centrifugal slurry pump under different particle conditions was conducted.

Design/methodology/approach

A solid-liquid two-phase model based on CFD-DEM coupling is established and used to analyze the flow field and the wear characteristics of the flow-passing parts with different particle densities, volume fractions and sizes.

Findings

Particle conditions will affect the pump flow field. To analyze the pump wear characteristics, the wear distribution, wear value and cumulative force laws of flow-passing parts under different particle conditions are obtained. In each flow-passing part, with the increase of particle density, volume fraction and size, the wear area is concentrated and the wear depth increases. Under different particle conditions, the wear is mainly on the volute chamber and the blade pressure surface, and the tangential cumulative force of flow-passing parts is much larger than the normal cumulative force.

Originality/value

An accurate model and a coupled simulation method for predicting the wear of the slurry pump are obtained, and the wear characteristic law can provide a reference for the design of the slurry pump to reduce friction.
Method and finite element verification of indentation calculation for a novel air-spring mattress: for estimating spinal alignment in sleep postures
Authors: Chao Yao , Liu Tao , Shen Liming
Published: October 2023

Purpose

This study aimed to develop a method to calculate the mattress indentation for further estimating spinal alignment.

Design/methodology/approach

A universal indentation calculation model is derived based on the system theory, and the deformation characteristics of each component are analyzed by the finite element (FE) model of a partial air-spring mattress under the initial air pressure of 0.01–0.025 MPa. Finally, the calculation error of the model is verified.

Findings

The results indicate that the indentation calculation model could describe the stain of a mattress given the load and the constitutive model of each element. In addition, the FE model of a partial air-spring mattress can be used for further simulation analysis with an error of 1.47–3.42 mm. Furthermore, the deformation of the series system is mainly contributed by the air spring and the components directly in contact with it, while the top component is mainly deflection deformation. In addition, the error of the calculation model is 2.17–5.59 mm on the condition of 0.01–0.025 MPa, satisfying the engineering application. Finally, the supine spinal alignment is successfully extracted from the mattress indentation.

Research limitations/implications

The limitation of this study is that it needs to verify the practicality of the indentation calculation model for the Bonnier spiral spring mattress. The main feature of the Bonnier spring mattress is that all springs are connected, so the mattress deflection and neighborhood effect are more significant than those of the air-spring mattress. Therefore, the applicability of the model needs to be tested. Moreover, it is worth further research to reduce the deformation error of each component.

Practical implications

As part of the series of studies on the intelligent air-spring mattress, the indentation-based evaluation method of spinal alignment in sleep postures will be studied for hardness and intelligent regulation based on this study.

Social implications

The results of this research are ultimately used for the intelligent adjustment of air-spring mattresses, which automatically adjusts the hardness according to the user's sleep postures and spinal alignment, thus maintaining optimal spinal biomechanics. The successful application of this result could improve the sleep health of the general public.

Originality/value

Based on the series system theory, an indentation calculation model for mattresses with arbitrary structure is proposed, overcoming the dependence of parameters on materials and their combinations when fitting the Burgers model. Further, the spinal alignment in supine posture is extracted from the indentation, laying a theoretical foundation for further recognition and adjustment of the spinal alignment of the intelligent mattress.
Improving social interaction of the visually impaired individuals through conversational assistive technology
Authors: Ghafoor Komal , Ahmad Tauqir , Aslam Muhammad , Wahla Samyan
Published: October 2023

Purpose

Assistive technology has been developed to assist the visually impaired individuals in their social interactions. Specifically designed to enhance communication skills, facilitate social engagement and improve the overall quality of life, conversational assistive technologies include speech recognition APIs, text-to-speech APIs and various communication tools that are real. Enable real-time interaction. Using natural language processing (NLP) and machine learning algorithms, the technology analyzes spoken language and provides appropriate responses, offering an immersive experience through voice commands, audio feedback and vibration alerts.

Design/methodology/approach

These technologies have demonstrated their ability to promote self-confidence and self-reliance in visually impaired individuals during social interactions. Moreover, they promise to improve social competence and foster better relationships. In short, assistive technology in conversation stands as a promising tool that empowers the visually impaired individuals, elevating the quality of their social engagement.

Findings

The main benefit of assistive communication technology is that it will help visually impaired people overcome communication barriers in social contexts. This technology helps them communicate effectively with acquaintances, family, co-workers and even strangers in public places. By enabling smoother and more natural communication, it works to reduce feelings of isolation and increase overall quality of life.

Originality/value

Research findings include successful activity recognition, aligning with activities on which the VGG-16 model was trained, such as hugging, shaking hands, talking, walking, waving and more. The originality of this study lies in its approach to address the challenges faced by the visually impaired individuals in their social interactions through modern technology. Research adds to the body of knowledge in the area of assistive technologies, which contribute to the empowerment and social inclusion of the visually impaired individuals.
Determinants of effective Shariah compliance auditing in Palestine: a theoretical and conceptual analysis
Authors: Faza' Mustafa , Badwan Nemer , Hamdan Montaser
Published: October 2023

Purpose

This study aims to conduct a review and analysis of the literature on Shariah audit compliance by examining the difference between internal and external auditors, the scope of internal Shariah audits and the qualification of Shariah auditors.

Design/methodology/approach

The current study used content analysis and the descriptive approach to achieve the main objective of the study. To ensure that Islamic Financial Institutions’ (IFIs) practices preserve Shariah principles and values when providing Shariah-compliant products and services, this audit will be used to supervise and monitor the operations of IFIs. The main goal of Shariah compliance auditing is to protect the interests of IFIs stakeholders, including account holders, shareholders, creditors, management and employees, as well as the general public while ensuring that the mechanisms of checks and balances in place are appropriate and tailored to the goals and missions of its establishment following the Maqasid Al-Shariah.

Findings

The findings of this study attempt to contribute to the body of knowledge surrounding Shariah audit compliance by advising IFIs on the value of Shariah compliance auditing in addressing the needs of its stakeholders. As a result, the benefits of Shariah compliance audits will be maximized, and future legislative changes will be implemented to reduce or completely remove the risk of Shariah’s failure to comply.

Practical implications

This research advises IFIs on the usefulness of Shariah compliance auditing in addressing the demands of its stakeholders to add to the body of knowledge on Shariah audit compliance. Moreover, all parties involved to take action to reduce the gap that will significantly affect stakeholders’ confidence, particularly concerning the Shariah compliance of the IFIs’ products and services on their operations and activities.

Originality/value

The advantages of Shariah compliance audits will thus be maximized, and future regulatory improvements will be made to lessen or eliminate the danger of Shariah noncompliance.
Esports, video gaming and their fuzziness: a conceptualization and categorization
Authors: de Zoeten Max , Könecke Thomas
Published: October 2023

Purpose

The social and economic importance esports has gained over the past decades has led to a quickly evolving academic interest in the topic. Yet, current perspectives on esports frequently are not precise enough, too context-specific and/or focus on the question whether esports is sports or not. This means that no precise structural concept has been provided thus far. Such a conceptualization as well as a categorization of esports and related types of video gaming are provided in this paper.

Design/methodology/approach

This paper is based on a narrative review considering academic literature from 2000 to 2021 and publications of relevant esports organizations. The review is conceptually extended by structural parallels to traditional sports.

Findings

The central outcome of this research is conceptualizing esports as a victory-driven, organized performance comparison of exclusively human players playing video games in a competitive setting. This comparison is based solely on the performance achieved during a defined time frame according to fixed rules with comparably equal team (starting) conditions. This conceptualization is embedded in a general categorization of video gaming based on structural similarities with and differences to esports. Moreover, characteristics that were rejected in regards to the conceptualization and the categorization are discussed.

Originality/value

This paper provides a comprehensive categorization of esports and other types of video gaming based on structural similarities and differences. It is thus of high relevance for academia and sport management practice alike and can further the development in both fields.