bluuebunny/crossref_metadata_2025_split huggingface dataset:
APAC treatment limits collar-induced carotid atherosclerotic plaque development in apoE-/- mice
Authors: Bot I , Delfos L , Hemme E , Kovanen PT , Jouppila A , Lassila R 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation
Introduction and aim: Mimics of mast cell-derived heparin proteoglycans (HEP-PG) can be tailored to molecules carrying both antiplatelet and anticoagulant properties. These dual antiplatelet and anticoagulant (APAC) constructs can also shield adhesion molecules such as P-selectin and VCAM-1 expressed by endothelial cells upon atherosclerosis development. We hypothesize that via this way, APAC prevents macrophage accumulation and lesion development. In this study, we therefore determined the efficacy of APAC in inhibiting atherosclerosis.

Methods
Male western-type diet fed apoE-/- mice were equipped with perivascular carotid artery collars to induce atherosclerosis. In this collar model, mRNA expression of adhesion molecules such as ICAM-1, VCAM-1, P-Selectin but also of Platelet Factor 4 (PF4) are significantly upregulated upon lesion development (all P&lt;0.05 at 2 weeks after collar placement compared with control arteries). From lesion initiation, mice were treated with 0.2 mg/kg APAC or vehicle control (i.v, 3x per week, n=12-14 per group) for 2.5 weeks. At 5 weeks after collar placement, mice were sacrificed.

Results
APAC treatment did not affect body weight or plasma total cholesterol levels of the mice during the experiment. Interestingly, carotid artery plaque size was reduced by over 50% upon APAC treatment (APAC: 50±10*10E3 versus controls: 102±13*10E3 square µm; P&lt;0.01). This observation was aligned with reduced plaque macrophage area (APAC: 20±5*10E3 versus controls: 33±5*10E3 square µm) and collagen content (APAC: 13±4*10E3 versus controls: 28±6*10E3 square µm; P&lt;0.05).

Conclusion
We here show that APAC effectively inhibits atherosclerotic lesion development when administered during lesion initiation and may have potential as therapeutic agent to prevent atherosclerosis.
White matter penetrating arteriole dysfunction correlates with MRI-defined white matter integrity in patients with Alzheimer's disease
Authors: Bagi ZSOLT , Kroenke C , Keene CD , Sherman LS , Back SA 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): National Institute of Health

Objectives
Patients with Alzheimer’s Disease (AD) display cerebral white matter (WM) hyperintensities in association with microvascular brain injury (mVBI) and cerebral microinfarcts. We determined the extent to which vasomotor dysfunction of WM penetrating arterioles is associated with mVBI in autopsy brains from patients with low or high AD neuropathology, and determined if these changes correlate with quantitative indices of MRI-defined WM integrity.

Methods
We analyzed 28 consecutive cases of prefrontal rapid autopsies in a population-based cohort with low or high AD neuropathological changes, and with or without cerebral microinfarcts (mVBI). WM penetrating and pial surface arteriolar responses to the endothelium-dependent agonist, bradykinin were assessed ex vivo with videomicroscopy. Expression of vascular endothelial nitric oxide synthase (eNOS) and NAD(P)H-oxidase (Nox1,2 and 4 isoforms) was measured with quantitative PCR. Diffusion tensor imaging was used to measure mean apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in post-mortem prefrontal WM.

Results
Patients with high AD neuropathology and mVBI exhibited a significantly reduced dilation in response to bradykinin selectively in WM arterioles, when compared to low or high AD cases without mVBI or to pial surface arterioles. Expression of eNOS was reduced, whereas Nox-1 expression was increased in WM arterioles in AD and mVBI cases. Moreover, we found that in cases with low AD pathology the magnitude of bradykinin-induced WM arteriole dilation was correlated with higher FA and lower ADC. In contrast, dilation to bradykinin was associated with lower FA and higher ADC in cases with high AD neuropathology.
Interpretation: Selectively impaired vasodilation to the endothelium-dependent agonist, bradykinin occurs in WM penetrating arterioles in AD patients with WM microinfarcts, which is likely due to reduced nitric oxide and an increase in Nox1-derived reactive oxygen species production. Notably, the bradykinin response of WM arterioles strongly correlated with MRI-defined WM integrity suggesting that impaired bradykinin-mediated vasodilation in WM penetrating arterioles contributes to disrupted white matter microstructural integrity as defined by MRI.
Analysis of miRNA profile in circulating extracellular vesicles of patients with pulmonary arterial hypertension
Authors: Khandagale A , Corcoran P , Nikpour M , Siegbahn A , Christersson C 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): Swedish Research Council

Introduction
Pulmonary arterial hypertension (PAH) is characterized by a progressive elevation of pulmonary pressure leading to right ventricular dysfunction and is associated with a poor prognosis. Patients with PAH have increased numbers of circulating extracellular vesicles (EVs), which are small membrane vesicles (&lt;1 µm) released from different cells. EVs contain surface antigens, proteins and genetic material, and serve as vectors of intercellular communication. MicroRNAs (miRs) are small RNAs that act as post-transcriptional regulators inhibiting gene expression. Alteration of miR expression is associated with stage, progression and severity of different diseases making them suitable as potential biomarker. The aim of the study was to evaluate the miRNA profile contained in EVs derived from plasma of both control healthy subjects and patients with PAH.

Methods
Circulating EVs, purified from platelet free plasma, from 9 healthy controls (HC) and 10 PAH patients were analyzed. After total RNA isolation, fixed volumes of total RNA were biotinylated to generate fragmented cRNA. Samples were then subjected to Microarray analysis using GeneChip miRNA 4.0 Array. Data was further analysed using various bioinformatics tools.

Results
Total of 762 miRs were identified while comparing PAH vs HC groups, of which 22 were found to be down-regulated and 3 were up-regulated in PAH group (Table 1). Gene ontology enrichment analysis revealed various cell signaling pathways where-in identified miRs are involved.

Conclusions
PAH patients pack and transport a differentiated expression profile of miRs, suggesting that EVs might serve as signaling vectors. Further analyses of the functionality of EVs' miRs is currently undergoing in our lab to understand its role during PAH progression and/or inhibition.
Influence of factors on systolic blood pressure in patients with hypertension identified during screening
Authors: Bekbergenova ZH , Derbissalina G , Umbetzhanova A , Batarbekova SH , Masharipova A , Mauletbayeva G , Akhmetova D , Kelimberdiyeva E 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: None. Main funding source(s): -
Background / Introduction. Hypertension is one of the most common causes of myocardial infarction and stroke in the Republic of Kazakhstan (RK). Blood pressure (BP) is an easily measured indicator of hypertension.

Purpose
To assess the effect of various factors on systolic blood pressure (SBP) in patients with hypertension identified at screening.

Methods
A survey of 354 patients with hypertension identified at screening was carried out and the influence of various factors on SBP was assessed.

Results
The average age of patients is 54 years [Q1-Q3: 50-54], of which 36.2% are men, 63.8% are women. Middle systolic blood pressure is 140 [Q1-Q3: 130-140] mm Hg. Most of the respondents have varying degrees of obesity. The average body mass index is 31.86 [Q1-Q3: 29.4-31.86]. The average waist is 95 [Q1-Q3: 92-95]. Mean values of total cholesterol. 5.8 [Q1-Q3: 5.6-5.8].
With an increase in age by 1 full years, an increase in SBP by 0.148 mm.Hg. should be expected. In accordance with the coefficient of determination R2 in the resulting model, 0.56% of the factors influencing the value of SBP were taken into account.
With an increase in body mass index by 1, a decrease in SBP by 0.059 mm Hg should be expected. In accordance with the coefficient of determination R2 in the resulting model, 0.04% of the factors influencing the SBP were taken into account.
With an increase in the waist by 1 cm, an increase in SBP by 0.059 mm Hg should be expected. In accordance with the coefficient of determination R2 in the resulting model, 0.09% of the factors influencing the SBP were taken into account.
With an increase in total cholesterol by 1 mmol/l. an increase in SBP by 24.466 mm Hg should be expected. In accordance with the coefficient of determination R2, the resulting model took into account 34.27% of the factors affecting the SBP. The effect of total cholesterol on SBP was statistically significant (p = 0.001) (methods used: Kruskal-Wallis test).

Conclusion (s)
Thus, the effect of total cholesterol on SBP is statistically significant (p = 0.001). With an increase in total cholesterol by 1 mmol/l. an increase in SBP by 24.466 mm Hg should be expected.
A randomised trial on modulating endogenous fibrinolysis in patients with acute coronary syndrome VaLiDate-R
Authors: Gue Y X , Kanji R , Wellsted D , Srinivasan M , Wyatt S , Gorog D 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Private company. Main funding source(s): This study is funded by Bayer PLC, 400 South Oak Way, Green Park, Reading, Berkshire, RG2 6AD.

Background
Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals.

Methods and Results
The VaLiDate-R study is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time &gt;2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test.

Conclusion
If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.
Single cell profiling of adipose tissue in atherosclerosis
Authors: Thanigai Arasu U , Ord T , Liikkanen J , Kettunen S , Lonnberg T , Palani S , Yla-Herttuala S , Roivainen A , Kaikkonen MU 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Academy of Finland
Sigrid Jusélius Foundation
Adipose tissue influences the physiological and pathological processes in our body by regulating lipid storage and metabolic homeostasis. Extracellular matrix (ECM) is a dynamic and complex assemblage consisting of polysaccharides, proteogylcans and signalling proteins. Though both adipocytes and non- adipose cells of the stromal fraction contribute to ECM maintenance, role of adipose tissue ECM in the disease remains poorly characterised. High fat diet (HFD) and obesity represent major risk factors for atherosclerosis. Our overall aim in this study was to understand HFD induced changes in the adipose tissue during atherosclerosis progression using single cell RNA sequencing (scRNA-seq), to identify the ligands responsible for changes in the expression of ECM components and to characterise the role of ECM protein fibrillin in disease associated tissue changes.
We performed scRNA-seq in the adipose tissue of control mice and atherosclerotic LDLR-/- / ApoB100/100 subjected to 1 (early disease) or 3 months (advanced disease) of HFD. This allowed us to identify 13 different cell types in the adipose tissue of the diseased mice. Among them, we identified mesenchymal cells (MSC) undergoing changes from putatively adipogenic to fibrogenic cells. The differentially expressed genes in the MSC population exhibited functions related to ECM development, maintenance and signalling. We identified Fibrillin-1 (Fbn1) as one of the most prominent up regulated genes and studied the effect of Fbn1 knockout in ApoE-/- Fbn1C1039G+/- mice. The Fbn1 knockout mice model suited our experimental design to study the adipose tissue during atherosclerosis as the mice developed significantly large and unstable plaques characterised by large necrotic core. Our results demonstrated that adipose tissue expresses a new subtype with HFD in Fbn1 knockout mice, which could be associated with insulin resistance and fat accumulation. Fbn1 knockout led to an altered phenotype of MSCs (or adipocytes) in adipose tissue.
Altogether, our analysis provides the first steps toward understanding the role of MSCs in ECM-related changes during atherosclerosis and HFD stimulation.
Whole-genome sequencing analysis and protocol for RNA interference of the endoparasitoid waspAsobara japonica
Authors: Kamiyama Takumi , Shimada-Niwa Yuko , Tanaka Hiroyuki , Katayama Minami , Kuwabara Takayoshi , Mori Hitoha , Kunihisa Akari , Itoh Takehiko , Toyoda Atsushi , Niwa Ryusuke 
Published: June 2022

AbstractAsobara japonica is an endoparasitic wasp that parasitizes Drosophila flies. It synthesizes various toxic components in the venom gland and injects them into host larvae during oviposition. To identify and characterize these toxic components for enabling parasitism, we performed the whole-genome sequencing (WGS) and devised a protocol for RNA interference (RNAi) with A. japonica. Because it has a parthenogenetic lineage due to Wolbachia infection, we generated a clonal strain from a single wasp to obtain highly homogenous genomic DNA. The WGS analysis revealed that the estimated genome size was 322 Mb with a heterozygosity of 0.132%. We also performed RNA-seq analyses for gene annotation. Based on the qualified WGS platform, we cloned ebony-Aj, which encodes the enzyme N-β-alanyl dopamine synthetase, which is involved in melanin production. The microinjection of double-stranded RNA (dsRNA) targeting ebony-Aj led to body colour changes in adult wasps, phenocopying ebony-Dm mutants. Furthermore, we identified putative venom genes as a target of RNAi, confirming that dsRNA injection-based RNAi specifically suppressed the expression of the target gene in wasp adults. Taken together, our results provide a powerful genetic toolkit for studying the molecular mechanisms of parasitism.
COVID-19 infection complicated with acute pulmonary embolism treated with percutaneous pulmonary artery thrombectomy: a case report
Authors: Petrov Ivo , Stankov Zoran , Dobrev Georgi , Polomski Petar 
Published: June 2022

Abstract

Background
Coronavirus disease 2019 (COVID-19) disease is a highly prothrombotic state. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are observed with increased incidence in patients infected with the severe acute respiratory syndrome coronavirus 2 virus.

Case summary
A 57-year-old male patient with a recent COVID-19 infection complained of leg swelling shortly after his COVID ward discharge. A few days later he was hospitalized with acute massive PE and DVT of his left leg was diagnosed. In another facility, as the first line of treatment, the PE was managed with catheter-directed therapy (CDT) using thrombus defragmentation via 5F (French) Pigtail catheter and supraselective application of 40 mg alteplase. Following the procedure, in addition, 50 mg alteplase was also applied as a 1 hour systemic infusion. Despite the haemodynamic stabilization of the patient, he remained persistently symptomatic and tachycardic. Three days later—in our institution, a second computed tomography pulmoangiography revealed massive thrombotic masses mainly in the left pulmonary artery. Successful percutaneous thrombus aspiration was conducted. The procedure was uneventful with an immediate drop of systolic pulmonary artery pressure from 68 to 47 mmHg and relief of the patient’s symptoms.

Discussion
In the era of the COVID-19 pandemic, physicians have to remain vigilant of its potential thrombotic complications, the most commonly observed being DVT and PE. We demonstrated the efficacy of percutaneous thrombus aspiration in a patient with acute COVID-19-associated PE, after initial CDT with thrombus defragmentation and high-dose tissue plasminogen activator was implemented with a suboptimal result.
Lipid A heterogeneity and its role in the host interactions with pathogenic and commensal bacteria
Authors: Saha Sukumar , Pupo Elder , Zariri Afshin , van der Ley Peter 
Published: June 2022

AbstractLipopolysaccharide (LPS) is for most but not all Gram-negative bacteria an essential component of the outer leaflet of the outer membrane. LPS contributes to the integrity of the outer membrane, which acts as an effective permeability barrier to antimicrobial agents and protects against complement-mediated lysis. In commensal and pathogenic bacteria LPS interacts with pattern recognition receptors (e.g LBP, CD14, TLRs) of the innate immune system and thereby plays an important role in determining the immune response of the host. LPS molecules consist of a membrane-anchoring lipid A moiety and the surface-exposed core oligosaccharide and O-antigen polysaccharide. While the basic lipid A structure is conserved among different bacterial species, there is still a huge variation in its details, such as the number, position and chain length of the fatty acids and the decoration of the glucosamine disaccharide with phosphate, phosphoethanolamine or amino sugars. New evidence has emerged over the last few decades on how this lipid A heterogeneity confers distinct benefits to some bacteria because it allows them to modulate host responses in response to changing host environmental factors. Here we give an overview of what is known about the functional consequences of this lipid A structural heterogeneity. In addition, we also summarize new approaches for lipid A extraction, purification and analysis which have enabled analysis of its heterogeneity.
VviAGL11 self-regulates and targets hormone- and secondary metabolism-related genes during seed development
Authors: Amato Alessandra , Cardone Maria Francesca , Ocarez Nallatt , Alagna Fiammetta , Ruperti Benedetto , Fattorini Chiara , Velasco Riccardo , Mejía Nilo , Zenoni Sara , Bergamini Carlo 
Published: June 2022

AbstractVviAGL11, the Arabidopsis SEEDSTICK homolog, has been proposed to have a causative role in grapevine stenospermocarpy. An association between a mutation in the coding sequence (CDS) and the seedless phenotype was reported, however, no working mechanisms have been demonstrated yet. We performed a deep investigation of the full VviAGL11 gene sequence in a collection of grapevine varieties belonging to several seedlessness classes that revealed three different promoter-CDS combinations. By investigating the expression of the three VviAGL11 alleles, and by evaluating their ability to activate the promoter region, we observed that VviAGL11 self-activates in a specific promoter-CDS combination manner.Furthermore, by transcriptomic analyses on ovule and developing seeds in seeded and seedless varieties and co-expression approaches, candidate VviAGL11 targets were identified and further validated through luciferase assay and in situ hybridization. We demonstrated that VviAGL11 Wild Type CDS activates Methyl jasmonate esterase and Indole-3-acetate beta-glucosyltransferase, both involved in hormone signaling and Isoflavone reductase, involved in secondary metabolism. The dominant-negative effect of the mutated CDS was also functionally ectopically validated in target induction. VviAGL11 was shown to co-localize with its targets in the outer seed coat integument, supporting its direct involvement in seed development, possibly by orchestrating the crosstalk among MeJA, auxin, and isoflavonoids synthesis.In conclusion, the VviAGL11 expression level depends on the promoter-CDS allelic combination, and this will likely affect its ability to activate important triggers of the seed coat development. The dominant-negative effect of the mutated VviAGL11 CDS on the target genes activation was molecularly validated. A new regulatory mechanism correlating VviAGL11 haplotype assortment and seedlessness class in grapevine is proposed.
Narrating by Doing: A Bridging Concept for Understanding and Informing the Design of Tangible Interfaces for Storytelling
Authors: Sylla Cristina , Gil Maitê , Pereira Íris Susana Pires 
Published: June 2022

Abstract
We present and discuss the concept ‘narrating by doing’ as the process of creating narratives by performing different embodied actions with tangible interfaces for storytelling. We characterize it as a ‘bridging concept’ that can facilitate exchange between theory and design, informing research and design of TUIs for storytelling targeting young children. The concept builds on theories of cognition, learning and narration, specifically drawing upon the following perspectives: Constructionism, Socio-Constructivism, Embodied Cognition, Narratology and The Narrative Practice Hypothesis. Building upon these theoretical foundations, we identify and discuss four ‘design articulations’ (i.e. important parameters that express the qualities of the concept), namely communicative situation, narrative function of the tangible objects, collaborative and embodied actions and the narrator’s position. Finally, we add evidence to the concept and discuss its productiveness by presenting a set of considerations to inform the design of tangible interfaces for storytelling.