bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of arterial inflammation as assessed by 18FDG-PET/CT and chemotherapy, in patients with lymphoma
Authors: Solomou E , Ioakimidis N , Terentes-Printzios D , Koutagiar I , Kafouris P , Pouli A , Sioni A , Giannouli S , Gardikioti V , Metaxas M , Kalikakis G , Tousoulis D , Tsioufis K , Anagnostopoulos C , Vlachopoulos C ,   ARTERY team
Published: October 2021

Abstract

Introduction
Inflammation plays a pivotal role in the pathogenesis of both Hodgkin and non-Hodgkin's lymphoma and it has been shown recently that disease burden is associated with arterial inflammation. This can be captured by 18F-fluorodeoxyglucose (18F-FDG) positron emission computed tomography (PET/CT), a commonly used imaging modality for staging and treatment response of patients with lymphoma, which has also been established as a reliable marker of arterial inflammation. Chemotherapy remains the cornerstone of lymphoma treatment; however, its direct effect on arterial 18F-FDG uptake is unknown.

Purpose
To investigate the effect of chemotherapy on arterial inflammation using 18F-FDG PET/CT imaging, in patients with lymphoma.

Methods
Sixty-six patients (22 male, mean age 56 years) with Hodgkin (n=34) or non-Hodgkin's lymphoma (n=32) underwent 18F-FDG PET/CT imaging at baseline, during and after completion of chemotherapy as part of their routine protocol. Arterial 18F-FDG uptake was assessed at the same time points by measuring the metabolic activity (maximum standardized uptake value (SUVmax) and the arterial target to background ratio (TBR)) of the aortic wall along the entire aorta. Patients with Hodgkin lymphoma underwent therapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim scan was performed at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non-Hodgkin's lymphoma underwent therapy with cyclophosphamide, doxorubicin, vincristine and prednisone+rituximab (R-CHOP). Their interim scan was obtained at 2 weeks post the 4th chemotherapy cycle. All patients were re-assessed with 18F-FDG PET/CT imaging 6–8 weeks after chemotherapy completion.

Results
Baseline total aortic TBR was not associated with the presence of diabetes, dyslipidaemia or smoking (p=0.258, p=0.302 and p=0.452, respectively). Twelve patients were receiving statin therapy, however, there was no significant difference in baseline aortic TBR between patients on statins and patients who were not on statin therapy (p=0.265). In the whole study sample, the index vessel TBR progressively decreased by 0.17 from baseline to 6 weeks following the end of treatment (p=0.013 ANOVA with Bonferroni Correction, Figure 1).

Conclusion
Our findings suggest that arterial inflammation is reduced during and post chemotherapy in patients with lymphoma. In addition, they indicate a potential role of molecular imaging in cardio-oncology, providing a longitudinal evaluation of disease severity and its consequences to the arterial wall metabolic activity with a single examination.

Funding Acknowledgement
Type of funding sources: None.
Uptake of [68Ga]-NODAGA-E[(cRGDyK)]2 is related to improvement in pump function in rats with chronic ischemic cardiomyopathy treated with cell therapy
Authors: Follin B , Hoeeg C , Nielsen C H , Hunter I , Bentsen S , Jensen J K , Binderup T , Ekblond A , Ripa R S , Kastrup J , Kjaer A 
Published: October 2021

Abstract

Background
An increasing number of patients living with chronic ischemic cardiomyopathy (ICM) are potential candidates for cell therapy, including adipose tissue-derived mesenchymal stromal cells (ASC). However, proper assessment of clinical effects in relation to cellular effector mechanisms, such as angiogenesis, is currently lacking.

Purpose
To investigate the prognostic value of assessing angiogenesis non-invasively using novel PET imaging in terms of functional outcome after cell therapy in a homologous animal model of ICM.

Methods
Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery. Four weeks after infarction, the rats were scanned with [18F]-FDG and echocardiography, and based on left ventricular ejection fraction (LVEF) and infarct size randomized to allogeneic ASC treatment (n=14) or saline (n=9). Animals were treated using echo-guided trans-thoracic intramyocardial injections. Follow-up echocardiography was performed four weeks after treatment. Angiogenesis was assessed non-invasively using the [68Ga]-NODAGA-E[(cRGDyK)]2 (RGD) PET-tracer before treatment and two weeks after the treatment (Figure). The output was RGD-uptake by maximum standardized uptake value (SUVmax).

Results
RGD-uptake in the infarct area significantly decreased in the saline group (p=0.04), while this decline was not significant in the ASC group (p=0.58). There was no effect on LVEF of the cell therapy in this study (p=0.70). When the rats were grouped by RGD-uptake post treatment, the high RGD-uptake group (n=8) improved LVEF compared to the rats with medium or low RGD-uptake (n=15, p=0.04) irrespective of the treatment. This could indicate that non-invasive detection of a high degree of myocardial angiogenesis measured using RGD is predictive of improvement in cardiac pump function in ICM.

Conclusions
Following injection of ASC or saline, a high RGD-uptake precluded improvement in pump function. This is the first evidence of how uptake of the novel RGD tracer relates to changes in pump function in ICM and the results could affect the design of future clinical trials using regenerative therapy for ICM patients.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Aase and Ejnar Danielsens FondDoctor Sofus Carl Emil Friis and wife Olga Doris Friis' Scholarship Study design, RGD-uptake, and results
Patients with rare autoimmune inflammatory disorders demonstrate sub-clinical left ventricular dysfunction
Authors: Khanna S , Wen I , Gupta A , Thakur A , Bhat A , Chen H H L , Gan G C H , Tan T C 
Published: October 2021

Abstract

Background
ANCA-associated Vasculitis (AAV) and inflammatory myositis (IM) are rare inflammatory autoimmune disorders mediated via pro-inflammatory cytokines and result in a systemic inflammatory state with multi-organ involvement. There is growing evidence to suggest cardiovascular involvement within these inflammatory states. Left ventricular global longitudinal strain (LV-GLS) is proposed to be a more sensitive measure of LV systolic function when compared to standard two-dimensional measures such as LV ejection fraction (LVEF).

Purpose
The purpose of this study was to assess for subclinical cardiac dysfunction in these cohorts when compared to controls.

Methods
Consecutive patients with AAV (n=56) and IM (n=68) admitted to our institution during 2013–2021 were assessed. Patients with pre-existing cardiovascular disease, significant renal impairment (eGFR &lt;30mL/min/1.73m2), LVEF &lt;50% or lack of comprehensive transthoracic echocardiography during admission were excluded (n=72). LV-GLS was measured offline using vendor-independent software (TomTec Arena, Germany v4.6).

Results
A total of 52 patients (22 AAV and 30 IM) were age- and gender-matched to 52 controls. In comparison of the two study populations (AAV and IM), patients with AAV had higher rates of renal impairment (p=0.02) but lower rates of interstitial lung disease when compared to IM (p=0.02). There were no differences between the two groups in terms of cardiovascular risk factors, demographics or other laboratory investigations (p&gt;0.05 for all). In comparison to the control population, patients with AAV and IM had higher indexed LV mass and a lower TAPSE, respectively, when compared to controls. These cohorts also demonstrated impaired LV-GLS (−17.7±2.6 vs −20.6±2.4; p&lt;0.01) when compared to healthy controls, despite no differences in LVEF (62.6±7.8 vs 61.8±5.4; p=0.56) between both groups.

Conclusions
Our results suggest that patients with autoimmune inflammatory disorders demonstrate subclinical LV dysfunction which is likely secondary to a chronic inflammatory state.

Funding Acknowledgement
Type of funding sources: None.
Dapagliflozin decreases atherosclerotic plaque instability via regulating macrophage pyroptosis
Authors: Xu L , Dai Y , Yao K , Yang H , Sun A , Qian J , Ge J 
Published: October 2021

Abstract

Background
Vulnerable plaques are characterized by infiltration of inflammatory cells, playing a key role in the progression of acute coronary events. It's important to clarify the inflammatory mechanism of unstable plaque formation. Several clinical trials have demonstrated that dapagliflozin could reduce major adverse cardiac events in whether diabetic or non-diabetic patients. However, the underlying cardioprotective mechanism of dapagliflozin remains unclear. This study was aimed to investigate the role of dapagliflozin in regulating macrophage pyroptosis and vulnerable plaque formation.

Methods
20 ApoE−/− mice (control) were fed with high fat diet while another 20 ApoE−/− mice were challenged with high fat diet plus dapagliflozin for 12 weeks. The extent and instability of atherosclerotic plaque was determined by oil-red staining, HE staining, immunofluorescence staining and electron microscopy. Changes in subsets of immune cells were evaluated by flow cytometry. Plasma cytokines were assessed by ELISA. Microarray analysis was applied to detect gene expressions while Western blot and real-time PCR was used to assess gene expression levels.

Results
Morphology studies revealed that dapagliflozin could inhibit plaque formation and reduce instability in ApoE−/− mice. FACS data showed that dapagliflozin could decrease CD11b+Ly6Chigh M1 macrophages differentiation and inhibit foam cells formation in ApoE−/− mice. Microarray analysis and in vitro studies exhibited that dapagliflozin could induce the down regulation of NLRP3, caspase-1, IL-1β, IL-18 and MMP-7/10/12/14 to retard macrophage pyroptosis and foam cell formation.

Conclusions
We have characterized a novel role for dapagliflozin in modulating atherosclerotic lesion development and progression. We envision that this study may provide several potential therapeutic targets for treatment of acute coronary syndromes.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Shanghai Sailing Program
Deficiency of myeloid prolyl hydroxylase domain proteins aggravates atherogenesis via macrophage apoptosis and paracrine fibrotic signaling
Authors: Sluimer J , Van Kuijk K , Demandt J A F , Perales-Paton J , Kuppe C , Jin H , Matic L , Mees B , Hedin U , Biessen E A L , Carmeliet P , Baker A H , Kramann R K , Schurgers L J , Saez-Rodriguez J 
Published: October 2021

Abstract

Background
Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing macrophage function in plaque hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs in atherosclerosis.

Methods
Myeloid specific PHD knockout (PHDko) mice were fed high cholesterol diet for 6–12 weeks to induce atherosclerosis. Plaque parameters, e.g. plaque size and macrophage content, were analyzed. Bulk and single cell RNA sequencing was performed on PHD2 BMDMs and plaque macrophages, respectively.

Results
Aortic root plaque size was augmented 2.6fold in PHD2cko, and 1.4-fold in PHD3ko, but not in PHD1ko mice compared to controls. Macrophage apoptosis was promoted in PHD2cko and PHD3ko mice in vitro and in vivo, via the HIF1α/BNIP3 axis. Bulk and single cell RNA data of PHD2cko bone-marrow-derived macrophages (BMDM) and plaque macrophages, respectively, confirmed these findings and were validated by siRNA silencing. Human plaque BNIP3 mRNA associated with plaque necrotic core, suggesting similar adverse effects. Further, PHD2cko plaques displayed enhanced fibrosis, independent of macrophage MMP activity, collagen secretion or proliferation and of SMC collagen production, or proliferation. Rather, PHD2cko BMDMs enhanced fibroblast collagen secretion in a paracrine manner. Nichenet in silico analysis of macrophage-fibroblast communication predicted SPP1 signaling as regulator, in line with enhanced plaque SPP1 protein content, and SPP1 mRNA in TREM2-foamy plaque macrophages, but not in neutrophils.

Conclusion
Myeloid PHD2cko and PHD3ko enhanced plaque growth, macrophage apoptosis, and PHD2cko activated paracrine collagen secretion by fibroblasts.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO, Leducq
Endothelial progenitor cells modulate the phenotype of smooth muscle cells and increase their neointimal accumulation following vascular injury
Authors: Mause S , Ritzel E , Deck A , Vogt F , Liehn E 
Published: October 2021

Abstract

Background
Smooth muscle cells (SMCs) are the main driver of neointima formation and restenosis following vascular injury. In animal models, endothelial progenitor cells (EPCs) accelerate endothelial regeneration and reduce neointima formation after arterial injury, however EPC-capture stents do not to reduce target vessel failure compared to conventional stents. Here we examined the influence of EPCs on features of SMCs pivotal for their impact on neointima formation including proliferation, migration and phenotype switch.

Methods and results
EPCs, their conditioned medium and EPC-derived microparticles induced proliferation of SMCs while limiting their apoptosis. In transwell membrane experiments and scratch assays EPCs stimulated migration of SMCs and accelerated their recovery from scratch-induced injury. Treatment of SMCs with EPC-derived conditioned medium or microparticles triggered transformation of SMCs towards a synthetic phenotype. However, co-cultivation of EPCs and SMCs enabling direct cell-cell contacts preserved their original phenotype and protected from the transformative effect of SMC cholesterol-loading. Adhesion of EPCs to SMCs was stimulated by SMC injury and reduced by blocking CXCR2 and CCR5. Interaction of EPCs with SMCs modulated their secretome and synergistically increased the release of selected chemokines. Following carotid wire injury in athymic mice, injection of EPCs resulted not only in reduced neointima formation but also in altered cellular composition of the neointima with augmented accumulation of SMCs.

Conclusion
EPCs stimulate proliferation and migration of SMCs and increase their neointimal accumulation following vascular injury. Furthermore, EPCs modify the SMC phenotype with protection from the transformative effect of cholesterol when direct cell-cell contact is established.

Funding Acknowledgement
Type of funding sources: None.
Infrared study and computational simulations of coronary arteries atherosclerotic lesions for early diagnosis of disease progression
Authors: Mamarelis I , Mamareli C H R , Mylonas E , Mamareli V , Spilopoulos K , Kotoulas S , Kolovou P , Subramaniyan P , Muthukumaran P , Badilescu S , Koui M , Theophanides T , Kotoulas C H R , Anastassopoulou J 
Published: October 2021

Abstract

Introduction
Coronary artery atherosclerotic disease is the most common cardiovascular disease and bypass grafting surgery (CABG) is an effective treatment. However, the pathogenic mechanism of coronary arteries atherosclerosis and disease progression is not yet clear.

Purpose
The use of FT-IR spectroscopy, hyperspectral microscope and mathematical simulation models are some of the tools to predict the morphological and elasticity disorders in the vessel wall due to molecular structure changes.

Methods
Biopsies of atherosclerotic native coronary arteries from 54 patients (44–85 years), who underwent coronary endarterectomy during bypass grafting surgery (CABG), were examined ex vivo. The FT-IR-spectra were recorded with a Nicolet-6700 spectrometer. Morphological changes of atheromatic plaques were performed with SEM-EDX, Fei-Co. CytoVita-Olympus hyperspectral microscope was used to obtain the cells.

Results
FT-IR spectroscopy (Figure 1A) showed that the disease affects the protein folding, leading to amyloid formation (beta-sheets), lipid peroxidation and AGEs (Advanced Glycation end products) production. The detection of amorphous CaCO3 (1415 and 872 cm–1) deposits in high lipophilic regions was of high importance. Increased mineral concentration leads to increased formation of crystalline deposits, consisting of CaCO3, CaHPO4, Ca3(PO4)2 and inorganic hydroxyapatite, resulting in arterial stenosis. Hyperspectral images confirmed the formation of micelles (1) due to amyloidosis and calcified cells (2), in agreement with FT-IR, ImageJ analysis data. Mathematical simulation model based on finite element method (Figure 1E) showed that arterial wall damage and elasticity changes were not homogenous. This model provides the time of crystallization of the calcium salts, which play crucial role to stenosis.

Conclusions
FT-IR spectra showed that the formation of amorphous CaCO3 in the presence of Mg2+, in reach of oxidized lipids regions, inhibit the development of coronary artery stenosis. Excessive of Ca2+ efflux promotes the crystallinity of CaCO3 and Ca3(PO4)2 deposits, leading to the development of atherosclerotic plaques and coronary artery stenosis. Mathematical models approach in a much better way the progression of arterial atherosclerosis.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Integrative single cell RNA-sequencing descrambles a substantial divergence of adaptive immune cell identities and transcriptional programs in mouse and human atherosclerosis
Authors: Horstmann H , Anto Michel N , Sheng X S , Hansen S , Lindau A , Klymiuk I , Marchini T , Winkels H , Verheyen N , Gerhardt T , Oswald W , Conhert T , Bode C , Zirlik A , Wolf D ,   Vascular Immunology lab
Published: October 2021

Abstract

Aims
The distinct function of immune cells in human atherosclerosis has been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches.

Methods and results
We performed single cell RNA-sequencing (scRNAseq) to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire was dominated by T cells with a considerable inter-patient variability and an unexpected heterogeneity. We performed bioinformatical integration with 7 mouse data sets and discovered a total of 38 cellular identities, of which some were not conserved between species and exclusively found in mice or humans. Locations, frequencies, and transcriptional programs of immune cells in preclinical mouse models did not resemble the immune cell landscape in human atherosclerosis. In contrast to mice, human plaques were not myeloid- and B cell-dominated and instead contained several T cell phenotypes with hallmarks of T cell memory, dysregulation, exhaustion, and activation. Human immune cells were predominantly enriched for transcriptional programs of hypoxia, glucose, and autoimmunity. In a validation cohort of 43 patients activated immune cell subsets defined by multi-colour flow cytometry associated with cerebral ischemia and coronary artery disease.

Conclusion
Here, we uncover yet undefined immune cell types associating with clinical disease. This leukocyte atlas of human atherosclerosis builds the conceptual basis for subsequent identification of cellular targets for clinical immunomodulatory therapies and risk prediction.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ERC Starting Grant
High-density lipoprotein lipid peroxidation in association with presence of coronary artery disease and atrial fibrillation in a large cross-sectional study
Authors: Pagonas N , Sasko B , Mueller R , Jaensch M , Dammermann W , Hillmeister P , Buschmann I , Ritter O , Westhoff T H , Kelesidis T 
Published: October 2021

Abstract

Background
The function of high-density lipoprotein (HDL) cholesterol may play a more important role in the prevention of cardiovascular disease compared to the concentration of the HDL. Cardiovascular diseases such as coronary artery disease (CAD) and atrial fibrillation (AF) have been linked to impaired HDL function.

Purpose
The aim of the present study is to assess a biochemical measure of the antioxidant function of HDL and its association with presence of CAD and AF.

Methods
Patients admitted for elective cardiac catheterization were recruited in this cross-sectional study. Out of 1231 participants that were included in the analyses, 727 patients had confirmed CAD (CAD group), 369 patients had no CAD (no CAD group) and 129 persons were included as a control group. HDL function was measured in sera by determination of HDL-lipid peroxidation content (HDLox) assessed by a validated fluorometric cell-free biochemical assay and was normalized for the levels of HDL cholesterol (normalized HDLox/HDL-C ratio or nHDLox; no units). Results are expressed as median with interquartile range. Associations of nHDLox with presence of CAD and AF were assessed by univariate and multivariate analyses.

Results
Participants in the CAD group had higher levels of nHDLox (0.80, 0.61–1.03) compared to the no CAD (0.70, 0.55–0.93) and control (0.66, 0.55–1.03, no units, p&lt;0.001) group. Out of 1206 participants, 233 (19%) had AF and 973 (81%) had no AF. Patients with AF have also higher nHDLox (0.82, 0.60–10.03) compared to persons without AF (0.73, 0.58–0.98, p=0.03). In univariate analysis nHDLox was associated with CAD (p&lt;0.001). In multivariate analysis adjusted for age, gender, CAD, BMI and hypertension, nHDLox was a strong independent predictor of atrial fibrillation (p=0.015) but was not an independent predictor of CAD (p&gt;0.05)

Conclusions
Reduced antioxidant function of HDL (increased HDLox measured by a biochemical assay), a metric of HDL function, is increased in patients with atherosclerosis and manifested CAD and is also associated with the presence of atrial fibrillation independent of the presence of CAD.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Medical School of Brandenburg-MHB Fontane
Diploid genome assembly of Kluyveromyces marxianus NRRL Y-50883 (SLP1)
Authors: Gómez-Márquez Carolina , Sandoval-Nuñez Dania , Gschaedler Anne , Romero-Gutiérrez Teresa , Amaya-Delgado Lorena , Morales J Alejandro 
Published: October 2021

Abstract
The yeast Kluyveromyces marxianus SLP1 has the potential for application in biotechnological processes because it can metabolize several sugars and produce high-value metabolites. K. marxianus SLP1 is a thermotolerant yeast isolated from the mezcal process, and it is tolerant to several cell growth inhibitors such as saponins, furan aldehydes, weak acids, and phenolics compounds. The genomic differences between dairy and nondairy strains related to K. marxianus variability are a focus of research attention, particularly the pathways leading this species toward polyploidy. We report the diploid genome assembly of K. marxianus SLP1 nonlactide strain into 32 contigs to reach a size of ∼12 Mb (N50 = 1.3 Mb) and a ∼39% GC content. Genome size is consistent with the k-mer frequency results. Genome annotation by Funannotate estimated 5000 genes in haplotype A and 4910 in haplotype B. The enriched annotated genes by ontology show differences between alleles in biological processes and cellular component. The analysis of variants related to DMKU3 and between haplotypes shows changes in LAC12 and INU1, which we hypothesize can impact carbon source performance. This report presents the first polyploid K. marxianus strain recovered from nonlactic fermenting medium.