bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association postprandial hypertriglyceridemia, levels of leptin and carotid intima-media thickness in patients with coronary artery disease combined with nonalcoholic liver steatosis
Authors: Grechanyk M , Kuryata O 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: None. Main funding source(s): -

Objective
To estimate the frequency of postprandial hypertriglyceridemia (PPG), levels of leptin, carotid intima-media thickness in patients with coronary artery disease (CHD) combined with nonalcoholic liver steatosis (NALS).

Methods
We studied 61 patients with CHD in combination with NALS mean age 57,8±2,04 (group A) and 20 patients with CHD without NALS mean age 56,6±4,6 (group B). Patients with diabetes were excluded. Studied PPG, levels of leptin and carotid intima-media thickness.

Results
Revealed an increase in the level of triglycerides after fat load test in group A by 57% (from 2.27 [1.74; 2.77] mmol/l to 3.56 [2.60; 4.89] mmol/l), in the group B by 203% (s 1.24 [1.05; 1.86] mmol/l to 3.76 [1.64; 5.51] mmol/l). In patients in a group A identified the highest leptin levels 20,9 [12,3; 24,6] ng/ml than in a group B- 13,2 [7,3; 16,9] ng/ml, (p &lt;0,02). Carotid wall thickness was lower in a group A (0,14±0,02 cm) than in a group B (0,16±0,01 cm, p =0,01). Frequency of exposure of atherosclerotic carotid plaques in a group A – 82%, was higher than in a group B – 64% (p &lt;0,05). In group A unstable plaques found significantly more often (31%, p = 0,01), than in the control group B (8%). There was correlation between PPG and unstable plaques (r=0,75, p=0,03) in a subgroup with obesity grade 2.

Conclusion
The incidence of unstable atherosclerotic plaques of carotid arteries in the group with CAD and NALS was higher (34%) unlike patients with CAD without NALS (5%). It has been shown for the first time that under the conditions of the combined course of CAD with liver steatosis, an increase in body weight is associated with a reduced reaction of postprandial TG levels with an increase in leptin levels. According to the results of ROC analysis of significant predictors of liver steatosis in the group of patients with CAD were levels of leptin (AUC for leptin – 0.69 (0.56-0.82)).
Virus specific CD8+ T-cells accumulate, but do not recognize antigen, in the atherosclerotic lesion
Authors: De Jong M , Depuydt MAC , Lozano Vigario F , Van Veelen PA , Kuiper J , Slutter BA 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ERA CVD
Dutch Heart Foundation
Viral infections have been associated with the progression of atherosclerosis. CD8+ T-cells directed against common viruses, such as influenza and Epstein-Barr virus, have been detected inside of human atherosclerotic lesions. These virus specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis, however, their mechanism of action in the atherosclerotic lesion remains unclear. This study aimed to characterize the behavior of virus specific CD8+ T-cells in the atherosclerotic lesion.
The presence of virus specific CD8+ T-cells in atherosclerotic lesions was assessed by performing T-cell receptor (TCR)-β sequencing on human endarterectomy samples and patient matched blood samples (N=10). These TCRs were subsequently compared to known virus specific TCR sequences. Virus specific CD8+ T-cells seemed to accumulate in the atherosclerotic lesion (mean=3.5%), compared to patient matched blood samples (mean=2.0%) (p=0.053). Moreover, these virus specific CD8+ T-cells produced significantly more IFN-γ (p=0.0009) and Granzyme B (p=0.0038) in response to external stimuli, suggesting these T-cells may play a pro-inflammatory role in the pathogenesis of atherosclerosis.
To investigate if virus specific CD8+ T-cells can be stimulated in situ, the immunopeptidome of 51 pooled human plaques was determined and matched with various viral peptidomes. Only one peptide presented in the atherosclerotic lesions matched a viral peptidome, rendering almost all virus specific CD8+ T-cells in the lesion antigen non-specific.
In conclusion, virus specific CD8+ T-cells are enriched in atherosclerotic lesions and have an activated phenotype, compared to other plaque residing CD8+ T-cells. The absence of virus specific antigen presentation in the atherosclerotic lesion suggests that if these CD8+ T-cells contribute to inflammation, they do so in an antigen independent manner.
Granzyme B+ CD4+ T cells associate with an unstable plaque phenotype in advanced human atherosclerosis
Authors: Depuydt MAC , Smit V , Lozano Vigario F , Bernabe Kleijn MNA , De Vries MR , Quax PHA , Wezel A , Smeets HJ , Kuiper J , Foks AC , Bot I , Slutter B 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): The Dutch Heart Foundation
Cytotoxic CD4+ T cells have previously been found in peripheral blood of patients with coronary artery disease (1), however their occurrence in atherosclerotic plaques and their association with the pathophysiology of atherosclerosis has not been established.
Single-cell RNA sequencing was performed on human carotid atherosclerotic plaques of 18 patients to identify specific T cell populations (2). Next, human femoral and carotid atherosclerotic plaques (n=95) and matched blood samples (n=49) were analyzed by flow cytometry for the presence of CD4+GZMB+ T cells. Plaque morphology was assessed by Movat’s Pentachrome staining.
A distinct cytotoxic GZMB+ PRF1+ CD28- CD4+ T cell cluster was identified using single-cell RNA sequencing. Furthermore, flow cytometry analysis showed that the percentage of GZMB+CD4+ T cells was significantly elevated in plaque compared to blood (Blood: 12.17±2.0 vs. Plaque: 17.40±1.0; P=0.0002). Moreover, a significant positive correlation was observed between the percentage of GZMB+CD4+ T cells in blood versus plaque (P=0.031). In line with the proinflammatory character of these cells, we found a positive association of GZMB+CD4+ T cells (P=0.036) with necrotic core size, whereas no correlation was found with this subtype in the circulation.
In this study we have shown an enrichment of cytotoxic CD4+ T cells in atherosclerotic lesions, which positively correlate with necrotic core size. Future studies are aimed at elucidating the role of these cells in advanced atherosclerosis.
The C-type Natriuretic Peptide: a new player in the development of the Marfan syndrome?
Authors: Clerc S , Bielmann C , Bouzourene K , Deglise T , Mazzolai L , Rosenblatt-Velin N 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public hospital(s). Main funding source(s): CHUV

Background
Marfan Syndrome (MFS) is an autosomal dominant inherited connective tissue disorder affecting the cardio-vascular system. Aortic dissections and ruptures are the primary cause of morbidity and mortality in these patients. MFS is a genetic disorder due to mutations in the Fibrillin1 gene or in genes coding for the proteins of the TGF-beta signaling pathway. No treatment really cures Marfan patients.
Interestingly, in humans, mutations in the gene coding for the C-type natriuretic peptide (CNP) or its receptors lead to a "Marfan-like syndrome". CNP is a local regulator of skeletal growth and of vascular homeostasis, remodeling and angiogenesis. CNP binds to two receptors, NPR-B and NPR-C, expressed on endothelial and smooth muscle cells (SMCs). CNP is constitutively released by endothelial cells, whereas TGF-beta stimulates its secretion by SMCs.
The aim of this project is to determine whether altered CNP signaling pathway contributes to the development and progression of the vascular dysfunctions in MFS.

Methods
Plasma and vessel biopsies were taken from Marfan patients (RAVAD registery, CHUV Lausanne) and from Fbn1C1041G/+ mice, a mouse model which recapitulates several of the human phenotypes, including aortic wall degeneration and aneurysm development. CNP and TGF-beta concentrations were measured in the plasma. CNP, NPR-B and NPR-C protein levels were evaluated by Western blot analysis in aortic tissue during the development of MFS. In parallel, human and mouse SMCs were isolated and cultured in vitro with different CNP concentrations.

Results
CNP plasma concentration was decreased in Marfan patients compared to age and sex-matched non-Marfan patients (18 pmol/l versus 310; p=0.07). Two fold less CNP protein level was detected in the abdominal aorta of a Marfan patient.
In 6-7 week-old male Fbn1C1041G/+ mice, CNP protein levels were 1.5 and 2.5-fold increased in the ascending and descending aorta, respectively. NPR-B and NPR-C protein levels remained unchanged. In 24 week-old Marfan male mice, CNP protein level was normalized. In female mice, we detected no alterations of the CNP protein level but the NPR-B and NPR-C protein levels were decreased in the descending aorta 6 and 24 weeks after birth, respectively. In vitro, CNP simulates both human and mouse SMC proliferation in a dose-dependent manner (+ 40% for human SMCs stimulated with 0.02 nM CNP).

Conclusion
Our results suggest that the early step of the syndrome is associated with high level of CNP (detected in 6 week-old male mice), whereas the late advanced stage of the disease is associated with decreased CNP protein level (detected in Marfan patients). These results could open the door to new therapies for Marfan patients.
Ivabradine rescues vascular abnormalities in a mouse model of duchenne muscular dystrophy
Authors: Acar E , Kuruppu Appuhamilage M , Szabo PL , Trojanek S , Abraham D , Hilber K , Podesser BK , Kiss A 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds zur Förderung der wissenschaftlichen Forschung
Ivabradine rescues vascular abnormalities in a mouse model of muscular dystrophy

Background
Duchenne muscular dystrophy (DMD) is a rare genetic disorder that primarily affects boys, initiated by the absence of dystrophin and is mainly differentiated by skeletal muscle degeneration and cardiac dysfunction. However, recent studies have underlined the importance of vascular abnormalities such as augmented arterial stiffness and endothelial dysfunction in the progression of cardiac complications in DMD. Several pleiotropic effects of ivabradine have been identified, including the reduction of vascular complications in coronary artery and ischemic heart disease patients. Nevertheless, whether chronic ivabradine treatment could improve the vascular complications in DMD is largely unknown.

Methods
In this study, vascular abnormalities in both dystrophin and utrophin deficient (mdx-utr KO) mice were examined, a severe and progressive animal model of DMD. Mice (4-6 weeks old) were subjected to ivabradine (10 mg/kg/day in drinking water) or vehicle treatments for 3 to 4 weeks. At the end of the treatment, aorta and lung tissue were collected to assess the vascular reactivity by wire myograph and the activity of angiotensin-converting enzyme (ACE) activity was measured in lung tissue respectively.

Results
Comparable with DMD patients, mdx-utr KO mice also exhibit vascular abnormalities and cardiac fibrosis. Ivabradine-treated mice showed a significantly improved endothelium-dependent vasodilation (p&lt;0.05) and decreased vascular stiffness compared to vehicle-treated animals (p&lt;0.01). In addition, lung ACE activity was significantly reduced in the treated mice in comparison to the control group (p&lt;0.01) indicating less activation in the renin-angiotensin-aldosterone system, which causative plays role in the progression of vascular and cardiac dysfunction.

Conclusions
In conclusion, our study shows for the first time the beneficial effects of chronic ivabradine treatment on the progression of cardiac vascular complications in DMD and this may present a novel therapeutic approach. Further studies are needed to clarify the underling signalling mechanisms.
Dissecting the progression of cardiac dysfunction in tumor-bearing mice
Authors: Dostal C , Szabo LP , Aioanei C , Abraham D , Zins K , Bakiri L , Wagner E , Podesser BK , Kiss A 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Cancer patients undergoing heart-related complications result in high incidences of mortality. Nevertheless, it is still not fully understood whether localized tumors affect heart function prior to the onset of cachexia, hence, making the heart more vulnerable for functional abnormalities in later stages of the disease. In addition to analyse heart function, we focus on the expression BCL-2–associated athanogene 3 (BAG3), a co-chaperone protein and Hsp70, which are highly expressed in tumor but decrease in cardiomyocytes (CM) in heart failure (HF).

Methods
Colon-26 adenocarcinoma cells (C26; n=22) with/without shIL-6 (C26 shIL-6; n=22) were injected subcutaneously into the right flank of 10-11 weeks old BALB/c male mice. Control mice were injected with vehicle (PBS; n=8). Cardiac function was assessed by echocardiography and invasive hemodynamic measurements 10 (early) and 20 (late) days after the injection, respectively. In addition, the expression of BAG3 and Hsp70 were determined by Western blot as well as the extend of cardiac fibrosis was determined by Masson-Goldner's trichrome staining.

Results
The tumor size was comparable between the two injected groups. However, only C26 group showed a significant loss of subcutaneous fat and skeletal muscle (p&lt;0.05, respectively), suggesting cachexia. Heart weight normalized to tibia length was not changed in the injected groups as compared to controls (day 20). However, left ventricular ejection fraction (LVEF) showed a tendency to decline in the early phase (p~0.08) in both injected group and it reached significance at late stage (p&lt;0.05). Invasive hemodynamic assessment also confirmed the contractile dysfunction, resulting in a decrease in LV systolic pressure and increase of LV end-diastolic pressure (p&lt;0.05, respectively). Importantly, these functional changes in the heart in tumor-bearing mice were associated with a marked reduction in both BAG3 and Hsp70 in the myocardium. Furthermore, there was no sign of cardiac fibrosis in the injected groups.

Discussion
Our study shows for the first time that tumor rather than cancer cachexia plays a significant maladaptive role in the progression of cardiac dysfunction in a mouse model of C26 injection-induced cachexia. The progression of cardiac contractile dysfunction was associated with a decline in BAG3 and Hsp70 in tumor-bearing mice, suggesting changes of BAG3/Hsp 70 signalling may be a critical component as well as target.
Multivessel vs. culprit-vessel only percutaneous coronary interventions in acute myocardial infarction and cardiogenic shock: a systematic review and meta-analysis of prospective randomized and retrospective studies
Authors: Gill Gauravpal S , Sánchez Jorge Sanz , Thandra Abhishek , Kanmanthareddy Arun , Alla Venkata Mahesh , Garcia-Garcia Hector M 
Published: June 2022

Abstract

Aims
Studies comparing outcomes of multivessel (MV) vs. culprit-vessel (CV) only percutaneous coronary intervention (PCI) during index cardiac catheterization in patients presenting with acute myocardial infarction (MI) and cardiogenic shock (CS) have reported conflicting results. In this systematic review we aim to investigate outcomes with MV vs. CV-only revascularization strategies in patients with acute MI and CS.

Methods and results
PubMed, Google Scholar, CINAHL and Cochrane databases were queried for studies comparing MV vs. CV PCI in patients with acute MI and CS. Data were extracted and pooled by means of random effects model. Primary outcome was early all-cause mortality (up to 30 days), while the secondary outcomes included late all-cause mortality (mean, 11.4 months), stroke, new renal replacement therapy, reinfarction, repeat revascularization, and bleeding. Pooled odds ratio (OR), 95% confidence intervals (CIs), and number needed to harm (NNH) were calculated. A total of 16 studies enrolling 75  431 patients were included. The MV PCI was associated with higher risk of early mortality [OR 1.17, 95% CI (1.00–1.35); P = 0.04; NNH = 62], stroke [1.15 (1.03–1.29); P = 0.01; NNH = 351], and new renal replacement therapy [1.33 (1.06–1.67); P = 0.01; NNH = 61]; and with lower risk of repeat revascularization [0.61 (0.41–0.89); P = 0.01] when compared with CV PCI. No significant difference was observed in late-term mortality [1.02 (0.84–1.25); P = 0.84], risk of reinfarction [1.13 (0.94–1.35); P = 0.18], or bleeding [1.21 (0.94–1.55); P = 0.13] between groups.

Conclusion
Among patients with acute MI and CS, MV PCI during index cardiac catheterization was associated with higher risk of early mortality, stroke, and renal replacement therapy.
Impact of multicomponent integrated care on mortality and hospitalization after acute coronary syndrome: a systematic review and meta-analysis
Authors: Hoo Jia-Xin , Yang Ya-Feng , Tan Jia-Yin , Yang Jingli , Yang Aimin , Lim Lee-Ling 
Published: June 2022

Abstract

Aims
Multicomponent integrated care is associated with sustained control of multiple cardiometabolic risk factors among patients with type 2 diabetes. There is a lack of data in patients with acute coronary syndrome (ACS). We aimed to examine its efficacy on mortality and hospitalization outcomes among patients with ACS in outpatient settings.

Methods and results
A literature search was conducted on PubMed, EMBASE, Ovid, and Cochrane library databases for randomized controlled trials, published in English language between January 1980 and November 2020. Multicomponent integrated care defined as two or more quality improvement strategies targeting different domains (the healthcare system, healthcare providers, and patients) for one month or more. The study outcomes were all-cause and cardiovascular-related mortality, hospitalization, and emergency department visits. We pooled the risk ratio (RR) with 95% confidence interval (CI) for the association between multicomponent integrated care and study outcomes using the Mantel–Haenszel test. 74 trials (n = 93 278 patients with ACS) were eligible. The most common quality improvement strategies were team change (83.8%), patient education (62.2%), and facilitated patient-provider relay (54.1%). Compared with usual care, multicomponent integrated care was associated with reduced risks for all-cause mortality (RR 0.83, 95% CI 0.77–0.90; P &lt; 0.001; I2 = 0%), cardiovascular mortality (RR 0.81, 95% CI 0.73–0.89; P &lt; 0.001; I2 = 24%) and all-cause hospitalization (RR 0.88, 95 % CI, 0.78–0.99; P = 0.040; I2 = 58%). The associations of multicomponent integrated care with cardiovascular-related hospitalization, emergency department visits and unplanned outpatient visits were not statistically significant.

Conclusion
In outpatient settings, multicomponent integrated care can reduce risks for mortality and hospitalization in patients with ACS.
Widespread genomic signatures of reproductive isolation and sex-specific selection in the Eastern Yellow Robin, Eopsaltria australis
Authors: Kvistad Lynna , Falk Stephanie , Austin Lana 
Published: June 2022

Abstract
How new species evolve is one of the most fundamental questions in biology. Population divergence, which may lead to speciation, may be occurring in the Eastern Yellow Robin, a common passerine that lives along the eastern coast of Australia. This species is composed of 2 parapatric lineages that have highly divergent mitochondrial DNA; however, similar levels of divergence have not been observed in the nuclear genome. Here we re-examine the nuclear genomes of these mitolineages to test potential mechanisms underlying the discordance between nuclear and mitochondrial divergence. We find that nuclear admixture occurs in a narrow hybrid zone, although the majority of markers across the genome show evidence of reproductive isolation between populations of opposing mitolineages. There is an 8 MB section of a previously identified putative neo-sex chromosome that is highly diverged between allopatric but not parapatric populations, which may be the result of a chromosomal inversion. The neo-sex chromosomal nature of this region, as well as the geographic patterns in which it exhibits divergence, suggest it is unlikely to be contributing to reproductive isolation through mitonuclear incompatibilities as reported in earlier studies. In addition, there are sex differences in the number of markers that are differentiated between populations of opposite mitolineages, with greater differentiation occurring in females, which are heterozygous, than males. These results suggest that, despite the absence of previously observed assortative mating, mitolineages of Eastern Yellow Robin experience at least some postzygotic isolation from each other, in a pattern consistent with Haldane’s Rule.
‘The Black Sea Is Our Mallorca’: The Making of the Tourist Experience in the German Democratic Republic
Authors: López-Barajas José Luis Aguilar 
Published: June 2022

Abstract
This article analyses the construction of the East German holiday experience in the 1960s and 1970s, when tourism became a mass phenomenon on both sides of the Iron Curtain. First, it discusses the role played by the West in shaping the expectations of GDR tourists. Mallorca was the ultimate, but not sole, destination, that influenced how East Germans imagined tourism abroad. Secondly, the article tackles how expectations compared with actual experiences. State surveillance, scarcity and lack of means were common challenges that East Germans had to face and clashed with the glittering image of tourism with which they were inundated from West Germany. The Bulgarian Black Sea emerged as a substitute for that Western tourism as other possibilities, such as socialist Cuba or Yugoslavia, were limited. Touring in Bulgaria became a long-lasting experience. The article approaches the multiple meanings of this type of vacation abroad. Political, experiential and personal implications shaped East Germans’ holidays and entangled experiences and expectations, and the article provides a broad understanding of the meanings of vacation and tourism for citizens of East Germany.