bluuebunny/crossref_metadata_2025_split huggingface dataset:
Academic spam mails from “Predatory Journals” in cardiology: a cross-sectional study over 3 months
Authors: Ohlow M 
Published: October 2022

Abstract

Background
Numerous online journals are referred to as predatory journals because their efforts are focused primarily on collecting publication fees rather than on content, peer review, or manuscript presentation. Many of these journals send Academic Spam Mails (ASM), requesting manuscript submissions.

Purpose/Methods
Over a 3-month period, all ASMs addressed to the author were collected and analyzed. A fake publication was created with a commonly used structure (Introduction, Methods, Results and Discussion). The article just repeated the phrase “Please get me off your mailing list” over and over again. This publication was submitted in response to each request to test the control mechanisms of the respective journals.

Results
During the study period, excluding duplicate requests, 125 ASMs (average 2.1 per business day) were received from a wide variety of journals spanning 38 different subject areas, of which 29/38 (76.4%) were from the medical field. 16/125 (16%) were related to a previously published article but not among the author's most important publications (median h-index rank 22; range 10–138). The majority (73.6%) of journals were listed in Beall's predatory journal list, only an absolute minority (0.8%) were listed in the Directory of Open Access Journals, and 96% were not listed in PubMed. Original papers (94.4%), reviews (88.0%), and case reports (87.2%) were most frequently requested; the publication charge (APC) was a median of $1,199 (range $50–3,586); in about 22% of cases, it was not apparent whether APCs were charged and, if so, how much. For the 125 nonsense publications sent out, there was a response in 16/125 (13%) (6 acknowledgements of receipt, 3 apologies, 2 the journal comments that the publication consisted of only one sentence, and 5 other responses). Interestingly, in one case editorial board members had also created a nonsense publication titled: “Ok we not send mail to you” and sent it to the author. 21.6% of the journals had sent ASM to the author again during the next months.

Conclusions
Academic spam mails from “predatory” online journals are a common problem. They are recognizable by their appearance in warning lists or non-appearance in directories of reputable open access journals. A placement of a nonsense publication in such a “predatory journal” was not successful.

Funding Acknowledgement
Type of funding sources: None.
ZNF259 rs964184 variant is associated with dyslipidemia and coronary artery disease in the young population
Authors: Santos M , Mendonca M I , Sa D , Temtem M , Sousa A C , Henriques E , Rodrigues M , Freitas S , Borges S , Guerra G , Freitas A I , Ornelas I , Drumond A , Palma Dos Reis R 
Published: October 2022

Abstract

Introduction
Coronary artery disease (CAD) is a dynamic inflammatory disease caused by atherosclerosis. GWAS showed that ZNF259 rs964184 encoding zinc finger protein (ZPR1) was associated with dyslipidemia and CAD. Recent research found that ZPR1 transcription is up-regulated in the brain of mice fed a high-fat diet, influencing the cell cycle, apoptosis, and RNA metabolism in neurons. This process at the heart vessels may increase oxidative stress and CAD.

Purpose
Study the association between the ZNF259 rs964184 C&gt;G polymorphism with dyslipidemia and CAD susceptibility in a Portuguese population.

Methods
A case-control study was performed with 3,160 individuals, namely 1,723 CAD patients (mean age 53.3±7.9; 78.7% male) and 1,437 controls (mean age 52.8±7.8; 76.3% male). Participants were stratified into two age groups (&lt;45 and &gt;55 years). ZNF259 rs964184 C&gt;G was genotyped and analysed using the dominant model (CG+GG vs CC). Multivariate logistic regression was performed in both age groups to investigate whether rs964184 polymorphism was associated with dyslipidemia and CAD susceptibility.

Results
The dominant model of ZNF259 was associated with dyslipidemia (OR=1.85; 95% CI: 1.22–2.79; p=0.003) and CAD (OR=1.46; 95% CI: 1.02–2.09; p=0.036) in the younger population under 45 years. In the &gt;55 years group, this model was associated with dyslipidemia (OR 1.46; 95% CI: 1.06–2.01; p=0.020) but not with CAD. After multivariate logistic regression, the CG+GG remained an independent risk factor for CAD susceptibility only in the population &lt;45 years (OR=1.60; 95% CI: 1.03–2.50; p=0.037).

Conclusion
ZNF259 rs964184 is a risk factor for dyslipidemia in the whole population. Dyslipidemia may up-regulate ZPR1 transcription, enhancing the vulnerability of coronary endothelial cells to both oxidative stress and inflammatory response, increasing CAD susceptibility. This mechanism seems more relevant at the cellular level in young patients representing a possible prophylactic and therapeutic target, especially in this age group.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM
Syndromic cardiac disorder is associated with a non-coding deletion that induces a 3D chromatin remodeling and PITX2 expression dysregulation
Authors: Baudic M , Murata H , Bosada F M , Souto Melo U , Aizawa T , Guedon A , Lindenbaum P , Gourraud J B , Makita N , Mundlos S , Christoffels V M , Makiyama T , Probst V , Schott J J , Barc J 
Published: October 2022

Abstract

In a first family (family#1), we identified 53 members of whom 17 present a syndromic cardiac disorder characterized by electrical disorders (sinus node dysfunction, atrial fibrillation...) and developmental defects (atrial septal defect, valvopathy, left ventricle non-compaction...) following an autosomal dominant model. Among the affected family members, 6 are implanted with a pacemaker and one experienced a sudden death at 43yo. Despite a strong linkage pointing to the 4q25 region, exome sequencing failed to identify causal variant. Interestingly, 6 additional non-related families presenting the same phenotype have been also identified.
Our aims are to identity the causal mutation and the molecular mechanism underlying this complex cardiac syndrome.
Genetic study has been performed using whole genome sequencing (WGS). Based on transgenic mouse strains, we assessed the impact of Family#1 mutation on the phenotype and on gene expression. Then, we generated human cardiomyocytes derived iPS cells (CM-iPS) isogenic models to evaluate the epigenome (CUT&RUN and ATAC-seq), transcriptome (RNA-seq) and topological associated domain (TAD) remodelling (Hi-C).
By WGS we uncovered a deletion of 15kb in a gene desert area on 4q25, segregating in all affected relatives of Family#1. The 6 other families present overlapping deletions. Mouse model recapitulates the cardiac phenotype and exhibit a dysregulation of Pitx2 expression in cardiac specific compartments. Based on human CM-iPS models, epigenetic data highlight among the 15kb deletion a unique open region containing a CTCF binding site, crucial for delimiting TAD boundaries. Hi-C assay reveals the fusion of 2 TADs and highlights new interactions between PITX2 and atrial specific regulatory elements.
We identified a deletion located within a gene desert area associated with a complex cardiac disorder. The CTCF binding site contained in the deletion seems key in the TAD border. The TAD remodelling leads to new (regulatory) interactions and expression dysregulation of PITX2. We describe a new molecular mechanism implying a yet unidentified non-coding regulatory element of PITX2 and responsible for a complex electrical and developmental cardiac syndrome.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Nantes UniversitéFrench national reserch agency (ANR)
PDE1 inhibition and adenosine A2A receptor activation synergistically potentiates spontaneous calcium waves and transients in mouse ventricular myocytes
Authors: Casabella-Ramon S , Jimenez-Sabado V , Hove-Madsen L 
Published: October 2022

Abstract

Background
The phosphodiesterase-1C (PDE1C) and the adenosine A2A receptor (A2AR) are located in a macromolecular cluster and expected to modulate cAMP-dependent regulation of the intracellular calcium homeostasis in cardiac myocytes. In this contect, atrial fibrillation has been associated with a high incidence of spontanoeus arrhythmogenic calcium waves caused by excessive A2AR activation. On the other hand, inhibition of PDE1C and A2AR activation has also been reported to produce a synergistic and protective effect on cardiomyocyte survival, but little is known about the corresponding effects on the intracellular calcium homeostasis.

Purpose
This study, therfore, aimed to investigate how PDE1 inhibition and/or A2AR activation modulate sarcoplasmic reticulum (SR) calcium homeostasis in mouse ventricular myocytes.

Methods
Mouse ventricular myocytes (47 cells from 20 mice) were loaded with the calcium indicator Rhod-2 and spontaneous calcium release events at rest or caffeine induced calcium transients were visualized using resonance-scanning confocal microscopy at a frame rate of 150 Hz. The SR calcium content was estimated as the ratio of the peak fluorescence and the fluoresence the end of a 10 mM caffeine pulse (20s). Calcium leak was estimated as ratio of the flourescence emmision at baseline before and at the end of the caffeine pulse.

Results
The incidence of spontaneous calcium waves or transients increased from 0.7±0.3 events/min in control to 1.1±0.5 events/min and 3.4±1.0 events/min (p&lt;0.01) after inhibition of PDE1 with the selective antagonist ITI-214 and the A2AR agonist CGS-21680 respectively. Concomitant PDE1 inhibition and A2AR activation synergistically increased the event frequency to 8.4±2.3 events/min (p&lt;0.05). There were no significant differences in the corresponding SR calcium contents (4.4±0.3, 4.5±0.4, 4.7±0.4 and 4.1±0.2 for control, ITI-214, CGS-21680 and ITI-214+CGS-21680 respectively). However, there was a parallel increase in calcium leak from 8.7±4.2% in control to 21.8±9.8% with ITI-214, 17.6±7.2% with CGS-21680 and 37.5±11.1% when myocytes were exposed to both compounds (p&lt;0.05), suggesting that the higher incidence of spontaneous calcium waves and transients observed upon PDE1 inhibition and/or A2AR activation is likely caused by a lowering of the threshold for spontaneous SR calcium release rather than by SR calcium overloading.

Conclusion
PDE1 inhibition exacerbates the incidence of spontaneous arrhythmogenic SR calcium release events in myocytes with high levels of A2AR activation, suggesting that PDE1 inhibition under these conditions increases the risk of arrhythmia.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation
Cardiomyocytes derived small extracellular vesicles plays an important role in heart development
Authors: Balbi C , Ceresa D , Schiano C , Malatesta P , Barile L , Vassalli G 
Published: October 2022

Abstract

Introduction
Neonatal rats have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation.
Extracellular vesicles (EV) are bilayer-membrane nanoparticles released by all cell types, carrying proteins, lipids, and nucleic acids, which reflect the activation state of parental cells. Secreted small extracellular vesicles (sEV), prominently figure among extracellular signals that regulate cell function.

Purpose
We aim to determine whether cardiomyocyte (CM) derived sEV carried miRNA that has a role in heart development with specific regards to cardiomyocyte maturation.

Methods
sEV were isolated from rat cardiomyocyte at day 0 and 7 after birth by serial ultracentrifugation. sEV were characterized by NTA and analyzed by Western blot for the presence of classical EV markers (TSG101, Syntenin-1). The role of sEV in cardiomyocyte proliferation was assessed by analysis of EdU incorporation on neoantal rat CM treated with sEV_p0 or sEV_p7. miRNA content on sEV was assessed using a rat-miRNome MicroRNA Profiling Kit and the identified miRNA's targets confirmed by RealTime-PCR and Western Blot.

Results
NTA and Western Blot analysis confirmed the presence of sEV in both the extracellular vesicles preparation. sEV_p0 showed to be able to sligtly increase EdU incorporation in treated cardiomyocyte (1.15-Fold) while sEV_p7 significantly inihibit CM proliferation (0.78-Fold) toghether with a change in cardiomyocyte citoscheletal architecture. Data from miRNome analysis showed in sEV_p7 a significan increase in miRNA with cyclines as tagets. Downregulation of Cdk1; Cdk4; Cdk2; CcnB1 and CcnD1 was confirmed on CM trated with sEV_p7 compared to Ctrl. Downregulation of CCND1 was aslo confrmed at the protein level by Western Blot analysis.

Conclusions
These preliminary resultes showed an important role in heart develompent of cardiomyocyte derived-sEV. A deeper investigation of the pathaway activated by sEV may have a potential interest for the identification of possible regulators for stimulating heart regeneration.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Fondazione Leonardo, Lugano, Switzerland
Programmed cell death protein 1 (PD1) deficiency induces cardiac inflammation during baseline conditions and ischemia/reperfusion injury
Authors: Michel L , Korste S , Spomer A , Stock P , Odersky A , Hendgen-Cotta U B , Rassaf T , Totzeck M 
Published: October 2022

Abstract

Background
The Programmed cell death protein 1 (PD1) immune checkpoint is densely expressed on cardiac endothelial cells. The increasing clinical application of immune checkpoint inhibitor therapy targeting PD1 for the treatment of advanced malignancies has revealed profound cardiovascular side effects that have recently paralleled in a preclinical model. However, the effects of PD1 deficiency during baseline conditions and myocardial injury are so far unknown.

Purpose
This study aims to assess the impact of PD1 deficiency on myocardia immunity, and to evaluate the relevance of PD1 signalling in cardiac disease.

Methods
C57BL/6J wild-type mice and C57BL/6J Pdcd1−/− mice were purchased and bred at the animal facility. In-vivo ischaemia/reperfusion (I/R) injury was applied to assess the response in cardiac injury. In brief, mice were anesthetised followed by lateral thoracotomy and ligation of the left coronary artery for 45 min. For flow cytometry, hearts were removed and subjected to an enzymatic digestion. Single cell solutions were stained with different antibody panels to assess cardiac immune cells and the expression of programmed cell death protein 1 ligand 1 (PDL1). Western blot was conducted after homogenization of snap-frozen heart tissue using specific primary and corresponding secondary antibodies. Immunofluorescence and conventional haematoxylin and eosin stain from 4 μm sections were used to visualize the distribution of PDL1 in cardiac tissue.

Results
While no overt cardiac phenotype was observed in Pdcd1−/− mice, a profound upregulation of pro-inflammatory cytokines was determined during baseline conditions, including interleukin (IL) 1α IL4, and extracellular-signal regulated kinase (ERK) 1/2. NADPH oxidase 1 (NOX1) which is involved in production of reactive oxygen species and endothelial injury response was downregulated in Pdcd1−/− mice. Following I/R injury, a significant decline in endothelial PDL1 expression was observed, which was attributed to changes in the area at risk, as shown by immunofluorescence staining. The infarct size following in-vivo I/R injury was not altered upon PD1-deficiency as determined by TTC staining. However, flow cytometry determined increased cell numbers of distinct leukocyte subsets during reperfusion-related inflammation.

Conclusion
Deficiency of PD1/PDL1 signalling shows distinct inflammatory changes in cardiac tissue at baseline and I/R injury. The results indicate that relevant PD1-related detrimental effects are not limited to complications from cancer therapy but can be expected in various forms of cardiovascular disease, hence requiring further investigations.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Germany
The peri-infarct gray zone of myocardial fibrosis is a better predictor of ventricular arrhythmias than dense core fibrosis in patients with previous myocardial infarction
Authors: Lopes P , Cunha G , Freitas P , Rocha B , Abecasis J , Carmo J , Guerreiro S , Galvao Santos P , Moscoso Costa F , Carmo P , Cavaco D , Morgado F , Mendes M , Adragao P , Ferreira A 
Published: October 2022

Abstract

Background
Current sudden cardiac death (SCD) risk stratification relies heavily on left ventricular ejection fraction (LVEF), but markers to refine risk assessment are needed. Dense core fibrosis (DCF) and peri-infarct “gray zone” of myocardial fibrosis (GZF) on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) have been proposed as potential arrhythmogenic substrates. The aim of our study was to determine whether DCF and GZF could predict the occurrence of ventricular arrhythmias in patients with previous myocardial infarction.

Methods
We performed a single centre retrospective study enrolling consecutive patients with previous myocardial infarction undergoing CMR before implantable cardioverter-defibrillator (ICD) implantation. Areas of LGE were subdivided into “core” DCF and “peri-infarct” GZF zones based on signal intensity (&gt;5 SD, and 2–5 SD above the mean of reference myocardium, respectively).
The primary endpoint was a composite of sudden arrhythmic death, appropriate ICD shock, ventricular fibrillation (VF), or sustained ventricular tachycardia (VT) as detected by the device.

Results
A total of 88 patients (median age 61 years [IQR 54–73], 84% male, median LVEF 30% [IQR 23–36%], 14% secondary prevention) were included. During a median follow-up of 23 months [IQR 9–38], 13 patients reached the primary endpoint (10 appropriate ICD shock, 2 sustained VT or VF, and 1 sudden arrhythmic death). Patients who attained the primary endpoint had similar DCF (30.4±14.7 g vs. 28.0±15.3 g; P=0.601) but a greater amount of GZF (18.1±9.6 g vs. 11.9±6.7 g; P=0.005). On univariate analysis, GZF was associated with the composite endpoint (HR: 1.09 per gram; 95% CI: 1.02–1.15; P=0.006), whereas DCF was not (HR: 1.01 per gram; 95% CI: 0.98–1.05; P=0.571). After adjustment for LVEF, GZF remained independently associated with the primary endpoint (adjusted HR: 1.06 per gram; 95% CI: 1.01–1.12; P=0.035). Decision tree analysis identified 11.9g of GZF as the best cut-off to predict life-threatening arrhythmic events. The primary endpoint occurred in 11 out of the 35 patients (31.4%) with GZF ≥11.9 g, but in only 2 of the 53 patients (3.8%) with GZF &lt;11.9 g – Figure 1.

Conclusions
The extent of peri-infarct GZF seems to be a better predictor of ventricular arrhythmias than DCF. This parameter may be useful to identify a subgroup of patients with previous myocardial infarction at increased risk of life-threatening arrhythmic events.

Funding Acknowledgement
Type of funding sources: None.
The long non-coding RNA Heat4 is dynamically regulated during cardiogenic shock
Authors: Winkler M , Kneuer J M , Meinecke T , Moebius-Winkler M N , Weiss R , Haas J , Garfias-Veitl T , Von Haehling S , Keller T , Thiele H , Lurz P , Speer T , Laufs U , Boeckel J N 
Published: October 2022

Abstract

Background and purpose
Cardiogenic shock (CS) remains the leading cause of death in acute myocardial infarction (AMI), with high mortality rates of 40–50%. The long non-coding RNA (lncRNA) Heat4 is associated with the inflammatory response of non-classical monocytes. Previous experimental work shows that this mechanism may be important in heart failure (HF) and during regeneration after vascular injury. Here, we investigate the association of Heat4 with survival in patients with chronic HF and assessed its regulation in AMI and CS.

Methods and results
Heat4 was elevated in the blood of HF patients compared to age-matched non-failing controls (+5.2-fold; HF: N=63; Controls: N=38; p&lt;0.05). Heat4 showed a positive correlation with systemic inflammation (hsCRP; r=0.41; p&lt;0.05) and was negatively associated with LVEF (r=−0.45; p&lt;0.001). Heat4 blood levels showed good discriminatory power for prevalence of HF (AUC = 0.734; p&lt;0.05) and mortality prediction after 4-year follow-up (AUC = 0.789; HF: Death N=32; Controls: Death N=0; p&lt;0.05). Furthermore, Heat4 was elevated in the blood of patients with AMI compared to controls (+1.85-fold; AMI: N=42; Controls: N=23; p&lt;0.05). Heat4 showed a very strong induction in patients suffering from CS (+284.5-fold; CS: N=4; Controls: N=5; p&lt;0.05). In agreement with an anti-inflammatory signaling, Heat4 showed a dynamic regulation in patients with CS with a 284.5-fold increase during acute shock and a decrease 24 hours after revascularization (−82.3% compared to day of revascularization). This regulation was validated in an independent second cohort.

Conclusion
The lncRNA Heat4 is upregulated in the blood of patients with chronic heart failure, acute myocardial infarction and cardiogenic shock. In CS, Heat4 is dynamically regulated. These data set the stage to further assess Heat4 blood levels as a strategy for risk stratification and potential treatment target in HF.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Projektfoerderung im Bereich der Herzmedizin, Leipzig