bluuebunny/crossref_metadata_2025_split huggingface dataset:
The selective late sodium current inhibitor eleclazine reduces atrial fibrillation dominant frequency and facilitates the suppression of arrhythmia in HL-1 cells
Authors: Del Canto Serrano I , Gomez-Cid L , De La Nava A.S , Guillem M.S , Fernandez-Santos M.E , Climent A.M , Atienza F , Fernandez-Aviles F , Chorro F.J 
Published: November 2020

Abstract

Background
The cardiac late sodium current (INaL) has been increasingly implicated in the initiation of atrial fibrillation (AF). In fact, it has been reported that the augmentation of INaL in pathophysiological conditions prolongs repolarization and facilitates the appearance of afterdepolarizations, which can act as triggers of arrhythmic activity. Eleclazine is a novel selective inhibitor of INaL and is undergoing clinical testing for the treatment of cardiac arrhythmias.

Purpose
The aim of this study was to investigate the effects of eleclazine on spectral characteristics of atrial fibrillation in cultured atrial myocyte monolayer in order to assess whether this inhibitor could protect against cardiac arrhythmias.

Methods
Confluent HL-1 murine atrial myocyte monolayer with spontaneous fibrillatory activity was cultured in 1.5 cm diameter petri dishes (n=10). A high-resolution optical mapping system was used to record fibrillatory activity under basal conditions (without drug), and under eleclazine at increasing concentrations (1, 3 and 5 μM). Power spectra of optical signals were estimated by using Welch periodogram and dominant frequency (frequency with the largest peak in the spectrum between 0.05 and 30 Hz) was determined. The incidence of spontaneous defibrillation was analyzed under control and drug conditions. An ANOVA and a chi-squared test were used. Significance was reached when p&lt;0.05.

Results
Eleclazine at 1, 3 and 5 μM significantly decreased dominant frequency with respect to basal conditions (basal: 4.74±1.31 Hz; 1μM: 3.59±1.17 Hz, p&lt;0.001; 3μM: 3.19±0.64 Hz, p&lt;0.01; 5μM: 2.58±0.40 Hz, p&lt;0.01). The magnitude of drug-induced decrease in AF activation frequency was enhanced by increasing concentrations (1μM: 27%, 3μM: 42%; 5μM: 46%; p&lt;0.05). After the analysis of optical signals, we observed that the incidence of spontaneous defibrillation in atrial monolayers was significantly greater under eleclazine 5μM action than under control conditions (chi-square=5.00, p=0.025). In fact, under the action of eleclazine 5μM, fibrillatory activity was suppressed in 4 of the 10 monolayers, phenomenon that did not occur in any case of control situation.

Conclusions
Selective late INa inhibition with eleclazine reduced dominant frequency of atrial fibrillation and facilitates the termination of arrhythmia in cultured atrial myocyte monolayer.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Ministerio de Innovaciόn y Ciencia, Spain; Generalitat Valenciana, Spain
A unique proteomic signature of extracellular vesicles derived from mesenchymal stromal cells of epicardial fat from patients with and without ischemic heart disease
Authors: Brzezinski R.Y , Tepper-Shaihov O , Naftali-Shani N , Zuroff E , Volvovitch D , Amunts S , Ram E , Sternik L , Raanani E , Grossman E , Leor J 
Published: November 2020

Abstract

Background
Mesenchymal stromal cells (MSCs) have been implicated in the development and progression of myocardial diseases. However, the role of extracellular vesicles (EVs) secreted from human MSCs (hMSCs) of epicardial fat (eFat) in the pathogenesis of ischemic heart disease (IHD) has never been studied.

Purpose
We sought to characterize EVs from eFat-hMSCs of patients with and without IHD.

Methods
We collected eFat specimens from 12 patients with (n=7) and without (n=5) IHD who underwent open heart surgery. We isolated and cultured hMSCs by enzymatic digestion and adherence to plastic. EVs were separated from the culture media by differential ultra-centrifugation. We assessed EV size and structure by electron microscopy and nanoparticle tracking analysis. Finally, we evaluated the proteomic profile of EVs from ischemic and non-ischemic patients by mass spectrometry.

Results
eFat-hMSCs from ischemic patients, secreted higher amounts of small EVs (size range of 70–200 nm) compared with non-ischemic controls (Figure 1A+B). Proteomic analysis revealed over 1,000 proteins inside isolated EVs. We identified 13 proteins that were significantly differentially expressed between patients with and without IHD, including apolipoprotein E, transforming growth factor-β and collagen α-1 (Figure 1C). We performed an enrichment analysis which showed that EVs from eFat-hMSCs from ischemic patients encapsulated functional protein networks associated with immune activation. Unlike IHD patients, EVs from non-ischemic patients carried functional protein networks that regulate angiogenesis.

Conclusions
eFat-hMSCs of patients with IHD secrete higher amounts of small EVs with a unique proteomic signature related to immune activation. EVs derived from eFat-hMSCs should be further studied for their potential role in the initiation and progression of cardiovascular diseases, such as coronary artery disease, heart failure and arrhythmias.
Figure 1

Funding Acknowledgement
Type of funding source: None
SIRT5 deficiency enhances the proliferative and therapeutic capacities of adipose-derived mesenchymal stem cell via metabolic switching
Authors: Ou T , Yang W , Li W , Lu Y , Dong Z , Sun A , Ge J 
Published: November 2020

Abstract

Background
Mesenchymal stem/stromal cells (MSCs) render potential therapies for multiple ischemic diseases. However, in vitro expansion of MSCs before application leads to a metabolic switch from glycolysis to oxidative phosphorylation, drastically impairing their proliferative and therapeutic capacities.

Purpose
Here we aim to identify the role of SIRT5, a master metabolic regulator, in culture expansion of adipose-derived MSCs (ADMSCs).

Methods
SIRT5 deficiencyADMSCs was obtained from Sirt5−/− mice and their metabolic pattern and proliferation capacity were tested during in vitro expansion. Hind limb ischemic model was established to evaluated the therapeutic function of Sirt5−/−ADMSCs.

Results
SIRT5 protein level was upregulated in ADMCSs undergoing culture expansion. Sirt5−/−ADMSCs during in vitro expansion exhibited higher proliferation rate, delayed senescence and enhanced antioxidant capacity. SIRT5 deficiency induced hypersuccinylation of metabolic-related proteins, leading to attenuated mitochondrial respiration with elevated glycolysis and pentose phosphate pathway. Furthermore, lowering succinylation level by glycine treatment reversed the altered metabolism and enhanced proliferation of Sirt5−/−ADMSCs. In mice hind limb ischemic model, SIRT5−/−ADMSCs treatment achieved better blood flow recovery and angiogenesis compared to WT ADMSCs treatment.

Conclusion
We reveal that SIRT5 is a key regulator of ADMSCs undergoing in vitro culture. Ablation of SIRT5 leads to reversed metabolic pattern, enhanced proliferative capacity and improved therapeutic outcomes. Our data provide a potential target for enhancing MSC functional properties during bio-manufacturing in future MSC therapy. Such work may not only benefit MSC cell therapy, but could extent to a wide variety of other stem cells that share similar metabolic pattern.
Graphic Abstract

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Major Research Plan of the National Natural Science Foundation of China. National Science Fund for Distinguished Young Scholars.
Cardiac recovery following left ventricular assist device therapy: experience of complete device explantation including ventricular patch plasty
Authors: Gyoten Takayuki , Rojas Sebastian V , Fox Henrik , Hata Masatoshi , Deutsch Marcus-André , Schramm René , Gummert Jan F , Morshuis Michiel 
Published: November 2020

Abstract

OBJECTIVES
Myocardial recovery is a rare phenomenon in left ventricular assist device (LVAD) therapy. Surgical LVAD removal is associated with the risk of cardiac failure, and the individual evaluation of sufficient myocardial recovery is crucial. Thus, complete device explantation is not consistently performed to minimize perioperative risk. However, the remaining ventricular assist device components bear significant risks of infection or thrombosis. Therefore, we developed this study to evaluate a complete LVAD explantation protocol.

METHODS
All patients in our institution who had an LVAD explanted were enrolled in the study. Explant surgery involved removal of the driveline, pump housing, sewing ring and outflow graft. The ventricular wall was reconstructed by double patch plasty. Our analysis focused on surgical and postoperative outcome parameters, including all-cause mortality and major adverse cardiac and cerebrovascular events.

RESULTS
A total of 12 patients (HVAD, n = 5; HeartMate II, n = 3; HeartMate 3, n = 4) had myocardial recovery and qualified for our LVAD explantation study protocol [median age: 40 years, interquartile range (IQR) 33–52 years; 50% men]. Primary heart failure aetiology: myocarditis (n = 5), dilated cardiomyopathy (n = 4), toxic cardiomyopathy (n = 2) and valvular heart failure (n = 1). The median average duration on LVAD was 10 months (25–75%: IQR 8.5–30 months). The median left ventricular ejection fraction was 15% (IQR 13–18%) at LVAD implantation and 50% (IQR 45–50%) before LVAD explantation (P = 0.0025).The 30-day survival was 100%. The 1-year survival was 91.7%. All patients were discharged after a median 13 days (IQR 10–18 days) postoperatively. No patient had major adverse cardiac and cerebrovascular events. The New York Heart Association functional class remained consistent during the follow-up period (median New York Heart Association functional class: II, IQR II–II class) including preservation of ventricular function.

CONCLUSIONS
Complete LVAD explantation with ventricular patch plasty is feasible and has consistent long-term results.
Enacting a queer pedagogy in the composition classroom
Authors: Buyserie Beth , Ramírez Ricardo 
Published: November 2020

Abstract
Adopting a queer pedagogy in composition classes that include diverse student populations can play an important role in promoting conversations on diversity and equity in the classroom. Under this approach, teachers and students are invited to question the connections between language, the body, power, and ethnicity, thus analysing how our language practices denote unique perceptions of the world. In this article, we intend to connect queer composition theory and pedagogies to a research experience to account for how teachers and students construct embodied and meaningful interactions in the composition class when they explore alternative queer forms of thinking and writing. To accomplish this goal, we foreground the work of queer composition scholars who question how our everyday language and writing practices shape our perception of other individuals and challenge us to consider how we mutually care for and respect each other’s language practices and raced bodies within our pedagogies.
Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome
Authors: Frustaci Andrea , Alfarano Maria , Verardo Romina , Agrati Chiara , Casetti Rita , Miraldi Fabio , Galea Nicola , Letizia Claudio , Chimenti Cristina 
Published: November 2020

Abstract

Aims
Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis which incidence, cause, and response to therapy is unreported.

Methods and results
Among 1916 patients with biopsy-proven myocarditis, 30 had NCV. Endomyocardial samples were retrospectively investigated with immunohistochemistry for toll-like receptor 4 (TLR4) and real-time polymerase chain reaction (PCR) for viral genomes. Serum samples were processed for anti-heart autoantibodies (Abs), IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α. Identification of an immunologic pathway (including virus-negativity, TLR4-, and Ab-positivity) was followed by immunosuppression. Myocarditis-NCV cohort was followed for 6 months with 2D-echo and/or cardiac magnetic resonance and compared with 60 Myocarditis patients and 30 controls. Increase in left ventricular ejection fraction ≥10% was classified as response to therapy. Control endomyocardial biopsy followed the end of treatment. Twenty-six Myocarditis-NCV patients presented with heart failure; four with electrical instability. Cause of Myocarditis-NCV included infectious agents (10%) and immune-mediated causes (chest trauma 3%; drug hypersensitivity 7%; hypereosinophilic syndrome 3%; primary autoimmune diseases 33%, idiopathic 44%). Abs were positive in immune-mediated Myocarditis-NCV and virus-negative Myocarditis; Myocarditis-NCV patients with Ab+ presented autoreactivity in vessel walls. Toll-like receptor 4 was overexpressed in immune-mediated forms and poorly detectable in viral. Interleukin-1β was significantly higher in Myocarditis-NCV than Myocarditis, the former presenting 24% in-hospital mortality compared with 1.5% of Myocarditis cohort. Immunosuppression induced improvement of cardiac function in 88% of Myocarditis-NCV and 86% of virus-negative Myocarditis patients.

Conclusion
Necrotizing coronary vasculitis is histologically detectable in 1.5% of Myocarditis. Necrotizing coronary vasculitis includes viral and immune-mediated causes. Intra-hospital mortality is 24%. The immunologic pathway is associated with beneficial response to immunosuppression.
A leucopoietic-arterial axis underlying the link between ambient air pollution and cardiovascular disease in humans
Authors: Abohashem Shady , Osborne Michael T , Dar Tawseef , Naddaf Nicki , Abbasi Taimur , Ghoneem Ahmed , Radfar Azar , Patrich Tomas , Oberfeld Blake , Tung Brian , Fayad Zahi A , Rajagopalan Sanjay , Tawakol Ahmed 
Published: November 2020

Abstract

Aims
Air pollution [i.e. particulate matter with diameter &lt;2.5 μm (PM2.5)] is a risk factor for major adverse cardiovascular events (MACE). While PM2.5 promotes leucopoiesis and atherosclerotic inflammation in experimental models, it is unknown whether this occurs in humans. We tested in humans (a) whether PM2.5 associates with higher leucopoietic tissue activity and arterial inflammation (ArtI), (ii) whether these associations persist after accounting for the effects of potential confounders including socioeconomics, traffic noise, and risk factors, and (iii) whether these tissue effects mediate the association between air pollution and MACE.

Methods and results
Individuals (N = 503) without cardiovascular disease (CVD) or active malignancy underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Major adverse cardiovascular event was adjudicated over 5 years of follow-up. Leucopoietic tissue activity (in bone marrow and spleen) as well as ArtI were measured. Annual PM2.5 levels were assessed at each individual’s home address. At baseline, higher PM2.5 associated with increased leucopoietic activity [standardized (95% CI): 0.129 (0.042, 0.215), P = 0.004] as well as ArtI [0.088 (0.006, 0.171), P = 0.036] after adjusting for CVD risk factors. Over a median 4.1 years, 40 individuals experienced MACE. PM2.5 exposure associated with MACE [Cox HR (95% CI): 1.404 (1.135, 1.737), P = 0.002], remaining significant after adjustment for CVD risk factors and other potential confounders. Mediation analysis demonstrated that increased leucopoietic activity and ArtI serially mediate the link between PM2.5 exposure and MACE.

Conclusions
Higher air pollution exposure associates with heightened leucopoietic activity and ArtI and independently predicts MACE through a biological pathway that includes higher leucopoietic activity and ArtI in series.
Interaction among endophytic bacteria, sweet sorghum (Sorghum bicolor) cultivars and chemical nitrogen fertilization
Authors: Heijo Gabriela , Taulé Cecilia , Mareque Cintia , Stefanello Adriano , Souza Emanuel M , Battistoni Federico 
Published: November 2020

ABSTRACT
The application of new agricultural technologies to attain sustainable production systems is necessary. The use of plant growth-promoting bacteria to improve plant growth and health has been studied for decades. This work aimed to isolate diazotrophic endophytic bacteria associated with sweet sorghum plants and study the interaction of their inoculation in combination with chemical N-fertilization on different sorghum cultivars. A bacterial collection of 181 isolates was constructed and characterized in vitro and in vivo. From that, the strains Enterobacter sp. UYSB89 and Kosakonia sp. UYSB139 were nifH+, produce IAA, defined as true endophytes and able to promote growth of two sweet sorghum under greenhouse conditions. The evaluated cultivars responded differentially to bacterial inoculation, the nitrogen fertilization doses and their interaction. Thus, plant growth is a multifactorial consequence of the interrelation between crop practices and the plant genotypes. This knowledge is a valuable factor in terms of understanding plant–bacteria endophyte interactions to preserve environmental sustainability during the implementation of agronomic practices.
Nanopore Amplicon Sequencing Reveals Molecular Convergence and Local Adaptation of Rhodopsin in Great Lakes Salmonids
Authors: Eaton Katherine M , Bernal Moisés A , Backenstose Nathan J C , Yule Daniel L , Krabbenhoft Trevor J 
Published: November 2020

Abstract
Local adaptation can drive diversification of closely related species across environmental gradients and promote convergence of distantly related taxa that experience similar conditions. We examined a potential case of adaptation to novel visual environments in a species flock (Great Lakes salmonids, genus Coregonus) using a new amplicon genotyping protocol on the Oxford Nanopore Flongle and MinION. We sequenced five visual opsin genes for individuals of Coregonus artedi, Coregonus hoyi, Coregonus kiyi, and Coregonus zenithicus. Comparisons revealed species-specific differences in a key spectral tuning amino acid in rhodopsin (Tyr261Phe substitution), suggesting local adaptation of C. kiyi to the blue-shifted depths of Lake Superior. Ancestral state reconstruction demonstrates that parallel evolution and “toggling” at this amino acid residue has occurred several times across the fish tree of life, resulting in identical changes to the visual systems of distantly related taxa across replicated environmental gradients. Our results suggest that ecological differences and local adaptation to distinct visual environments are strong drivers of both evolutionary parallelism and diversification.
Lessons learnt from the field: a qualitative evaluation of adolescent experiences of a universal mental health education program
Authors: Johnson C L , Hart L M , Rossetto A , Morgan A J , Jorm A F 
Published: November 2020

Abstractteen Mental Health First Aid (teenMHFA) is a school-based mental health program that trains adolescents to support peers who are experiencing mental health problems or crises. The program has been evaluated for adolescents aged 15–18 years as part of a randomized controlled trial, however qualitative feedback from students on their perceptions of the program is yet to be explored. The current study describes the perspectives of students who took part in the trial. Feedback on the perceived strengths and weaknesses of the program was provided by 979 Year 10 students (M = 15.82 years, female = 43.94%, English as a first language = 72.77%) at four government funded public schools in Melbourne, Australia via online surveys. A content and thematic analysis was performed on the data using a six-step process. Students generally found the program relevant and they connected with the visual material, personal stories and interactive activities. Suggestions for improvements included encouraging active student participation in classroom discussion and providing opportunities to practice skills. School-based mental health education can benefit from input from stakeholder perspectives, particularly when designing mental health content for delivery by external trainers.
Systematic Review of Design Guidelines for Full-Body Interactive Games
Authors: Subramanian Sruti , Skjæret-Maroni Nina , Dahl Yngve 
Published: November 2020

AbstractThis paper provides a systematic review of research articles published between 2010 and mid-2018 that have offered design guidelines for full-body interactive games for recreational purposes and physical exercise. From an initial 3562 retrieved database references, 22 articles were found to meet our predefined criteria and were included in the final review. The review of 22 articles resulted in the extraction of 107 design guidelines, which were grouped in 12 different categories: movement elicitation, mapping of movement, explicit movement guidance, player representation and game world, attention, feedback on player performance, player agency and customization, exertion, safety, universal design and social aspects. While the current body of guidelines was found to cover multiple aspects pertaining to the design of full-body interactive games, the conducted review also revealed a number of overarching concerns regarding the present state. Specifically, these concerns relate to (i) the hedonic–utilitarian divide in movement-related design guidelines of relevant literature, (ii) the lack of common structure for specifying guidelines, (iii) the lack of systematic development of guidelines, (iv) the issues related to the validity of the existing guidelines and (v) the limited focus on tangible interfaces in the present state of the art. In conclusion, the current review paints a somewhat questionable picture of the present state of the corpus of design guidelines for full-body games, with relatively large differences in the quality of the guidelines proposed in the individual articles and a lack of reference to already existing guidelines. In the longer run, these quality issues risk watering out the original meaning of the term design guideline and reducing the potential value design guidelines can offer in development of full-body interactive games.
Case report: multiple gastrointestinal stroma tumors in the background of neurofibromatosis type 1
Authors: Beck Tim N , Brown Kevin , Lapinski James , Gurajala Ram K , Karamlou Kasra , Augustin Toms 
Published: November 2020

Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies of the gastrointestinal tract. GISTs can occur in the background of neurofibromatosis 1 (NF-1), where chemotherapeutic treatment is not optimal and surgical intervention is the only management option. In this case report, we present a case involving a 61-year-old gentleman with NF-1. The patient presented with acute blood loss anemia that was initially controlled with embolization of a hyper-vascular mass abutting the distal jejunum. The patient was taken to the operating room for excision of the mass. All macroscopic disease was excised and the pathology noted GISTs. Surgical decision making is not clearly delineated in the literature for GISTs in patients with NF-1, where targeted therapy is not a treatment option. Resection of all disease should be considered, since NF-1 associated GISTs generally do not have harbor mutations that can be targeted.