bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial fibrillation in heart failure: drugs or ablation?
Authors: Palmas Francesco , Noviello Cecilia , Bo Mario 
Published: April 2023

Abstract
Atrial fibrillation (AF) and heart failure (HF) frequently coexist and mutually exert negative influences with important clinical implications. Although there is evidence that restoring and maintaining sinus rhythm may have favourable clinical effects in patients with HF, there is no evidence of a survival benefit with pharmacological antiarrhythmic intervention compared with a heart rate control strategy. In these patients, transcatheter ablation (CA) of AF represents a procedure with an excellent safety profile in centres with expertise and a high volume of interventions. However, in the absence of definite evidence of benefit on major clinical end-points that can be generalized to the heterogeneous population with AF and HF, the option of CA should be discussed and shared with the patient, and mainly considered in patients with conditions that are associated with a greater prospect of clinical benefit, such as ‘young’ age (65–70 years), good health conditions and few or no comorbidities, recent onset of HF and AF (especially if with high heart rate), left atrial volume not excessively compromised (&lt;55 mm in diameter), and without evidence of substantial fibrotic remodelling, left ventricular ejection fraction (LVEF) &gt;25%, including HF with preserved EF (HFpEF).
Hypocholesterolaemic treatment in coronary unit: from statins to anti PCSK9 therapies and bempedoic acid
Authors: Ferri Nicola , Corsini Alberto , Ruscica Massimiliano 
Published: April 2023

Abstract
The knowledge that roughly 20% of survivors from an acute coronary syndrome (ACS) event experience a subsequent ischaemic cardiovascular event within 24 months with a 5-year mortality range between 19 and 22% highlights the importance of the lipid-lowering strategies in the secondary prevention after ACS. In this framework, statin treatment significantly improves clinical outcome after ACS. Within this remit, in the present review we critically discuss the use of statin and non-statin lipid-lowering approaches (ezetimibe, evolocumab, alirocumab, inclisiran, and bempedoic acid) in the early management of ACS patients. Relative to this latter aspect, the knowledge that circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are raised during ACS could be a generating hypothesis justifying the use of PCSK9 inhibitors in ACS. Thus, in a field fraught of uncertainty, the main barrier to the widespread prescription of non-statin agents (e.g. PCSK9 inhibitors) relates to their costs when compared with other lipid-lowering agents (e.g. statins and ezetimibe).
Renal denervation and long-term results
Authors: Simonetti Fiorenzo , Piccolo Raffaele , Esposito Giovanni 
Published: April 2023

Abstract
Arterial hypertension is a condition with a high prevalence in the global population and represents a major risk factor for adverse cardiovascular events, including stroke and death. Non-pharmacological and pharmacological interventions, with combination therapy as a standard strategy, are very effective in achieving optimal blood pressure (BP) goals. Nevertheless, in a non-negligible proportion of patients, drug therapy is ineffective at achieving BP targets or there is intolerance to specific anti-hypertensive medications. In this context, the use of invasive treatments for BP control, including renal denervation, represents a valuable therapeutic option. Renal denervation has experienced ups and downs over the years, with an initial growth period and a decline mainly linked to the initial negative results of a large, randomized trial. However, recent data from new trials and long-term follow-up of initial trials have confirmed the benefit and safety of the procedure by relaunching it in daily clinical practice. Additional research evaluating ablation methods other than radiofrequency are needed to be able to more clearly define the role of this procedure and the type of patients that can benefit most from it.
Sudden death in ischemic heart disease: looking for new predictors: polygenic risk
Authors: Boccanelli Alessandro , Scardovi Angela Beatrice 
Published: April 2023

Abstract
The phenomenon of sudden death (SD) occurs, in 70% of cases, in people who do not fall within the indications of the guidelines relating to the implantation of the defibrillator. There is a way of inheriting the risk condition by genetic means, the polygenic one, in which mutations are not found, but an increase in alleles of common variations called polymorphisms. The PRE-DETERMINE cohort study has the primary objective of determining whether biological markers, and electrocardiogram can be used to identify individuals more likely to experience SD. Within the study, we investigated the utility of the genome-wide polygenic score for coronary artery disease (GPSCAD) for SD risk stratification in an intermediate-risk population with stable coronary artery disease without severe systolic dysfunction and/or indication for an implantable cardioverter defibrillator in primary prevention. Over a mean follow-up period of 8.0 years, patients in the top decile of GPSCAD were at higher absolute (8.0% vs. 4.8%; P &lt; 0.005) and relative (29% vs. 16%; P &lt; 0.0003) risk of SD compared to the rest of the cohort. No association was found between the highest decile of GPSCAD and other forms of death, cardiac, and non-cardiac. The data on the increase in absolute and relative terms of SD can be used, at this stage, only for a theoretical estimate on the possible efficacy of the defibrillator in the population with chronic coronary artery disease and moderately depressed left ventricular function as number needed to treat and possible reduction of mortality in high-risk patients (those included in the top decile of GPSCAD).
Less sodium and more potassium to reduce cardiovascular risk
Authors: Muiesan Maria Lorenza , Buso Giacomo , Agabiti Rosei Claudia 
Published: April 2023

Abstract
An increase in the dietary consumption of salt is associated with a progressive increase in blood pressure (BP) values, and with an increase in the incidence of cardiovascular disease. Reducing the dietary intake of sodium in the population is a public health goal in many countries around the world. Numerous studies have described a linear relationship between high dietary salt intake and the development of arterial hypertension, as well as a negative association between high potassium intake and BP values. Furthermore, there is evidence that a reduction in salt consumption and an increase in potassium consumption can be associated with a decrease in BP values, improving the general state of health. Therefore, it would be desirable to further improve awareness of the risks associated with an excessive intake of salt and low potassium by maintaining public education campaigns and trying to overcome the numerous obstacles to a process of greater responsibility for people regarding nutrition.
Arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy
Authors: Del Mestre Eva , Pio Loco Detto Gava Carola , Paldino Alessia , Gigli Marta , Rossi Maddalena , Lalario Andrea , Dal Ferro Matteo , Merlo Marco , Sinagra Gianfranco 
Published: April 2023

Abstract
Dilated cardiomyopathy is a primary disease of the heart muscle, which affects relatively young patients with a low comorbidity profile. It is characterized by structural and/or functional abnormalities leading to systolic dysfunction of the left ventricle or of both ventricles, often associated with dilatation, in the absence of an ischaemic, valvular, or pressure overload cause sufficient to explain the phenotype. Although the prognosis of the disease has greatly improved over the last few decades, prognostic stratification remains a fundamental objective, especially about the prediction of potentially life-threatening arrhythmic events. An accurate diagnostic work-up and an appropriate aetiopathogenetic characterization affect the patients’ outcome and represent the essential basis of an adequate prognostic stratification. It is necessary to adopt a multiparametric approach, especially when the aim is the prediction of arrhythmic risk; it includes an integration of medical history and physical examination with cardiac imaging and genetic testing, in order to obtain a personalized diagnosis and therapeutic strategies. Furthermore, the evaluation should be repeated at every clinical check-up, considering the dynamic trend of the pathology and the arrhythmic risk changes over time. This article aims to illustrate how, starting from an exhaustive aetiological and clinical–instrumental characterization, including all diagnostic methods available at present time, it is possible to obtain a tailored diagnostic evaluation and stratification of the arrhythmic risk as accurate as possible.
Challenges in cardiology: diagnosis of native and prosthetic valve endocarditis
Authors: Pepi Mauro , Muratori Manuele 
Published: April 2023

Abstract
New cardiovascular imaging technologies have strongly influenced the diagnosis of bacterial endocarditis [infective endocarditis (IE)]. The clinical presentation of IE is polymorphic, which explains the difficulty of diagnosis and the delay in treatment. Symptoms such as fever, chills, loss of appetite and weight, and embolic phenomena strongly support the diagnosis of endocarditis, but are not always present, particularly in elderly or immuno-compromised patients. Moreover, subtle symptoms in patients at high risk for the development of IE, such as those with prosthetic valves or intracardiac devices, patients with congenital heart disease, and drug addicts should lead to the suspicion that a diagnosis of IE is highly probable. In this review, we will focus on the diagnosis of complex IE in native valves and prosthetic valves.
Sudden cardiac death in ischaemic heart disease: coronary thrombosis or myocardial fibrosis?
Authors: Prati Francesco , Gurguglione Giovanni , Biccire Flavio , Cipolloni Luigi , Ferrari Michela , Di Toro Alessandro , Arbustini Eloisa 
Published: April 2023

Abstract
The mechanisms underlying sudden cardiac death (SCD) in patients with ischaemic heart disease (IHD) caused by coronary atherosclerosis are not yet clarified. For decades, acute coronary causes have been sought as the main triggers of SCD in these patients. In fact, angiographic and pathological studies in cardiac arrest survivors and SCD victims, respectively, consistently show that acute plaque events occur in ∼50% of SCD of patients with IHD. Among the acute events, plaque rupture and erosion triggering acute coronary thrombosis remain the main substrates; however, a significant percentage of plaque haemorrhage (20%) is identified by pathological studies. Its role in acute coronary thrombosis is unknown and deserves future intravascular imaging developments. In the remaining 50% of SCD, the atherosclerotic coronary disease shows the characteristics of structural stability. More recent studies have focused attention not only on the coronary tree and on the search for acute complications of atherosclerotic plaques but also on myocardial tissue, identifying replacement and patchy fibrosis as the most frequent findings in the post-mortem hearts of these patients, a feature followed by cardiac hypertrophy, as assessed by the heart weight, usually associated with fibrosis. The possibility of characterizing myocardial fibrosis in vivo, besides confirming the pathological data, now offers new risk stratification perspectives to prevent SCD in IHD, alongside the consolidated secondary prevention criteria based on left ventricular dysfunction.
Nightmare in the ward: difficult Clostridioides infection
Authors: Tarasi Agapito 
Published: April 2023

Abstract
Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacillus. It is isolated in 80% of the stools of children and infants and in 3% of healthy adults. It causes gastrointestinal tract infections and affects patients who make prolonged use of antibiotics. It causes C. difficile colitis with symptoms ranging from diarrhoea to pseudomembranous colitis to toxic megacolon. The main virulence factors of C. difficile are toxin A, toxin B, and binary toxin. It is one of the most common nosocomial infections but in recent years, however, many infections have also been found at the community level. They are associated not only with a high risk of mortality but also with a prolongation of hospital stay. One of the critical aspects of C. difficile infections is also represented by the high frequency of relapses. Consequently, the economic impact is significant. Specific situations constitute risk factors for infection, such as exposure to antibiotic therapy in the previous months, in particular fluoroquinolones, third-generation cephalosporins, clindamycin, repeated hospitalizations in healthcare facilities, including long-term care, as well as the patient’s clinical conditions such as comorbidities, age &gt;65, chemotherapy and immunosuppressive treatments, recent surgery of any type, and pump inhibitor therapy. Treatment protocols will be described in the paper.
Copy number variation of gasdermin D gene is associated with atrial fibrillation-related thromboembolic stroke
Authors: Huang Pang-Shuo , Cheng Jen-Fang , Li Guan-Wei , Chuang Eric Y , Chen Jien-Jiun , Chiu Fu-Chun , Wu Cho-Kai , Wang Yi-Chih , Hwang Juey-Jen , Tsai Chia-Ti 
Published: April 2023

Abstract

Aims
Atrial fibrillation (AF) is one of the major causes of ischaemic stroke. In addition to clinical risk evaluated by the CHA2DS2-VASC score, the impact of genetic factors on the risk of AF-related thromboembolic stroke has been largely unknown. We found several copy number variations (CNVs) in novel genes that were associated with thromboembolic stroke risk in our AF patients by genome-wide approach. Among them, the gasdermin D (GSDMD) gene was related to inflammation. We aimed to test whether GSDMD deletion was associated with AF-related stroke.

Methods and results
A total of 400 patients with documented non-familial AF were selected, of which 100 patients were diagnosed with ischaemic stroke. The baseline characteristics of age, sex, valvular heart disease, coronary artery disease, heart failure, and CHA2DS2-VASc scores were not statistically different between cases and controls. We found that individuals who carried GSDMD homozygous deletion genotype had a higher risk for ischaemic stroke (odds ratio 2.195; 95% confidence interval, 1.24–3.90; P = 0.007), even adjusted by CHA2DS2-VASc scores. We also validated the association of GSDMD with AF stroke in a large Caucasian population (UK Biobank).

Conclusion
We found a link between the homozygous deletion of the GSDMD gene and an increased risk of stroke in patients with AF. This may implicate the use of therapy targeting GSDMD in the prevention of ischaemic stroke for AF patients.
Parallel shifts in trout feeding morphology suggest rapid adaptation to alpine lake environments
Authors: Combrink Lucia L , Rosenthal William C , Boyle Lindsey J , Rick Jessica A , Mandeville Elizabeth G , Krist Amy C , Walters Annika W , Wagner Catherine E 
Published: April 2023

Abstract
Eco-evolutionary interactions following ecosystem change provide critical insight into the ability of organisms to adapt to shifting resource landscapes. Here we explore evidence for the rapid parallel evolution of trout feeding morphology following eco-evolutionary interactions with zooplankton in alpine lakes stocked at different points in time in the Wind River Range (Wyoming, USA). In this system, trout predation has altered the zooplankton species community and driven a decrease in average zooplankton size. In some lakes that were stocked decades ago, we find shifts in gill raker traits consistent with the hypothesis that trout have rapidly adapted to exploit available smaller-bodied zooplankton more effectively. We explore this morphological response in multiple lake populations across two species of trout (cutthroat trout, Oncorhynchus clarkii, and golden trout Oncorhynchus aguabonita) and examine the impact of resource availability on morphological variation in gill raker number among lakes. Furthermore, we present genetic data to provide evidence that historically stocked cutthroat trout populations likely derive from multiple population sources, and incorporate variation from genomic relatedness in our exploration of environmental predictors of feeding morphology. These findings describe rapid adaptation and eco-evolutionary interactions in trout and document an evolutionary response to novel, contemporary ecosystem change.
Expression of retrotransposons contributes to aging in Drosophila
Authors: Schneider Blair K , Sun Shixiang , Lee Moonsook , Li Wenge , Skvir Nicholas , Neretti Nicola , Vijg Jan , Secombe Julie 
Published: April 2023

Abstract
Retrotransposons are a class of transposable elements capable of self-replication and insertion into new genomic locations. Across species, the mobilization of retrotransposons in somatic cells has been suggested to contribute to the cell and tissue functional decline that occurs during aging. Retrotransposons are broadly expressed across cell types, and de novo insertions have been observed to correlate with tumorigenesis. However, the extent to which new retrotransposon insertions occur during normal aging and their effect on cellular and animal function remains understudied. Here, we use a single nucleus whole genome sequencing approach in Drosophila to directly test whether transposon insertions increase with age in somatic cells. Analyses of nuclei from thoraces and indirect flight muscles using a newly developed pipeline, Retrofind, revealed no significant increase in the number of transposon insertions with age. Despite this, reducing the expression of two different retrotransposons, 412 and Roo, extended lifespan, but did not alter indicators of health such as stress resistance. This suggests a key role for transposon expression and not insertion in regulating longevity. Transcriptomic analyses revealed similar changes to gene expression in 412 and Roo knockdown flies and highlighted changes to genes involved in proteolysis and immune function as potential contributors to the observed changes in longevity. Combined, our data show a clear link between retrotransposon expression and aging.
Palaeomagnetic evidence of the deformation of the Pontides during the closure of the Intra-Pontide Ocean in the early Cretaceous
Authors: Cengiz Mualla 
Published: April 2023

SUMMARY
Several models exist concerning the deformation history of the Pontides in North Anatolia during the Cretaceous period, which vary depending on the positions of the Istanbul and Sakarya zones, the consumption of the northern branches of the Neotethys ocean and the rifting of several sub-basins. Notably, the early Cretaceous tectonic history of the Pontides involved the closure of the northern Neotethys ocean (Intra-Pontide ocean), and the collision between the Istanbul and Sakarya zones, producing thrust structures along the collisional front. The lack of palaeomagnetic data providing evidence for this deformation pattern demonstrates that further investigation is required, particularly focusing on the Lower Cretaceous strata in the Pontides. Thus, this study aimed to examine samples from a total of 78 sites from the Lower–Upper Cretaceous sedimentary rocks, and Middle Eocene to Middle Miocene sedimentary and volcanic rocks. Results of this study indicated large counterclockwise rotations up to R±ΔR = −73.9°±9.1°, and small clockwise rotations of R±ΔR = 14.2°±12.2° in the Istanbul and Sakarya zones, during the Early Cretaceous and Late Cretaceous periods. These rotation patterns are accompanied by the closure of the Intra-Pontide ocean, and the collision between the Istanbul and Sakarya zones during the Early and Late Cretaceous periods. On the other hand, in the Middle Eocene, small counterclockwise rotations of R±ΔR = −6.4°±13.9° and 4.6°±12.9° along the western coastline of the Pontides indicated that the northern margin of the Pontides was stable during this period.
Fibronectin on target cells attenuates natural cytotoxicity of NK cells via myeloid immune checkpoint ILT3/LILRB4/gp49B
Authors: Itagaki Fumika , Nakatsuka Keita , Sakai Haruka , Endo Shota , Su Mei-Tzu , Takai Toshiyuki 
Published: April 2023

Abstract
Natural killer (NK) cells play pivotal roles in innate immunity as well as in anti-tumor responses via natural killing, while their activity is tightly regulated by cell-surface inhibitory receptors. Immunoglobulin-like transcript 3/leukocyte immunoglobulin-like receptor B4 (ILT3/LILRB4, also known as gp49B in mice) is an inhibitory receptor expressed on activated NK cells as well as myeloid-lineage cells. The common physiologic ligand of human LILRB4 and gp49B was identified very recently as fibronectin, particularly the N-terminal 30 kDa domain (FN30). We hypothesized that LILRB4 could bind fibronectin on target cells in trans together with integrins, classical fibronectin receptors, in cis and deliver an inhibitory signal in NK cells, leading to attenuated natural killing. Flow cytometric and confocal microscopic analyses of NK cell-surface gp49B and integrins suggested that these novel and classical fibronectin receptors, respectively, co-engage fibronectin immobilized on a culture plate. Biochemical analyses indicated that tyrosine phosphorylation of spleen tyrosine kinase was augmented in gp49B-deficient NK cells upon binding to the immobilized fibronectin. While surface fibronectin-poor YAC-1 cells were evenly sensitive as to natural killing of both gp49B-positive and -negative NK cells, the killing of fibronectin-rich Lewis lung carcinoma cells, but not the FN30-knockout cells, was augmented among gp49B-deficient NK cells. These results suggest that the natural cytotoxicity of NK cells is negatively regulated through LILRB4/gp49B sensing fibronectin on target cells, which sheds light on the unexpected role of LILRB4 and fibronectin as a potential attenuator of NK cell cytotoxicity in the tumor microenvironment.
Impacts of Bacillus subtilis var. natto on the lifespan and stress resistance of Caenorhabditis elegans
Authors: Teramoto Nao , Sato Kanae , Wada Takayuki , Nishikawa Yoshikazu , Kage-Nakadai Eriko 
Published: April 2023

Abstract

Aim
Bacillus subtilis var. natto is used in the production of natto, a typical Japanese fermented soybean food. Although the probiotic attributes and health-related effects of B. subtilis var. natto have been reported, the effect on longevity remains unknown. In the present study, the effects of B. subtilis var. natto strains on lifespan extension and the molecular mechanisms governing the prolongevity were examined using Caenorhabditis elegans as a model animal.

Methods and results
Synchronized 3-day-old (young adult) worms were fed Escherichia coli OP50 (control) or a subcloned isolate of B. subtilis var. natto Miyagino strain (MI-OMU01) and subjected to lifespan, survival against pathogens and abiotic stress resistance assays. Notably, the lifespan of worms fed MI-OMU01 was significantly longer than that of the animals fed OP50. Moreover, MI-OMU01 increased the resistance of C. elegans to several stressors, including UV irradiation, H2O2, and Cu2+.

Conclusions
Genetic and gene expression analyses using mutant animals suggested that MI-OMU01 extended the lifespan of worms in TIR-1/SARM, p38 MAPK, and insulin/IGF-1 signaling pathway-dependent manners.