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The rare earth elements (REEs) are critical resources for many clean energy technologies, but are difficult to obtain in their elementally pure forms because of their nearly identical chemical properties. Here, an analogue of macropa, G-macropa, was synthesized and employed for an aqueous precipitation-based separation of Nd 3+ and Dy 3+ . G-macropa maintains the same thermodynamic preference for the large REEs as macropa, but shows smaller thermodynamic stability constants. Molecular dynamics studies demonstrate that the binding affinity differences of these chelators for Nd 3+ and Dy 3+ is a consequence of the presence or absence of an inner-sphere water molecule, which alters the donor strength of the macrocyclic ethers. Leveraging the small REE affinity of G-macropa, we demonstrate that within aqueous solutions of Nd 3+ , Dy 3+ , and G-macropa, the addition of HCO 3 - selectively precipitates Dy 2 (CO 3 ) 3 , leaving the Nd 3+ -G-macropa complex in solution. With this method, remarkably high separation factors of 841 and 741 are achieved for 50 : 50 and 75 : 25 mixtures. Further studies involving Nd 3+ :Dy 3+ ratios of 95 : 5 in authentic magnet waste also afford an efficient separation as well. Lastly, G-macropa is recovered via crystallization with HCl and used for subsequent extractions, demonstrating its good recyclability., (© 2024 Wiley-VCH GmbH.)

The management of patients with atrial fibrillation (AF) requires intricate clinical decision-making to optimize outcomes. In everyday clinical practice, physicians undergo difficult choices to better manage patients with AF. They need to balance thromboembolic and bleeding risk to focus on patients' symptoms and to manage a variety of multiple comorbidities. In this review, we aimed to explore the multifaceted dimensions of clinical decision-making in AF patients, encompassing the definition and diagnosis of clinical AF, stroke risk stratification, oral anticoagulant therapy selection, consideration of bleeding risk, and the ongoing debate between rhythm and rate control strategies. We will also focus on possible grey zones for the management of AF patients. In navigating this intricate landscape, clinicians must reconcile the dynamic interplay of patient-specific factors, evolving guidelines, and emerging therapies. The review underscores the need for personalized, evidence-based clinical decision-making to tailor interventions for optimal outcomes according to specific AF patient profiles.

In the 2000s, cardiac resynchronization therapy (CRT) became a revolutionary treatment for heart failure with reduced left ventricular ejection fraction (HFrEF) and wide QRS. However, about one-third of CRT recipients do not show a favorable response. This review of the current literature aims to better define the concept of CRT response/nonresponse. The diagnosis of CRT nonresponder should be viewed as a continuum, and it cannot rely solely on a single parameter. Moreover, baseline features of some patients might predict an unfavorable response. A strong collaboration between heart failure specialists and electrophysiologists is key to overcoming this challenge with multiple strategies. In the contemporary era, new pacing modalities, such as His-bundle pacing and left bundle branch area pacing, represent a promising alternative to CRT. Observational studies have demonstrated their potential; however, several limitations should be addressed. Large randomized controlled trials are needed to prove their efficacy in HFrEF with electromechanical dyssynchrony., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) may be asymptomatic and the extensive monitoring capabilities of cardiac implantable electronic devices (CIEDs) revealed asymptomatic atrial tachi-arrhythmias of short duration (minutes-hours) occurring in patients with no prior history of AF and without AF detection at a conventional surface ECG. Both the terms "AHRE" (Atrial High-Rate Episodes) and subclinical AF were used in a series of prior studies, that evidenced the association with an increased risk of stroke. Two randomized controlled studies were planned in order to assess the risk-benefit profile of anticoagulation in patients with AHRE/subclinical AF: the NOAH and ARTESiA trials. The results of these two trials (6548 patients enrolled, overall) show that the risk of stroke/systemic embolism associated with AHRE/subclinical AF is in the range of 1-1.2 % per patient-year, but with an important proportion of severe/fatal strokes occurring in non-anticoagulated patients. The apparent discordance between ARTESiA and NOAH results may be approached by considering the related study-level meta-analysis, which highlights a consistent reduction of ischemic stroke with oral anticoagulants vs. aspirin/placebo (relative risk [RR] 0.68, 95 % CI 0.50-0.92). Oral anticoagulation was found to increase major bleeding (RR 1.62, 95 % CI 1.05-2.5), but no difference was found in fatal bleeding (RR 0.79, 95 % CI 0.37-1.69). Additionally, no difference was found in cardiovascular death or all-cause mortality. Taking into account these results, clinical decision-making for patients with AHRE/subclinical AF at risk of stroke, according to CHA 2 DS 2 -VASc, can now be evidence-based, considering the benefits and related risks of oral anticoagulants, to be shared with appropriately informed patients., Competing Interests: Declaration of competing interest The authors report no conflict of interests related to the present article. G Boriani reported small speaker fees from Bayer, Boehringer Ingelheim, Boston, Daiichi Sankyo, Janssen, and Sanofi outside of the submitted work. G Boriani is the Principal Investigator of the ARISTOTELES project (Applying ARtificial Intelligence to define clinical trajectorieS for personalized predicTiOn and early deTEction of comorbidity and muLtimorbidity pattErnS) that received funding from the European Union within the Horizon 2020 Research and Innovation Program (Grant N. 101080189). M Proietti is the Italian national leader of the AFFIRMO project on multimorbidity in atrial fibrillation, that received funding from the European Union within the Horizon 2020 Research and Innovation Program (Grant N. 899871). The other authors did not report conflicts of interest to disclose outside of the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified., Methods: In a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF., Results: A total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %). After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both)., Conclusions: In a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %., Competing Interests: Declaration of Competing Interest The authors reported no conflict of interests related to the present article. GB reported small speaker fees from Bayer, Boehringer Ingelheim, Boston, Daiichi Sankyo, Janssen, and Sanofi. GFR reported consultancy for Boehringer Ingelheim and an educational grant from Anthos, outside the submitted work. (no fees are directly received personally). MP is national leader of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 899871; TP reported to be consultant for Bayer and Pfizer (no fees). GAD reported small speaker fees from Boehringer-Ingelheim, Pfizer, Bayer, Sanofi; GYHL reported to be consultant and speaker for Bayer/Janssen, BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo (no fees are directly received personally). All the disclosures occurred outside the submitted work. Other authors have no disclosures to declare, (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest GB: small speaker fee from Bayer, Boston, Boehringer Ingelheim, Daiichi Sankyo, Janssen and Sanofi. All the disclosures occurred outside the submitted work. Other authors have no disclosures to declare

Aims: To know the prevalence of atrial fibrillation (AF), as well as the incidence of postoperative AF (POAF) in vascular surgery for arterial diseases and its outcome implications., Methods: We performed a systematic review and meta-analysis following the PRISMA statement., Results: After the selection process, we analyzed 44 records (30 for the prevalence of AF history and 14 for the incidence of POAF).The prevalence of history of AF was 11.5% [95% confidence interval (CI) 1-13.3] with high heterogeneity (I2 = 100%). Prevalence was higher in the case of endovascular procedures. History of AF was associated with a worse outcome in terms of in-hospital death [odds ratio (OR) 3.29; 95% CI 2.66-4.06; P < 0.0001; I2 94%] or stroke (OR 1.61; 95% CI 1.39-1.86; P < 0.0001; I2 91%).The pooled incidence of POAF was 3.6% (95% CI 2-6.4) with high heterogeneity (I2 = 100%). POAF risk was associated with older age (mean difference 4.67 years, 95% CI 2.38-6.96; P = 0.00007). The risk of POAF was lower in patients treated with endovascular procedures as compared with an open surgical procedure (OR 0.35; 95% CI 0.13-0.91; P = 0.03; I2 = 61%)., Conclusions: In the setting of vascular surgery for arterial diseases a history of AF is found overall in 11.5% of patients, more frequently in the case of endovascular procedures, and is associated with worse outcomes in terms of short-term mortality and stroke.The incidence of POAF is overall 3.6%, and is lower in patients treated with an endovascular procedure as compared with open surgery procedures. The need for oral anticoagulants for preventing AF-related stroke should be evaluated with randomized clinical trials., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA ( n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43-67.79%), mean values for MCF were significantly reduced in HCM-48.55% (43.46-54.86% p < 0.001)-and CA-40.92% (36.68-46.84% p < 0.002)-but not in IH-59.35% (53.22-64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R 2 = 0.136) and the four study subgroups (healthy adults, R 2 = 0.039 IH, R 2 = 0.089; HCM, R 2 = 0.225; CA, R 2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients.

The mutation space of spatially conserved (MSSC) amino acid residues is a protein structural quantity developed and described in this work. The MSSC quantifies how many mutations and which different mutations, i.e., the mutation space, occur in each amino acid site in a protein. The MSSC calculates the mutation space of amino acids in a target protein from the spatially conserved residues in a group of multiple protein structures. Spatially conserved amino acid residues are identified based on their relative positions in the protein structure. The MSSC examines each residue in a target protein, compares it to the residues present in the same relative position in other protein structures, and uses physicochemical criteria of mutations found in each conserved spatial site to quantify the mutation space of each amino acid in the target protein. The MSSC is analogous to scoring each site in a multiple sequence alignment but in three-dimensional space considering the spatial location of residues instead of solely the order in which they appear in a protein sequence. MSSC analysis was performed on example cases, and it reproduces the well-known observation that, regardless of secondary structure, solvent-exposed residues are more likely to be mutated than internal ones. The MSSC code is available on GitHub: "https://github.com/Cantu-Research-Group/Mutation&#95;Space"., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: The incidence of infections and death in patients implanted with cardiac implantable electronic devices (CIEDs) is not fully known yet., Aim: To describe the incidence of CIED-related infection and death, and their potential predictors in a contemporary cohort of CIED patients., Methods: All consecutive patients implanted with a CIED at our institution were prospectively enrolled. Follow-up visits were performed 2 weeks after CIED implantation for all patients, and then every 6 months for implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT) patients and every 12 months for pacemaker (PM) patients. The adjudication of CIED-related infections was performed by two independent investigators and potential disagreement was resolved by a senior investigator., Results: Between September 2016 and August 2020, a total of 838 patients were enrolled (34.6% female; median age 77 (69.6-83.6); median PADIT score 2 (2-4)). PMs were implanted in 569 (68%) patients and ICD/CRT in 269 (32%) patients. All patients had pre-implant antibiotic prophylaxis and 5.5% had an antibiotic-eluting envelope. Follow-up data were available for 832 (99.2%) patients. After a median follow-up of 42.3 (30.2-56.4) months, five (0.6%) patients had a CIED-related infection and 212 (25.5%) patients died. Using multivariate Cox regression analysis, end-stage chronic kidney disease (CKD) requiring dialysis and therapy with corticosteroids was independently associated with a higher risk of infection (hazard ratio (HR): 14.20; 95% confidence interval (CI) 1.48-136.62 and HR: 14.71; 95% CI 1.53-141.53, respectively). Age (HR: 1.07; 95% CI 1.05-1.09), end-stage CKD requiring dialysis (HR: 6.13; 95% CI 3.38-11.13) and history of atrial fibrillation (HR: 1.47; 95% CI 1.12-1.94) were independently associated with all-cause death., Conclusions: In a contemporary cohort of CIED patients, mortality was substantially high and associated with clinical factors depicting a population at risk. On the other hand, the incidence of CIED-related infections was low.

Introduction: VDD pacing system was introduced more than 30 years ago. Its use is considered by the 2021 European Society of Cardiology guidelines on cardiac pacing as a potential alternative to dual chambers system for patients with atrioventricular block and normal sinus node function., Areas Covered: In this article, we performed a narrative review of current literature in order to identify the strengths and weaknesses of this pacing system. VDD system allows the maintenance of AV synchronous pacing and its hemodynamic advantages. Some disadvantages may be related to the non-negligible incidence of atrial undersensing and the possible subsequent need for upgrade to DDD system. On the other hand, shorter implantation time and lower complications rate may be advantages., Expert Opinion: In the modern pacing era, VDD pacing system struggles to find its own space. However, it may still be considered as a valuable alternative to a dual-chamber pacemaker for selected patients, in specific clinical scenarios.

Background: Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) may be associated with a risk of progression towards long-lasting episodes (≥24 h) and clinical atrial fibrillation (AF)., Methods: Consecutive CIED patients presenting AHRE (with confirmation of an arrhythmia lasting 5 min-23 h 59 min, atrial rate ≥175/min, with no AF at 12-lead ECG and no prior clinical AF) were retrospectively enrolled. The aims of this study were to describe patients' characteristics and the incidence of adverse events, and second, to identify potential predictors of the composite outcome of clinical AF and/or AHRE episodes lasting ≥24 h., Results: 104/107 (97.2%) patients (median age 79.7 (74.0-84.2), 33.7% female) had available follow-up data. Over a median follow-up of 24.3 (10.6-40.3) months, 31/104 (29.8%) patients experienced the composite outcome of clinical AF or AHRE episodes lasting ≥24 h. Baseline CHA 2 DS 2 -VASc score and the longest AHRE episode at enrollment lasting 12 h-23 h 59 min were independently associated with the composite outcome (Hazard ratio (HR); 95% CI: 1.40; 1.07-1.83 and HR: 8.15; 95% CI 2.32-28.65, respectively). Baseline CHA 2 DS 2 -VASc score and the longest AHRE episode at enrollment lasting 12 h-23 h 59 min were the only independent predictors of incident clinical AF (HR: 1.45; 95% CI 1.06-2.00 and HR: 4.25; 95% CI 1.05-17.20, respectively)., Conclusions: In patients with AHRE, the incidence of clinical AF or AHRE episodes lasting ≥24 h is high in a two-year follow-up. Baseline patients' characteristics (CHA 2 DS 2 -VASc score) and AHRE duration may help to intensify monitoring and decision-making, being independently associated with clinical AF at follow-up.

Acute Kidney Injury (AKI) is an important issue for the healthcare system, as it is associated with high mortality and increased risk of readmission, with consequent elevated healthcare resource utilization. We investigated the incidence of AKI based on the examination of the discharge cards of all patients admitted between January 1 2011 and December 31 2015 at the Parma University Hospital, as well as the frequency and type of 30-day hospital readmission in the patients discharged with a first AKI diagnosis (index admission). The mean pooled 5-year incidence of AKI was 2.4%. The mean frequency of 30-day readmission for any disease in patients discharged with a first AKI diagnosis in the selected time interval was 23.1%/year. The main four disease categories, as assessed by the Diagnosis Related Group (DRG) classification, responsible for patient 30-day readmission were a new AKI episode, heart failure, respiratory failure requiring or not requiring mechanical ventilation, and sepsis. The mean lenght of hospital stay of patients discharged with AKI as a principal or secondary diagnosis was 14.4 and 21.8 days, respectively. Based on the evaluation of administrative data from all hospital admissions at the Parma University Hospital in the 2011-2015 5-year period, we conclude that AKI represents a serious challenge for the healthcare system, with high short-term morbidity and increased resource utilization due to frequent hospital readmissions., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

The zinc-specific fluorophore, Zinpyr-1, is used in competition assays to determine the kinetic and thermodynamic parameters of Zn2+ binding to engineered bi-histidine sites located in ubiquitin and the B domain of protein A (BdpA). These binding sites are used in psi analysis studies to investigate structure formation in the folding transition state identified by the change in folding rate upon addition of metal ions. For ubiquitin, the on-rate binding constant and binding affinity for a site located along an alpha-helix are measured to be approximately 10(7) M-1 s-1 and 3 microM, respectively. For a site located across two beta-strands, the metal binding affinity was too weak to measure in the dye competition assays (Kd > 55 microM). The equilibrium-determined values for the Zn2+-induced stabilization of ubiquitin and BdpA match the values derived from changes in the global folding and unfolding rates. Therefore, metal ion binding is in fast equilibrium during the transit over the free energy barrier. Accordingly, the folding rate must be slower than the product of the fractional population of a high-energy intermediate with the metal site formed and the metal binding on-rate constant. The known folding rate of 20 s-1 at 1.5 M guanidinium chloride in 400 microM Zn2+ provides an upper bound for the stability of such intermediates (DeltaG(U-I) < 4 kcal/mol). These results support a view of the apparent two-state protein folding reaction surface as a fast pre-equilibrium between the denatured state and a series of high-energy species. The net folding rate is a product of the equilibrium constant of the highest-energy species and a transmission rate. For ubiquitin, we estimate the transmission rate to be approximately 10(4) s-1. Implications for the role of unfolded chain diffusion on folding rates and barrier heights are discussed.