Synthesis, Conformational Analysis, Antioxidant and Enzyme Inhibition Activity, Molecular Docking, and DFT Studies of New Chiral Hydrazide–Hydrazone Derivatives

ABSTRACT A new series of chiral hydrazide‐hydrazone derivatives were synthesized and evaluated their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase and urease inhibition and antioxidant activities. The chemical structures of newly synthesized chiral aryl hydrazide‐hydrazone derivatives were clarified using UV–Vis, IR, 1 H and 13 C NMR, and mass spectroscopies. According to NMR data, due to the partial double bond character of the amide C‐N bond, two conformational isomers ( E and Z ) exist in solution. Based on this information, the conformational properties of the synthesized compounds were investigated using temperature‐dependent NMR spectroscopy and DFT. The results of DFT studies revealed that E (C=N) ‐ E (C(O)‐N) conformer is the most stable structure for the synthesized hydrazones. In addition, the enzyme inhibition potentials of the synthesized compounds were evaluated. Among all chiral hydrazide‐hydrazones, compound 3b (containing nitro group in the hydrazone part) had the best inhibition profile against AChE, whereas compound 3d was found to be the most active compound against BChE. In addition, compound 3d , which carries a methoxy group in both the benzamide and the hydrazone moiety, attracted attention due to its good activity against all examined enzymes. Furthermore, molecular docking calculations were performed to get insights into the interaction patterns between the synthesized compounds and the selected target protein.

Effective approach to assess higher heating value of biomass from ultimate and proximate analysis

Abstract For proper design and operation of biomass‐based energy systems, it is important to determine the higher heating value (HHV) of biomass. In this paper, two machine learning (ML) approaches, namely extra trees (ET) and least squares support vector machine (LSSVM), are used to predict the value of HHV associated with biofuels. The data required for HHV calculation, including proximate and ultimate analyses datasets, were collected from the literature. The performances of these two ML approaches for predicting biomass HHV were then compared with other smart models available in the literature. Even though the available empirical models can predict the biomass HHV with acceptable precision, it was found that our proposed ML techniques have a superior performance based on the error analysis; the proposed approaches also consider all key biomass characteristics in the developed models. In addition, the ET model proved to be slightly more accurate compared to the LSSVM model. Additionally, the developed proximate‐based ET model showed better performance compared to the ultimate‐based ET model. The most influential parameters in the developed ET models for the proximate and ultimate approaches were determined to be ash fraction and carbon fraction, respectively. Finally, it was concluded that the smart modelling techniques can be utilized as a robust and reliable alternative predictive methodology to replace direct laboratory measurement of the biomass HHV.

Potassium sulphate production from an aqueous sodium sulphate from lead‐acid battery recycling: Impact of feedstock impurities on products yields

Abstract The increasing demand for renewable energy highlights the need for efficient energy storage solutions. Despite various available technologies, lead‐acid batteries remain preferred for many industrial applications due to their inherent advantages. However, their expanded use necessitates proper waste management and recycling practices. During lead‐acid battery recycling, Na₂SO₄ is generated as a waste product, which cannot be directly sold due to quality concerns and limited market demand. Consequently, advanced waste management techniques are required to comply with government regulations on industrial waste disposal. Despite these challenges, Na 2 SO 4 serves as a vital precursor for producing K 2 SO 4 , a valuable fertilizer. Prior research on the glaserite process for converting Na 2 SO 4 to K 2 SO 4 has assumed Na 2 SO 4 to be pure—without traces of impurities. However, Na 2 SO 4 recovered from battery recycling contains various contaminants. To address this, HSC Chemistry software was used to model K 2 SO 4 and NaCl production from impure Na 2 SO 4 and KCl, considering feed impurities. Under ideal conditions—a 1 bar pressure, 25°C feed temperature, and 40°C reactor temperature—over 90% yield of K 2 SO 4 and NaCl was achieved in the absence of impurities. However, the addition of impurities resulted in a reduction in yields. Notably, impurity levels ranging from 1% to 4% by weight still allowed for yields exceeding 90%. Furthermore, a review of reactor compositions revealed a significant depletion of potassium and chlorine ions which are crucial for K 2 SO 4 and NaCl production as impurity levels varied from 0% to 10%. These findings emphasize the negative impact of impurities on K 2 SO 4 and NaCl yields.

Incidence and Predictors of Clinical Outcomes in Real‐Life Patients With Atrial Fibrillation Treated With Oral Factor Xa Inhibitors: The Follow‐Up Results of the ANATOLIA‐AF Study

ABSTRACT Objective The main objective of this study is to determine the incidence and predictors of clinical outcomes in patients with AF treated with factor Xa inhibitors in a real‐world setting. Methods The present study was a multicentre and observational study that included patients with AF who were treated with factor Xa inhibitors. The primary outcome was the composite of ischemic stroke, TIA, systemic embolism, major bleeding, and all‐cause mortality. Results A total of 1162 patients from 26 cardiology centers were included in this study, with a median age of 72 years. During the median 12‐month follow‐up period, the primary outcome occurred in 195 patients (16.8%). Treatment with rivaroxaban compared with apixaban and edoxaban showed a lower rate of ischemic stroke, TIA, and/or systemic embolism (2.2% vs. 4.7% vs. 6.5%, respectively, p  = 0.014). The major bleeding rate was similar between all three factor Xa inhibitors. The all‐cause mortality rate in the rivaroxaban group was lower compared with the apixaban and edoxaban groups (9.8% vs. 15.1% vs. 12.4%, respectively, p  = 0.042). Overall, the frequency of primary outcome was 13.8%, 19.6%, and 20.6% for patients treated with rivaroxaban, apixaban, and edoxaban, respectively ( p  = 0.019). Older age, male sex, low body weight, high bleeding risk, heart failure, hypertension, liver failure, and treatment with apixaban 2.5 mg b.i.d. were independently associated with the development of primary outcome. Conclusion The follow‐up data from the ANATOLIA‐AF study provides detailed data about the incidence and independent predictors of adverse clinical outcomes in patients with AF treated with factor Xa inhibitor treatment.

Safety and Efficacy of Outpatient Parenteral Antibiotic Therapy (OPAT) in Patients With Infective Endocarditis: A Systematic Review and Meta‐Analysis

ABSTRACT Background Infective endocarditis (IE) is a life‐threatening infection requiring prolonged intravenous antimicrobial therapy. Outpatient parenteral antibiotic therapy (OPAT) has emerged as an alternative to prolonged hospitalization, but its safety and efficacy in IE remain debated. Hypothesis This systematic review and meta‐analysis aimed to evaluate the outcomes of OPAT in IE patients. Methods We systematically searched MEDLINE, Cochrane CENTRAL, Google Scholar, and Scopus for studies assessing OPAT in IE. Eligible studies included randomized controlled trials and observational studies reporting at least one relevant outcome (mortality, relapse, readmission, valve surgery, and adverse events). Pooled estimates were calculated using a random‐effects model, and heterogeneity was assessed using the I² statistic. Risk of bias was evaluated using the ROBINS‐I tool. Results A total of 25 studies involving 2654 patients were included in the analysis. Patients treated with OPAT had a mortality rate of 0% during the treatment period and 5% during follow‐up. The readmission rate was 16% during the treatment period, 4% of the patients had relapse, while 16% of patients underwent cardiac surgery. During follow‐up, the readmission rate was 19%, with a relapse rate of 2%, and 14% of patients underwent cardiac surgery. Sensitivity analyses did not significantly affect the results, highlighting the robustness of the findings. Conclusion OPAT appears to be safe and effective for IE patients, with low mortality and relapse rates. However, increased readmission rates and IV‐line complications warrant careful patient selection and monitoring. Further prospective trials are needed to refine OPAT protocols.

Questioning the Rhythm: A Closer Look at Heart Rate Trends in Atrial Fibrillation

Immune Checkpoint Inhibitor‐Related Myocarditis: A Single Center Observational Registry

ABSTRACT Introduction Immune checkpoint inhibitors (ICIs) are associated with myocarditis, which is rare but has a high mortality. This study aimed to describe cases of ICI‐related myocarditis at the University of Iowa Hospitals & Clinics and, in doing so, provide valuable insights into patient characteristics, treatment, and outcomes. Methods This single‐center observational registry included cases of ICI‐related myocarditis identified from 2009 to 2024. Data were collected retrospectively from electronic medical records and included demographics, cardiovascular risk factors, medications, and cancer characteristics. Between‐group comparisons for continuous data were conducted using unpaired Student's t ‐tests or the Wilcoxon rank‐sum test. Categorical data were analyzed with Fisher's exact test. Results Eighteen patients were included. The mean age was 74 ± 9.4 years with 61% being male. Compared to controls, patients with ICI‐related myocarditis had a significantly higher prevalence of coronary artery disease (36.8% vs. 7.5%, p  = 0.01) and obstructive sleep apnea (33% vs. 10%, p  = 0.03). They were less likely to have a normal sinus rhythm on baseline electrocardiogram (50% vs. 70%, p  < 0.01) and more likely to suffer from a major adverse cardiac event (MACE) (38.9% vs. 2.5%, p  < 0.01). Twelve (66.7%) of patients with ICI‐related myocarditis also had myasthenia gravis‐like overlap syndrome and 9 (50%) had myositis/rhabdomyolysis. Conclusions ICI‐related myocarditis at a tertiary care center is rare with a calculated incidence of 0.48%. Despite this, the disease has a high incidence of MACE. Patients with pre‐existing cardiovascular disease are at higher risk of developing ICI‐related myocarditis. Careful cardiovascular monitoring in patients undergoing ICI therapy is warranted.

Impact of Adherence to Guideline‐Directed Prevention Strategies on Clinical Outcomes in Patients With Coronary Artery Disease and Diabetes Mellitus Following Acute Coronary Syndrome: A 3‐Year Cohort Study

ABSTRACT Background Coronary artery disease (CAD) and diabetes mellitus (DM) significantly increase the risk after acute coronary syndrome. This study evaluated adherence to guideline‐directed secondary prevention strategies and demonstrated their substantial impact on reducing rehospitalization and mortality in this population. Methods A retrospective cohort study was conducted on 987 CAD and DM patients admitted for ACS between 2015 and 2018. Adherence to seven evidence‐based secondary prevention strategies was assessed: smoking cessation, physical activity, antiplatelet therapy, statins, blood pressure control, ACEi/ARB therapy, and SGLT‐2i therapy. Patients were categorized into groups based on the number of recommendations followed (0–2, 3–4, and 5+). Primary outcomes included rehospitalization and all‐cause mortality over a 3‐year follow‐up period. Results At baseline, only 12.4% of patients adhered to five or more recommendations, which dramatically increased to 71.9% by the 3‐year follow‐up. Individual adherence to each of blood pressure control (HR = 0.81, 95% CI: 0.70–0.94), ACEi/ARB therapy (HR = 0.77, 95% CI: 0.67–0.89), and SGLT‐2i therapy (HR = 0.79, 95% CI: 0.68–0.92) significantly reduced rehospitalization risk. Similarly, adherence to these therapies individually reduced mortality risk (HR = 0.78, 95% CI: 0.67–0.91; HR = 0.74, 95% CI: 0.63–0.87; and HR = 0.72, 95% CI: 0.61–0.85, respectively). Importantly, a stepwise increase in adherence was associated with a dose‐dependent reduction in mortality (HR = 0.65, 95% CI: 0.52–0.81, p  < 0.05). Conclusion This study highlights the critical role of comprehensive, multifactorial secondary prevention in its association with improved long‐term outcomes in patients with CAD and DM following ACS.

Trends in Atrial Fibrillation‐Related Mortality Among Older Adults With Obstructive Sleep Apnea in the United States, 1999–2020

ABSTRACT Background Atrial fibrillation (AF) and obstructive sleep apnea (OSA) frequently coexist and synergistically increase cardiovascular risk. While their pathophysiologic interplay is well established, national data on mortality trends involving both conditions are scarce. Methods We analyzed mortality data from the CDC WONDER platform (1999–2020), including adults aged ≥ 25 years with AF (ICD‐10 I48.x) listed as the underlying cause of death and OSA (G47.33) as a contributing condition. Age‐adjusted mortality rates (AAMRs) and average annual percent changes (AAPCs) were calculated using Joinpoint regression, stratified by sex, race/ethnicity, urbanization, region, and age. Results A total of 32,142 AF‐related deaths with OSA were identified. The overall AAMR was 0.60 per 100 000, increasing significantly over time (AAPC: 16.69%, 95% CI: 15.62–17.77). Mortality rose across all demographic groups, with the steepest increases among adults ≥ 85 years (AAPC: 19.40%), females (AAPC: 17.77%), rural residents (AAPC: 17.51%), and White individuals (AAPC: 16.95%). Regionally, the Midwest (AAMR: 0.79) and West (0.72) had the highest rates. State‐level variation ranged from 1.90 (Oregon) to 0.19 (Mississippi). Despite lower absolute AAMRs among Hispanic and Asian populations, significant upward trends were observed. OSA appears frequently underdiagnosed or untreated in high‐risk groups, potentially exacerbating AF mortality. Conclusions AF‐related mortality involving OSA has risen sharply over the past two decades, outpacing many other cardiovascular trends. These findings underscore the urgent need for integrated AF‐OSA screening and treatment pathways, with attention to underserved and disproportionately affected populations.

The Effect of Age on 1‐Year Readmissions in Atrial Fibrillation Patients: Trends and Insights From a Conflict‐Stricken Country

ABSTRACT Background Atrial fibrillation (AF) is a leading cause of cardiovascular morbidity and hospitalization worldwide. However, limited data exist on AF readmissions in low‐resource and conflict‐affected settings. This study investigates the impact of age on 1‐year readmission rates among AF patients in a Syrian tertiary hospital. Methods This retrospective observational cohort study was conducted at a tertiary Syrian center between June/2021–November/2023. Patients admitted with primary AF were included, while those with secondary AF or missing demographic data were excluded. Patients were stratified into three age groups: 18–50 years (Group 1), 51–70 years (Group 2), and > 70 years (Group 3). The primary outcome was all‐cause and cardiovascular‐related 1‐year readmissions, with secondary outcomes including readmission frequencies. Results A total of 657 AF patients were included, with a median age of 60 320 (52%) were males. One‐year readmission occurred in 64% of patients, with AF being the most common cause (75%). Group 1 had the highest smoking rates (70%). Group 3 had the highest rates of ischemic heart disease (47%), congestive cardiac failure (CCF) (35%), chronic kidney disease (15%, p  < 0.001) and chronic liver disease (20). Older age was significantly associated with increased readmissions (87% in Group 3 vs. 62% in Group 2 and 49% in Group 1, p  < 0.001). Frequent readmissions were more prevalent in Group 3 (≥ 3 admissions: 46%). Conclusion Older AF patients in a conflict‐affected setting experience significantly higher readmission rates. Addressing healthcare resource limitations and optimizing AF management strategies are crucial to improving outcomes in resource‐limited settings.