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Background: This Mendelian randomization (MR) study aimed to explore the causal relationship between the genetic predisposition to type 2 diabetes mellitus (T2DM) and aortic dissection (AD), and to assess associations with genetically predicted glycemic traits. The study sought to verify the inverse relationship between T2DM and AD using a more robust and unbiased method, building on the observational studies previously established. Materials and methods: The study employed a two-sample and multivariable MR approach to analyze genetic data from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) with 74,124 cases and 824,006 controls, and the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) involving up to 196,991 individuals. For AD data, FinnGen Release 10 was used, including 967 cases and 381,977 controls. The research focused on three foundational MR assumptions and controlled for confounders like hypertension. Genetic instruments were selected for their genome-wide significance, and multiple MR methods and sensitivity analyses were conducted. Results: The study revealed no significant effect of genetic predisposition to T2DM on the risk of AD. Even after adjusting for potential confounders, the results were consistent, indicating no causal relationship. Additionally, glycemic traits such as fasting glucose, fasting insulin, and HbA1c levels did not show a significant impact on AD susceptibility. The findings remained stable across various MR models and sensitivity analyses. In contrast, genetic liability to T2DM and glycemic traits showed a significant association with coronary artery disease (CAD), aligning with the established understanding. Conclusion: Contrary to previous observational studies, this study concludes that genetic predisposition to T2DM does not confer protection against AD. These findings underscore the imperative for further research, particularly in exploring the preventative potential of T2DM treatments against AD and to facilitate the development of novel therapeutic interventions.
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The catalytic relevance of Fe(IV) species in non-heme iron catalysis has motivated synthetic advances in well-defined five- and six-coordinate Fe(IV) complexes for a better understanding of their fundamental electronic structures and reactivities. Herein, we report the syntheses of FeDipp2 and FeMes2, a pair of unusual four-coordinate non-heme formally Fe(IV) complexes with S=1 ground states supported by strongly donating bisamide ligands. By combining spectroscopic characterization and computational modeling, we found that small variations in ligand aryl substituents resulted in substantial changes in both structures and bonding. This work highlights the strong donor capabilities and modularity of the bisamide ligand set. More broadly, it is a critical contribution to the utilization of ligand design to modulate molecular geometries and electronic structures of low-coordinate, high-valent iron complexes.
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BACKGROUND: The accuracy of electrocardiogram (ECG) interpretation by doctors are affected by the available clinical information. However, having a complete set of clinical details before making a diagnosis is very difficult in the clinical setting especially in the early stages of the admission process. Therefore, we developed an artificial intelligence-assisted ECG diagnostic system (AI-ECG) using natural language processing to provide screened key clinical information during ECG interpretation. METHODS: Doctors with varying levels of training were asked to make diagnoses from 50 ECGs using a common ECG diagnosis system that does not contain clinical information. After a two-week-blanking period, the same set of ECGs was reinterpreted by the same doctors with AI-ECG containing clinical information. Two cardiologists independently provided diagnostic criteria for 50 ECGs, and discrepancies were resolved by consensus or, if necessary, by a third cardiologist. The accuracy of ECG interpretation was assessed, with each response scored as correct/partially correct = 1 or incorrect = 0. RESULTS: The mean accuracy of ECG interpretation was 30.2% and 36.2% with the common ECG system and AI-ECG system, respectively. Compared to the unaided ECG system, the accuracy of interpretation was significantly improved with the AI-ECG system (P for paired t-test = 0.002). For senior doctors, no improvement was found in ECG interpretation accuracy, while an AI-ECG system was associated with 27% higher mean scores (24.3 ± 9.4% vs. 30.9 ± 10.6%, P = 0.005) for junior doctors. CONCLUSION: Intelligently screened key clinical information could improve the accuracy of ECG interpretation by doctors, especially for junior doctors.
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Inteligência Artificial , Cardiologistas , Humanos , Estudos Transversais , Competência Clínica , EletrocardiografiaRESUMO
Aminoboration of simple alkenes with nitrogen nucleophiles remains an unsolved problem in synthetic chemistry; this transformation can be catalyzed by palladium via aminopalladation followed by transmetalation with a diboron reagent. However, this catalytic process faces inherent challenges with instability of the alkylpalladium(II) intermediate toward ß-hydride elimination. Herein, we report a palladium/iron cocatalyzed aminoboration, which enables this transformation. We demonstrate these conditions on a variety of alkenes and norbornenes with an array of common nitrogen nucleophiles. In the developed strategy, the iron cocatalyst is crucial to achieving the desired reactivity by serving as a halophilic Lewis acid to release the transmetalation-active cationic alkylpalladium intermediate. Furthermore, it serves as a redox shuttle in the regeneration of the Pd(II) catalyst by reactivation of nanoparticulate palladium.
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BACKGROUND: Fluid resuscitation is necessary to correct the sepsis-induced hypoperfusion, which is contradictory to the treatment of heart failure. This study explored the association between fluid balance (FB) of the first 24 h after ICU admission and mortality in critically ill patients with heart failure and sepsis. METHODS: Data were extracted from the Medical Information Mart for Intensive Care database. The locally weighted scatterplot smoothing (Lowess) method was used to demonstrate the relationship between FB and in-hospital mortality. Groups were divided into high FB (≥ 55.85 ml/kg) and low FB (< 55.85 ml/kg) according to the cut-off value of FB using Receiver operating characteristic analysis and Youden index method. The primary outcome was in-hospital mortality. Subgroup analyses, multivariable logistic regression analyses, and Kaplan-Meier curves were used to detect the association and survival difference between groups. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) were performed to minimize the bias of confounding factors and facilitate the comparability between groups. RESULTS: A total of 936 patients were included. The Lowess curve showed an approximate positive linear relationship for FB and in-hospital mortality. In the multivariable logistic regression adjusted model, high FB showed strong associations with in-hospital mortality (OR 2.53, 95% CI 1.60-3.99, p < 0.001) as compared to the low FB group. In IPTW and PSM models, high FB consistently showed higher in-hospital mortality (IPTW model: OR 1.94, 95% CI 1.52-2.49, p < 0.001; PSM model: OR 2.93, 95% CI 1.75-4.90, p < 0.001) and 30-day mortality (IPTW model: OR 1.65, 95% CI 1.29-2.10, p < 0.001; PSM model: OR 2.50, 95% CI 1.51-4.15, p < 0.001), compared with the low FB group. CONCLUSION: For critically ill patients with heart failure and sepsis, high FB within the first 24 h after ICU admission could serve as an independent risk factor for in-hospital mortality and 30-day mortality. The avoidance of fluid overload exerts important effects on reducing mortality in such patients.
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Insuficiência Cardíaca , Sepse , Humanos , Estado Terminal/terapia , Unidades de Terapia Intensiva , Pontuação de Propensão , Equilíbrio Hidroeletrolítico , Mortalidade Hospitalar , Insuficiência Cardíaca/terapia , Estudos RetrospectivosRESUMO
Many studies have reported various minimally invasive techniques for continuous-flow left ventricular assist device implantation. There is no consensus on whether minimally invasive techniques can bring more benefits for patients compared with the conventional technique, due to the limited number of patients and diverse results in current studies. Our meta-analysis mainly discussed the comparison of minimally invasive and conventional techniques. We searched controlled trials from PubMed, Cochrane Library, and Embase databases until Dec 11, 2020. Perioperative and postoperative outcomes were analyzed among 10 included studies. The protocol has been registered with PROSPERO (CRD42020221532). There were no statistical differences in the 30-day mortality (OR 0.57; 95% CI 0.29 to 1.14), 6-month mortality (OR 0.66; 95% CI 0.41 to 1.05), neurological dysfunction (OR 1.10; 95% CI 0.69 to 1.76), major infection (OR 0.68; 95% CI 0.36 to 1.28), and pump thrombus (OR 1.49; 95% CI 0.63 to 3.52) among the cohorts. Minimally invasive techniques were associated with lower incidences of major bleeding (OR 0.39; 95% CI 0.22 to 0.68), severe right heart failure (OR 0.43; 95% CI 0.23 to 0.81), and less blood-product utilization (SMD -0.44). Sensitivity analysis suggested that minimally invasive techniques were associated with a lower incidence of respiratory failure (OR 0.50; 95% CI 0.26 to 0.96) and shorter mechanical ventilation time (SMD -0.53). Subgroup analysis demonstrated that patients, implanted with a centrifugal pump by minimally invasive techniques, were associated with a shorter length of intensive care unit (ICU) stay (SMD -0.27) and hospital stay (SMD -0.42), and less blood-product utilization (SMD -0.26). In conclusion, minimally invasive techniques can reduce the risks of major bleeding, severe right heart failure, and blood-product utilization, as well as have positive impacts on reducing mechanical ventilation time and the risk of respiratory failure. Minimally invasive centrifugal pump implantation can reduce the length of ICU and hospital stay.
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Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Respiratória , Insuficiência Cardíaca/cirurgia , Humanos , Tempo de Internação , Estudos RetrospectivosRESUMO
Dilithium amides have been developed as a bespoke and general ligand for iron-catalyzed Kumada-Tamao-Corriu cross-coupling reactions, their design taking inspiration from previous mechanistic and structural studies. They allow for the cross-coupling of alkyl Grignard reagents with sp2-hybridized electrophiles as well as aryl Grignard reagents with sp3-hybridized electrophiles. This represents a rare example of a single iron-catalyzed system effective across diverse coupling reactions without significant modification of the catalytic protocol, as well as remaining operationally simple.
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Amidas/química , Ânions/química , Ferro/química , Catálise , Indicadores e Reagentes , Ligantes , Estrutura MolecularRESUMO
BACKGROUND: Due to the lack of donor hearts, many studies have assessed the prognosis of heart failure (HF) patients treated with a continuous-flow left ventricular assist device (CF-LVAD). However, previous results have not been consistent and minimal data is available regarding long-term outcomes. There is no consensus on whether CF-LVAD as a bridge or destination therapy (DT) can equal orthotopic heart transplantation (HTx). The purpose of our study is to compare clinical outcomes between CF-LVAD and HTx in adults. METHODS: We searched controlled trials from PubMed, Cochrane Library, and Embase databases until July 1, 2020. The mortality at different time points and adverse events were analyzed among 12 included studies. RESULTS: No significant differences were found in mortality at one-year [odds ratio (OR) =1.08; 95% CI: 0.97-1.21], two-year (OR =1.01; 95% CI: 0.91-1.12), three-year (OR =1.02; 95% CI: 0.69-1.51), and five-year (OR =1.02; 95% CI: 0.93-1.11), as well as the comparison of stroke, bleeding, and infection between CF-LVAD as a bridge versus HTx. The pooled analysis of one-year mortality (OR =2.76; 95% CI: 0.38-20.18) and two-year mortality (OR =1.64; 95% CI: 0.22-12.23) revealed no significant difference between CF-LVAD DT and HTx. Comparisons of adverse events showed no differences in bleeding or infection, but a higher risk of stroke (OR =5.09; 95% CI: 1.74-14.84) for patients treated with CF-LVAD DT than with HTx. CONCLUSIONS: CF-LVAD as a bridge results in similar outcomes as HTx within five years. CF-LVAD as a DT is associated with similar one-year and two-year mortality, but carries a higher risk of stroke, as compared with HTx.
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The development of an air-stable iron(III)-based precatalyst for the Suzuki-Miyaura cross-coupling reaction of alkyl halides and unactivated aryl boronic esters is reported. Despite benefits to cost and toxicity, the proclivity of iron(II)-based complexes to undergo deactivation via oxidation or hydrolysis is a limiting factor for their widespread use in cross-coupling reactions compared to palladium-based or nickel-based complexes. The new octahedral iron(III) complex demonstrates long-term stability on the benchtop as assessed by a combination of 1H NMR spectroscopy, Mössbauer spectroscopy, and its sustained catalytic activity after exposure to air. The improved stability of the iron-based catalyst facilitates an improved protocol in which Suzuki-Miyaura cross-coupling reactions of valuable substrates can be assembled without the use of a glovebox and access a diverse scope of products similar to reactions assembled in the glovebox with iron(II)-based catalysts.
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Fast, base-promoted protodeboronation of polyfluoroaryl and heteroaryl boronic acids complicates their use in Suzuki-Miyaura coupling (SMC) because a base is generally required for catalysis. We report a "cationic" SMC method using a PAd3-Pd catalyst that proceeds at rt in the absence of a base or metal mediator. A wide range of sensitive boronic acids, particularly polyfluoroaryl substrates that are poorly compatible with classic SMC conditions, undergo clean coupling. Stoichiometric experiments implicate the intermediacy of organopalladium cations, which supports a long-postulated cationic pathway for transmetalation in SMC.