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Patient baseline characteristics, especially patients age, gender, and body mass index did not influence EDEL incidence. Additional posterior box isolation did not increase the incidence of EDEL. In patients diagnosed with EDEL, mean catheter contact force during posterior wall ablation was higher (11.9 ± 1.8 vs. 14.7 ± 3 g, p < .001), mean RF duration was shorter (11.9 ± 1 vs. 10.7 ± 1.2 s, p < .001), while achieved ablation indexwas not different between groups (434 ± 4.9 vs. 433 ± 9.5, n.s.).
Incidence of EDEL after CLOSE-guided-50 W-HPSD PVI is lower compared to historical cohorts using standard-power RF settings. Catheter contact force during posterior HPSD ablation should not exceed 15 g.
Incidence of EDEL after CLOSE-guided-50 W-HPSD PVI is lower compared to historical cohorts using standard-power RF settings. Catheter contact force during posterior HPSD ablation should not exceed 15 g.Dynamics with an orientational degree of freedom are fundamental in biological events. Probes with polarized luminescence enable a determination of the orientation. Lanthanide-doped nanocrystals can provide more precise analysis than quantum dots due to the nonphotoblinking/bleaching nature and the multiple line-shaped emission. However, the intrinsic polarization property of the original nanocrystals often deteriorates in complex physiological environments because the colloidal stability easily breaks and the probes aggregate in the media with abundant salts and macromolecules. Engineering the surface chemistry of the probes is thus essential to be compatible with biosystems, which has remained a challenging task that should be exclusively addressed for each specific probe. Here, we demonstrate a facile and efficient surface functionalization of lanthanide-doped nanorods by zwitterionic block copolymers. Due to the steric interaction and the intrinsic zwitterionic nature of the polymers, high colloidal stability of the zwitterionic nanorod suspension is achieved over wide ranges of pH and concentration of salts, even giving rise to the lyotropic liquid crystalline behavior of the nanorods in physiological media. The shear-aligned ability is shown to be unaltered by the coated polymers, and thus, the strongly polarized emission of Eu3+ is preserved. Besides, biological experiments reveal good biocompatibility of the zwitterionic nanorods with negligible nonspecific binding. This study is a stepping stone for the use of the nanorods as orientation probes in biofluids and validates the strategy of coupling zwitterions to lanthanide-doped nanocrystals for various bioapplications.
The validity of functional assessment of coronary artery disease with fractional flow reserve (FFR) and/or instantaneous wave-free ratio (iFR) in patients with severe aortic stenosis (AS) might be affected by AS per se and other factors, including diabetes mellitus.
We aimed to evaluate the impact of diabetic status on FFR performance in severe AS.
The functional significance of 416 stenoses of intermediate angiographic severity in 221 patients with severe AS was assessed with iFR and FFR. Patients treated with insulin or oral hypoglycemic agents were classified as diabetic patients.
Of 221 enrolled patients, 68 (32.1%) patients were diabetic. A total of 128 (30.8%) lesions in patients with and 288 in patients without diabetes mellitus were assessed. The mean (SD) FFR was 0.85 (0.07), and iFR was 0.90 (0.04) with no difference between nondiabetic and diabetic patients. Good agreement between iFR and FFR was confirmed for non-diabetic (ICC, 0.83 [95% confidence interval, CI, 0.79-0.86]) and diabetic (ICC, 0.82 [95% CI, 0.76-0.87]) patients. Among patients without diabetes mellitus, the optimal cutoff value for FFR to detect iFR ≤0.89 was 0.81 with sensitivity and specificity of 96.6% and 100.0%. The optimal cutoff value for FFR to detect iFR ≤0.89 for diabetic patients was 0.83 with sensitivity and specificity of 98.0% and 100.0%.
In patients with severe AS, FFR correlates well with iFR. However, the optimal threshold for FFR to identify significant ischemia (iFR ≤0.89) in those patients may differ from the standard threshold of FFR ≤0.80 and might be affected by the diabetic status.
In patients with severe AS, FFR correlates well with iFR. However, the optimal threshold for FFR to identify significant ischemia (iFR ≤0.89) in those patients may differ from the standard threshold of FFR ≤0.80 and might be affected by the diabetic status.Individual success and failure in social cooperation matter not only to oneself but also to teammates. However, the common and distinct neural activities underlying salient success and failure in social cooperation are unclear. In this functional magnetic resonance imaging (fMRI) study, participants in the social group (Experiment one) cooperated with two human beings during a dice-gambling task, whereas those in the nonsocial group (Experiment two) cooperated with two computers. The social group reported more pride in success and more guilt in failure. The fMRI results in Experiment one demonstrated that left temporoparietal junction (LTPJ) activation increased exclusively with linearly changing unexpected success, whereas increasing anterior cingulate cortex (ACC) activation was only coupled with increasing unexpectedness of failure. Moreover, the dorsal medial prefrontal cortex (dMPFC) and left anterior insula were recruited in both success and failure feedback conditions. Dynamic causality model analysis suggested that the dMPFC first received information from the LTPJ and ACC separately and then returned information to these regions. The between-experiment comparison showed more dMPFC activity in social versus nonsocial contexts irrespective of success and failure feedback. Our findings shed light on the common and distinct neural substrates involved in processing success and failure feedback in social cooperation.
Prior coronary artery bypass graft surgery (CABG) patients undergoing percutaneous coronary intervention (PCI) are often older and present with multiple comorbidities. Ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) has emerged as an effective bleeding-avoidance strategy among high-risk patients.
We aimed to examine the effects of ticagrelor with or without aspirin in prior CABG patients undergoing PCI within the TWILIGHT trial.
After 3 months of ticagrelor plus aspirin, patients were randomised to either aspirin or placebo, in addition to ticagrelor, for 12 months and compared by prior CABG status. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The key secondary endpoint was all-cause death, myocardial infarction (MI), or stroke.
Out of 7,119 patients, a total of 703 (10.8%) patients had prior CABG within the randomised cohort. Prior CABG patients had more comorbidities and a higher incidence of BARC type 2, 3, or 5 bleeding and death, MI or stroke at 1 year after randomisation, compared with patients without prior CABG. Ticagrelor monotherapy was associated with significantly less BARC 2, 3, or 5 bleeding among prior CABG patients compared with DAPT (4.9% vs 9.6%, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.28 to 0.90; p
=0.676) and similar rates of death, MI or stroke (10.0% vs 8.7%, HR 1.14, 95% CI 0.70 to 1.87; p
=0.484). When comparing target vessel type, treatment effects were consistent among graft- and native-vessel interventions.
In high-risk patients with prior CABG, ticagrelor monotherapy reduced bleeding without compromising ischaemic outcomes compared with ticagrelor plus aspirin.
In high-risk patients with prior CABG, ticagrelor monotherapy reduced bleeding without compromising ischaemic outcomes compared with ticagrelor plus aspirin.
Agonistic αCD40 therapy has been shown to inhibit cancer progression in only a fraction of patients. Understanding the cancer cell-intrinsic and microenvironmental determinants of αCD40 therapy response is therefore crucial to identify responsive patient populations and to design efficient combinatorial treatments. Here, we show that the therapeutic efficacy of αCD40 in subcutaneous melanoma relies on preexisting, type 1 classical dendritic cell (cDC1)-primed CD8+ T cells. However, after administration of αCD40, cDC1s were dispensable for antitumor efficacy. Instead, the abundance of activated cDCs, potentially derived from cDC2 cells, increased and further activated antitumor CD8+ T cells. Hence, distinct cDC subsets contributed to the induction of αCD40 responses. In contrast, lung carcinomas, characterized by a high abundance of macrophages, were resistant to αCD40 therapy. Combining αCD40 therapy with macrophage depletion led to tumor growth inhibition only in the presence of strong neoantigens. Accordingly, treatment with immunogenic cell death-inducing chemotherapy sensitized lung tumors to αCD40 therapy in subcutaneous and orthotopic settings. Genipin manufacturer These insights into the microenvironmental regulators of response to αCD40 suggest that different tumor types would benefit from different combinations of therapies to optimize the clinical application of CD40 agonists.
This work highlights the temporal roles of different dendritic cell subsets in promoting CD8+ T-cell-driven responses to CD40 agonist therapy in cancer.
This work highlights the temporal roles of different dendritic cell subsets in promoting CD8+ T-cell-driven responses to CD40 agonist therapy in cancer.Researchers have paid relatively little attention to the role that sexual and gender violence play in reinforcing neoliberal discourse. We address this issue by demonstrating that the portrayal of women and girls in the mainstream media, female body practices based on this portrayal, gendered sexual-agency norms, sexual harassment, and rape are not only sexualized and violent, but they also display a common set of cultural scripts drawn from both patriarchal and neoliberal discourse. We thus conclude that these images, practices, and norms are forms of sexualized violence that reinforce patriarchal and neoliberal discourse and, thus, the gender and class orders.Chemical or enzymatic biotinylation of proteins is widely used in various studies, and proximity-dependent biotinylation coupled to mass spectrometry is a powerful approach for analyzing protein-protein interactions in living cells. We recently developed a simple method to enrich biotinylated peptides using Tamavidin 2-REV, an engineered avidin-like protein with reversible biotin-binding capability. However, the level of biotinylated proteins in cells is low; therefore, large amounts of cellular proteins were required to detect biotinylated peptides. In addition, the enriched biotinylated peptide solution contained many contaminant ions. Here, we optimized the workflow for efficient enrichment of biotinylated peptides and removal of contaminant ions. The efficient recovery of biotinylated peptides with fewer contaminant ions was achieved by heat inactivation of trypsin, prewashing Tamavidin 2-REV beads, clean-up of biotin solution, mock elution, and using optimal temperature and salt concentration for elution.