6G Network AI Architecture for Everyone-Centric Customized Services

Mobile communication standards were developed for enhancing transmission and network performance by using more radio resources and improving spectrum and energy efficiency. How to effectively address diverse user requirements and guarantee everyone's Quality of Experience (QoE) remains an open problem. The Sixth Generation (6G) mobile systems will solve this problem by utilizing heterogenous network resources and pervasive intelligence to support everyone-centric customized services anywhere and anytime. In this article, we first coin the concept of Service Requirement Zone (SRZ) on the user side to characterize and visualize the integrated service requirements and preferences of specific tasks of individual users. On the system side, we further introduce the concept of User Satisfaction Ratio (USR) to evaluate the system's overall service ability of satisfying a variety of tasks with different SRZs. Then, we propose a network Artificial Intelligence (AI) architecture with integrated network resources and pervasive AI capabilities for supporting customized services with guaranteed QoEs. Finally, extensive simulations show that the proposed network AI architecture can consistently offer a higher USR performance than the cloud AI and edge AI architectures with respect to different task scheduling algorithms, random service requirements, and dynamic network conditions

Dosing and safety profile of aficamten in symptomatic obstructive hypertrophic cardiomyopathy: results from from SEQUOIA‐HCM

Background: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA‐HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). Methods and Results: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5–20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site‐interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8–24), and washout (weeks 24–28), and included major adverse cardiac events, new‐onset atrial fibrillation, implantable cardioverter‐defibrillator discharges, LVEF <50%, and treatment‐emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5‐, 10‐, 15‐, and 20‐mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by −0.9% (95% CI, −1.3 to −0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per‐protocol dose reduction for site‐interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment‐emergent adverse events were similar between treatment groups, including atrial fibrillation. Conclusions: A site‐based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA‐HCM

Alterations of Fecal Metabolome Associated with BBIBP-CorV Vaccines against the SARS-CoV-2 Virus

Background: The SARS-CoV-2 vaccine has been implemented in response to the 2019 Coronavirus Disease (COVID-19) pandemic worldwide. Dysregulation of gut metabolite is associated with COVID-19 patients. However, the effect of vaccination on the gut metabolite remains unknown, and it is critical to investigate the shifts in metabolic profiles following vaccine treatment. Methods: In the present study, we conducted a case-control study to assess the fecal metabolic profiles between individuals who received two doses of intramuscular injection of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) (n = 20), and matched unvaccinated controls (n = 20) using untargeted gas chromatography and time-of-flight mass spectrometry (GC-TOF/MS). Results: Significant different metabolic profiles were observed between subjects receiving SARS-CoV-2 virus vaccines and the unvaccinated. Among a total of 243 metabolites from 27 ontology classes identified in the study cohort, 64 metabolic markers and 15 ontology classes were dramatically distinct between vaccinated and unvaccinated individuals. There were 52 enhanced (such as Desaminotyrosine, Phenylalanine) and 12 deficient metabolites (such as Octadecanol, 1-Hexadecanol) in vaccinated individuals. Along with altered metabolic compositions, multiple functional pathways in Small MoleculePathway Database (SMPDB) and Kyoto Encyclopedia of Genes and Genomes (KEGG) varied between groups. Our results indicated that urea cycle; alanine, aspartate, and glutamate metabolism; arginine and proline metabolism; phenylalanine metabolism and tryptophan metabolism were abundant after vaccination. Additionally, correlation analysis showed that intestinal microbiome was related to alteration in metabolite composition and functions. Conclusions: The present study indicated the alterations in the gut metabolome after COVID-19 vaccination and the findings provide a valuable resource for in-depth exploration of mechanisms between gut metabolite and SARS-CoV-2 virus vaccines

Discordance of Circulating Non-HDL Cholesterol with LDL Cholesterol Concerning Long-Term Prognosis in Statin-Treated Individuals with Acute Coronary Syndrome and Previous Coronary Artery Bypass Grafting Undergoing Percutaneous Coronary Intervention

Background: Some individuals who maintain desirable low-density lipoprotein cholesterol (LDL-C) levels still experience the progression of atherosclerosis, which may eventually lead to cardiovascular events. Non-high-density lipoprotein cholesterol (non-HDL-C) levels are quantified to assess residual risk in statin-treated patients with coronary heart disease. The study aimed to estimate the predictive performance of discordance between non-HDL-C and LDL-C on clinical prognosis in statin-treated patients with previous coronary artery bypass grafting (CABG). Methods: 468 statin-treated patients with previous CABG undergoing percutaneous coronary intervention (PCI) as a secondary coronary treatment due to acute coronary syndrome (ACS) were retrospectively enrolled in this study. The definition of major adverse cardiovascular events (MACEs) was a composite endpoint of cardiovascular death, recurring myocardial infarction, and a need for repeat revascularization. Cox proportional hazards modeling, restricted cubic splines regression, and discordance analysis were conducted to the association between all lipid parameters and the occurrence of MACEs. Discordant values were defined as LDL-C concentrations ≤1.8 mmol/L accompanied by non-HDL-C >2.6 mmol/L. Results: MACEs occurred in 95 patients over a median follow-up period of 744.5 days. Cox models demonstrated that increased concentrations of non-HDL-C and LDL-C levels were independent risk indicators of MACEs (p < 0.001). The restricted cubic spline analysis revealed a linear relationship between non-HDL-C concentrations and MACEs (p-nonlinear: 0.26), whereas a nonlinear relationship was observed between LDL-C concentrations and MACEs (p < 0.01). In the subgroup analysis, the spline curves revealed that the odds of the individuals with desirable LDL-C levels suffering MACEs emerged when non-HDL-C levels were above 2.07 mmol/L. Individuals who exhibited discordance involving high non-HDL-C/low LDL-C levels had an elevated risk of experiencing MACEs compared to those with concordantly low LDL-C and low non-HDL-C levels [hazard ratios (HRs) = 2.44, 95% confidence interval (CI) = 1.14–5.22, p = 0.02]. Conclusions: Non-HDL-C levels could predict the residual risk of MACEs in ACS patients with previous CABG and statin therapy that underwent percutaneous coronary intervention. A discordance between non-HDL-C and LDL-C in individuals with desirable LDL-C levels could be useful in identifying those with a residual risk of cardiovascular complications

Relation of perceptions of educational environment with mindfulness among Chinese medical students: a longitudinal study

Background: Perceived educational environment influences academic outcomes, such as academic achievement, students’ behaviors, well-being, socio-emotional adjustment and explicit self-esteem. Mindfulness is a set of skills that are beneficial to physical and mental health. Recently, it has been increasingly discussed about its usefulness in education, but little research has explored whether mindfulness can predict perceptions of educational environment. The aim of this study was to explore Chinese medical students’ perceptions of learning environment and their relationship with mindfulness. Methods: Medical students at the Second Xiangya Hospital of Central South University (N=431) completed the Chinese version of Dundee Ready Educational Environment Measure (DREEM-C) and the Kentucky Inventory of Mindfulness Skills (KIMS-C). One year later, a subgroup of the cohort (N=231) completed the DREEM-C again. Independent-samples t-test, variance analysis, correlation analysis, and hierarchical multiple regression (HMR) were conducted. Results: DREEM-C total and subscales scores were net positive, but with room for improvement. Perceptions differed in relation to gender, academic year, and age. KIMS-C scores correlated with DREEM-C scores. The predictive effect persisted 1 year later. Conclusions: Medical students had net-positive perceptions about their learning environment. Higher mindfulness scores were associated with greater satisfaction with the environment and this association showed persistence

Relation of perceptions of educational environment with mindfulness among Chinese medical students: a longitudinal study

Background: Perceived educational environment influences academic outcomes, such as academic achievement, students’ behaviors, well-being, socio-emotional adjustment and explicit self-esteem. Mindfulness is a set of skills that are beneficial to physical and mental health. Recently, it has been increasingly discussed about its usefulness in education, but little research has explored whether mindfulness can predict perceptions of educational environment. The aim of this study was to explore Chinese medical students’ perceptions of learning environment and their relationship with mindfulness. Methods: Medical students at the Second Xiangya Hospital of Central South University (N=431) completed the Chinese version of Dundee Ready Educational Environment Measure (DREEM-C) and the Kentucky Inventory of Mindfulness Skills (KIMS-C). One year later, a subgroup of the cohort (N=231) completed the DREEM-C again. Independent-samples t-test, variance analysis, correlation analysis, and hierarchical multiple regression (HMR) were conducted. Results: DREEM-C total and subscales scores were net positive, but with room for improvement. Perceptions differed in relation to gender, academic year, and age. KIMS-C scores correlated with DREEM-C scores. The predictive effect persisted 1 year later. Conclusions: Medical students had net-positive perceptions about their learning environment. Higher mindfulness scores were associated with greater satisfaction with the environment and this association showed persistence

The correlation between peripartum cardiomyopathy and autoantibodies against cardiovascular receptors.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is characterized by left ventricular systolic dysfunction and heart failure. However, its pathogenesis is not clear. Our preliminary study revealed that autoantibodies against β1-adrenergic receptors (β1R-AABs) and M2-muscarinic receptors (M2R-AABs) participated in heart failure regardless of primary heart disease. Whether β1R-AABs and M2R-AABs participate in the pathogenesis of PPCM is still unknown. METHODS: Totally 37 diagnosed PPCM patients and 36 normal pregnant women were enrolled in this study. Clinical assessment and 2-dimensional echocardiographic studies as well as the measurement of β1R-AABs or M2R-AABs by enzyme linked immunosorbent assay (ELISA) were performed. RESULTS: The positive rates for β1R-AABs and M2R-AABs were 59.5% (22/37) and 45.9% (17/37) in PPCM patients, and 19.4% (7/36) (P<0.001) and 16.67% (6/36) (P<0.001) in normal pregnant women, respectively. Both β1R-AABs and M2R-AABs had a positive correlation with serum expression level of NT-proBNP, left ventricular dimension and NYHA FC (rs: 0.496-0.892, P<0.01). In addition, a negative correlation between the activity of β1R-AABs and M2R-AABs and LVEF, LVFS was observed (rs: -0.488-0.568, P<0.01). Moreover, autoantibodies against cardiovascular receptors increased the risk of the onset of PPCM (OR = 18.786, 95% confidence interval 1.926-183.262, P = 0.012). CONCLUSIONS: The β1R-AABs and M2R-AABs reveal a significant elevation and are correlated with the increased left ventricular dimension and worse cardiac contraction function. The autoantibodies of cardiovascular receptors are independent risk factors for the onset of PPCM

Retinol exerts therapeutic effect on myocardial infarction through regulation of immune inflammatory cells and Cx43 expression

Purpose: To investigate the effect of retinol on cardiac fibroblast proliferation in vitro and on fibrosis formation in mice in vivo. Methods: Proliferative potential of fibroblasts was determined using cell counting kit-8 assay. Acute myocardial infarction (AMI) was induced in mice via ligation of the left side coronary artery. In myocardial tissues, concentration of TNF-α was determined using enzyme-linked immunosorbent assay (ELISA) assay. Results: Exposure to retinol significantly suppressed cardiac fibroblast proliferation under ischemia, when compared to untreated fibroblasts (p &lt; 0.05). However, exposure of cardiac fibroblasts to retinol did not produce toxicity at a dose of 10 μM under normal conditions. In contrast, exposure to normal levels of oxygen, glutamine and glucose significantly reversed the inhibitory potential of retinol against fibroblasts during ischemia (p &lt; 0.05). Treatment of mice with retinol at a dose of 5 mg/kg reversed the AMI-mediated increase in hydroxyproline level in myocardial tissues. Retinol treatment of AMI mice caused significant elevation in the number of CD31+ capillaries in myocardial tissues. Increase in TNF-α by AMI in cardiac tissues of mice was reversed by treatment with retinol at a dose of 5 mg/kg. The retinol treatment also caused significant reversal of AMI-induced down-regulation of Cx43 protein (p &lt; 0.05). Conclusion: Retinol enhanced the proliferation of fibroblasts under ischemic conditions and prevented fibrosis in mice with AMI. Moreover, retinol targeted TNF-α production and upregulated Cx43 expression in myocardial tissues of mice with AMI. Thus, retinol may be useful for the management of myocardial infarction

Cigarette smoking status alters dysbiotic gut microbes in hypertensive patients

Abstract Smoking not only is one of the most important risk factors of hypertension (HTN), but also alters the composition of gut microbiota (GM) in previous studies. Although dysbiosis of GM has been implicated in HTN, how GM alters in patients with HTN under smoking status is still not clear. This study aimed to explore the difference in intestinal microflora among smokers with HTN (S‐HTN), nonsmokers with HTN (NS‐HTN), and smokers without HTN (S‐CTR) and identify whether cigarette smoking led to disordered intestinal microbiota in patients with HTN. Metagenomic sequencing analysis of fecal specimens was conducted in nonsmokers without HTN (NS‐CTR, n = 9), S‐CTR (n = 9), NS‐HTN (n = 18), and S‐HTN (n = 23). Compared with S‐CTR or NS‐HTN, the GM in S‐HTN was disordered, with lower microbial α‐diversity and significant difference of β‐diversity on axes as compared to S‐CTR at genus and species level. The microbial enterotype in S‐HTN was inclined to Prevotella‐dominant type. Dramatic changes in the intestinal genera and species composition were observed in S‐HTN, including reduced enrichment of Phycisphaera and Clostridium asparagiforme. Moreover, the intestinal function altered in S‐HTN. Therefore, the findings of the present study revealed GM disorders in S‐HTN and clarified the role of smoking in impairing the intestinal microbiome in HTN. Tobacco control is particularly important for improving GM in patients with HTN, and might be beneficial in preventing future cardiovascular events