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Abstract Aims This study aims to evaluate the prognostic value of mean corpuscular haemoglobin concentration (MCHC) on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results We analysed HFpEF participants from the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline data (n = 1747). Patients were grouped into hypochromia or non‐hypochromia group according to a MCHC cut‐off level of 330 g/L. Cox proportional hazard model was used to explore the prognostic value of hypochromia on the long‐term clinical outcomes (the primary endpoint [composite of cardiovascular mortality, HF hospitalization and aborted cardiac arrest], any‐cause and HF hospitalization, all‐cause and cardiovascular mortality). Patients were further stratified according to baseline estimated glomerular filtration rate (eGFR) to explore the impact of renal dysfunction on the prognostic value of hypochromia. Baseline hypochromia was prevalent (n = 662, 37.9%) and strongly associated with worse clinical outcomes. In patients with worse renal function (eGFR

Abstract Background The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for myocardial repair. Nevertheless, the ideal scaffold for BCP is unknown. Objective We investigated whether the decellularized placenta (DP) could serve as natural scaffold material to create a BCP for myocardial repair. Methods and results A BCP was created by seeding human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs; 1 × 106/cm2) onto DP. The functional and electrophysiological properties of the BCP were first characterized by in vitro analysis and optical mapping. Next, in vivo therapeutic efficacy of the BCP was evaluated in a rat model of myocardial infarction (MI), created by left descending coronary artery ligation (MI + BCP group), and compared with MI alone (MI group), transplantation of DP (MI + DP group), and hiPSC-CMs (MI + CM group). Cytokine profiling demonstrated that the BCP contained multiple growth and angiogenic factors, including vascular endothelial growth factor, platelet-derived growth factor, insulin-like growth factor-1, basic fibroblast growth factor, angiogenin, and angiopoietin-2. In vitro optical mapping showed that the BCP exhibited organized mechanical contraction and synchronized electrical propagation. RNA sequencing showed that DP enhanced the maturation of hiPSC-CMs compared with the monolayer of cultured hiPSC-CMs. At 4 weeks follow-up, the BCP significantly improved left ventricular (LV) function, as determined by LV ejection fraction, fractional shortening, + dP/dtmax, and end-systolic pressure-volume relationship, compared with the MI, MI + DP, and MI + CM groups. Moreover, histological examination revealed that engraftment of the BCP at the infarct zone decreased infarct size and increased cell retention and neovascularization compared with the MI, MI + DP, and MI + CM groups. Conclusions Our results demonstrate that a DP scaffold contains multiple growth and angiogenic factors that enhance the maturation and survival of seeded hiPSC-CMs. Transplantation of a BCP is superior to DP or hiPSC-CMs alone in reducing infarct size and improving cell retention and neovascularization, thus providing a novel therapy for myocardial repair following MI.

Background: It is known that oral diseases such as periodontal (gum) disease are closely linked to various systemic diseases and disorders. Deep learning advances have the potential to make major contributions to healthcare, particularly in the domains that rely on medical imaging. Incorporating non-imaging information based on clinical and laboratory data may allow clinicians to make more comprehensive and accurate decisions. Methods: Here, we developed a multimodal deep learning method to predict systemic diseases and disorders from oral health conditions. A dual-loss autoencoder was used in the first phase to extract periodontal disease-related features from 1188 panoramic radiographs. Then, in the second phase, we fused the image features with the demographic data and clinical information taken from electronic health records (EHR) to predict systemic diseases. We used receiver operation characteristics (ROC) and accuracy to evaluate our model. The model was further validated by an unseen test dataset. Findings: According to our findings, the top three most accurately predicted chapters, in order, are the Chapters III, VI and IX. The results indicated that the proposed model could predict systemic diseases belonging to Chapters III, VI and IX, with AUC values of 0.92 (95% CI, 0.90–94), 0.87 (95% CI, 0.84–89) and 0.78 (95% CI, 0.75–81), respectively. To assess the robustness of the models, we performed the evaluation on the unseen test dataset for these chapters and the results showed an accuracy of 0.88, 0.82 and 0.72 for Chapters III, VI and IX, respectively. Interpretation: The present study shows that the combination of panoramic radiograph and clinical oral features could be considered to train a fusion deep learning model for predicting systemic diseases and disorders.

Abstract Background Optimal cell type as cell-based therapies for heart failure (HF) remains unclear. We sought to compare the safety and efficacy of direct intramyocardial transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) in a porcine model of HF. Methods Eight weeks after induction of HF with myocardial infarction (MI) and rapid pacing, animals with impaired left ventricular ejection fraction (LVEF) were randomly assigned to receive direct intramyocardial injection of saline (MI group), 2 × 108 hESC-CMs (hESC-CM group), or 2 × 108 hiPSC-MSCs (hiPSC-MSC group). The hearts were harvested for immunohistochemical evaluation after serial echocardiography and hemodynamic evaluation and ventricular tachyarrhythmia (VT) induction by in vivo programmed electrical stimulation. Results At 8 weeks post-transplantation, LVEF, left ventricular maximal positive pressure derivative, and end systolic pressure-volume relationship were significantly higher in the hiPSC-MSC group but not in the hESC-CM group compared with the MI group. The incidence of early spontaneous ventricular tachyarrhythmia (VT) episodes was higher in the hESC-CM group but the incidence of inducible VT was similar among the different groups. Histological examination showed no tumor formation but hiPSC-MSCs exhibited a stronger survival capacity by activating regulatory T cells and reducing the inflammatory cells. In vitro study showed that hiPSC-MSCs were insensitive to pro-inflammatory interferon-gamma-induced human leukocyte antigen class II expression compared with hESC-CMs. Moreover, hiPSC-MSCs also significantly enhanced angiogenesis compared with other groups via increasing expression of distinct angiogenic factors. Conclusions Our results demonstrate that transplantation of hiPSC-MSCs is safe and does not increase proarrhythmia or tumor formation and superior to hESC-CMs for the improvement of cardiac function in HF. This is due to their immunomodulation that improves in vivo survival and enhanced angiogenesis via paracrine effects.

Summary: Renal denervation (RD) is a potential novel nonpharmacological therapy for heart failure (HF). We performed bilateral catheter-based RD in 10 adult pigs and compared them with 10 control subjects after induction of HF to investigate the long-term beneficial effects of RD on left ventricular (LV) function and regional norepinephrine gradient after conventional HF pharmacological therapy. Compared with control subjects, animals treated with RD demonstrated an improvement in LV function and reduction of norepinephrine gradients over the myocardium and kidney at 10-week follow-up. Our results demonstrated that effective bilateral RD decrease regional norepinephrine gradients and improve LV contractile function compared with medical therapy alone. Key Words: heart failure, left ventricular function, norepinephrine, renal denervation

Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic inflammation (CRI) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time‐adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C‐reactive protein over 60 months immediately preceding computed tomography coronary angiography. Flow cytometry was performed to measure the osteocalcin‐positive (OCN+) CD34+KDR+ and OCN+CD34+ circulating endothelial progenitor cells (EPCs). Conventional early circulating EPCs CD34+CD133+KDR+ was determined. Coronary calcification was defined as any Agatston score >0. 50% of patients (n=72/145) had coronary calcification. CRI score was associated with presence of coronary calcification (P=0.004) (multivariable‐adjusted: highest versus lowest quartile: odds ratio=5.6 [95% CI 1.1–28.9], P=0.041). Receiver operating characteristics curve revealed divergent behavior of OCN‐expressing circulating EPCs (OCN+CD34+ EPCs: area under the curve=0.60, P=0.034; OCN+CD34+KDR+ EPCs: area under the curve=0.59, P=0.053, positive predictors) versus conventional early EPCs (CD34+CD133+KDR+: area under the curve=0.60, P=0.034, negative predictor) for coronary calcification, which persisted after multivariable adjustments (OCN+CD34+KDR+ [>75th percentile]: odds ratio=7.2 [95% CI 1.8–27.9], P=0.005; OCN+CD34+ EPCs [>75th percentile]: odds ratio=6.0 [95% CI 1.5–23.3], P=0.010; CD34+CD133+KDR+ [>75th percentile: odds ratio=0.3 [95% CI 0.1–1.0], P=0.053). Intriguingly, the CRI score was associated with increased OCN+CD34+ EPCs (highest versus lowest quartile: B=+25.6 [95% CI 0.8–50.5] [×103/mL peripheral blood], P=0.043), but reduced CD34+CD133+KDR+ EPCs (highest versus lowest quartile: B=−16.2 [95% CI −31.5 to −0.9], P=0.038). Conclusions Preceding 60 months of CRI is associated with increased risk of coronary calcification and altered OCN expression in circulating EPCs.

The strong relationship between cigarette smoking and cardiovascular disease (CVD) has been well-documented, but the mechanisms by which smoking increases CVD risk appear to be multifactorial and incompletely understood. Mesenchymal stem cells (MSCs) are regarded as an important candidate for cell-based therapy in CVD. We hypothesized that MSCs derived from induced pluripotent stem cell (iPSC-MSCs) or bone marrow (BM-MSCs) might alleviate cigarette smoke (CS)-induced cardiac injury. This study aimed to investigate the effects of BM-MSCs or iPSC-MSCs on CS-induced changes in serum and cardiac lipid profiles, oxidative stress and inflammation as well as cardiac function in a rat model of passive smoking. Male Sprague-Dawley rats were randomly selected for exposure to either sham air (SA) as control or 4% CS for 1 h per day for 56 days. On day 29 and 43, human adult BM-MSCs, iPSC-MSCs or PBS were administered intravenously to CS-exposed rats. Results from echocardiography, serum and cardiac lipid profiles, cardiac antioxidant capacity, cardiac pro- and anti-inflammatory cytokines and cardiac morphological changes were evaluated at the end of treatment. iPSC-MSC-treated group showed a greater effect in the improvement of CS-induced cardiac dysfunction over BM-MSCs-treated group as shown by increased percentage left ventricular ejection fraction and percentage fractional shortening, in line with the greater reversal of cardiac lipid abnormality. In addition, iPSC-MSCs administration attenuated CS-induced elevation of cardiac pro-inflammatory cytokines as well as restoration of anti-inflammatory cytokines and anti-oxidative markers, leading to ameliorate cardiac morphological abnormalities. These data suggest that iPSC-MSCs on one hand may restore CS-induced cardiac lipid abnormality and on the other hand may attenuate cardiac oxidative stress and inflammation via inhibition of CS-induced NF-κB activation, leading to improvement of cardiac remodeling and dysfunction. Thus, iPSC-MSCs may be a promising candidate in cell-based therapy to prevent cardiac complications in smokers.

Neuromodulation of peripheral nerves with bioelectronic devices is a promising approach for treating a wide range of disorders. Wireless powering could enable long-term operation of these devices, but achieving high performance for miniaturized and deeply placed devices remains a technological challenge. We report the miniaturized integration of a wireless powering system in soft neuromodulation device (15 mm length, 2.7 mm diameter) and demonstrate high performance (about 10%) during in vivo wireless stimulation of the vagus nerve in a porcine animal model. The increased performance is enabled by the generation of a focused and circularly polarized field that enhances efficiency and provides immunity to polarization misalignment. These performance characteristics establish the clinical potential of wireless powering for emerging therapies based on neuromodulation.

BackgroundTricuspid annuloplasty is increasingly performed during left heart valve surgery, but the long‐term clinical outcome postoperatively is not satisfactory. The aim of this study was to determine whether residual pulmonary hypertension (PHT) contributes to the adverse outcome. Methods and ResultsOne‐hundred thirty‐seven patients (age 61±11 years; men, 30%) who underwent tricuspid annuloplasty during left‐side valve surgery were enrolled. The mean pulmonary artery systolic pressure before surgery was 49±13 mm Hg and 32±15 mm Hg following surgery. Patients were divided into 3 groups according to postoperative pulmonary artery systolic pressure: no residual PHT (n=78, 57%), mild residual PHT (n=43, 31%), or significant residual PHT (n=16, 12%). A preoperative larger right ventricular (RV) geometry and tricuspid valve tethering area were associated with mild or significant residual PHT. A total of 24 adverse events (20 heart failures and 4 cardiovascular deaths) occurred during a median follow‐up of 25 months. Kaplan–Meier survival curve demonstrated that patients with significant residual PHT had the highest percentage of adverse events followed by those with mild residual PHT. Patients with no residual PHT had a very low risk of adverse events. Multivariable Cox regression analysis revealed that both mild (hazard ratio=4.94; 95% CI =1.34–18.16; P=0.02) and significant residual PHT (hazard ratio=8.67; 95% CI =2.43–30.98; P

Obesity occurs when overall energy intake surpasses energy expenditure. White adipose tissue is an energy storage site, whereas brown and beige adipose tissues catabolize stored energy to generate heat, which protects against obesity and obesity-associated metabolic disorders. Metabolites are substrates in metabolic reactions that act as signaling molecules, mediating communication between metabolic sites (i.e., adipose tissue, skeletal muscle, and gut microbiota). Although the effects of metabolites from peripheral organs on adipose tissue have been extensively studied, their role in regulating adipocyte thermogenesis requires further investigation. Skeletal muscles and intestinal microorganisms are important metabolic sites in the body, and their metabolites play an important role in obesity. In this review, we consolidated the latest research on skeletal muscles and gut microbiota-derived metabolites that potentially promote adipocyte thermogenesis. Skeletal muscles can release lactate, kynurenic acid, inosine, and β-aminoisobutyric acid, whereas the gut secretes bile acids, butyrate, succinate, cinnabarinic acid, urolithin A, and asparagine. These metabolites function as signaling molecules by interacting with membrane receptors or controlling intracellular enzyme activity. The mechanisms underlying the reciprocal exchange of metabolites between the adipose tissue and other metabolic organs will be a focal point in future studies on obesity. Furthermore, understanding how metabolites regulate adipocyte thermogenesis will provide a basis for establishing new therapeutic targets for obesity. [ABSTRACT FROM AUTHOR]

Abstract Removal of confined space carbon dioxide (CO2) that is in low concentration and with coexisting water is necessary but challenging by physical adsorption method. To make the removal process effective, rendering the nanopore surface hydrophobic to resist water is the popular way. Instead of preventing water from occupying the nanopores, in this work, we propose to utilize the guest water for the spatially selective formation of local surface bound water and further induce the preferential CO2 capture. We observe an anomalous enhancement of CO2 capture performance under humid conditions over carbon nanopores with spatially selective polar sites. It is evidenced that the surface bound water is formed at non-CO2-selective areas of polar carbon nanopores, thus creating additional CO2 trapping sites. This work may inspire the design of environment tolerable materials for molecular separation and purification under harsh conditions.

Abstract Currently, image recognition based on deep neural networks has become the mainstream direction of research; therefore, significant progress has been made in its application in the field of tea detection. Many deep models exhibit high recognition rates in tea leaves detection. However, deploying these models directly on tea-picking equipment in natural environments is impractical; the extremely high parameters and computational complexity of these models make it challenging to perform real-time tea leaves detection. Meanwhile, lightweight models struggle to achieve competitive detection accuracy; therefore, this paper addresses the issue of computational resource constraints in remote mountain areas and proposes Reconstructed Feature and Dual Distillation (RFDD) to enhance the detection capability of lightweight models for tea leaves. In our method, the Reconstructed Feature selectively masks the feature of the student model based on the spatial attention map of the teacher model; it utilizes a generation block to force the student model to generate the teacher’s full feature. The Dual Distillation comprises Decoupled Distillation and Global Distillation. Decoupled Distillation divides the reconstructed feature into foreground and background features based on the Ground-Truth. This compels the student model to allocate different attention to foreground and background, focusing on their critical pixels and channels. However, Decoupled Distillation leads to the loss of relation knowledge between foreground and background pixels. Therefore, we further perform Global Distillation to extract this lost knowledge. Since RFDD only requires loss calculation on feature map, it can be easily applied to various detectors. We conducted experiments on detectors with different frameworks, using a tea dataset collected at the Huangshan Houkui Tea Plantation. The experimental results indicate that, under the guidance of RFDD, the student detectors have achieved performance improvements to varying degrees. For instance, a one-stage detector like RetinaNet (ResNet-50) experienced a 3.14% increase in Average Precision (AP) after RFDD guidance. Similarly, a two-stage model like Faster RCNN (ResNet-50) obtained a 3.53% improvement in AP. This offers promising prospects for lightweight models to efficiently perform real-time tea leaves detection tasks.

Abstract Background Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear. Methods The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro. Results In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice. Conclusions Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases.

Abstract Background Annual epidemics of respiratory syncytial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting in April 2020, RSV seasonal activity declined due to COVID-19 non-pharmaceutical interventions (NPIs) before re-emerging after relaxation of NPIs. We described the unusual patterns of RSV epidemics that occurred in multiple subsequent waves following COVID-19 in different countries and explored factors associated with these patterns. Methods Weekly cases of RSV from twenty-eight countries were obtained from the World Health Organisation and combined with data on country-level characteristics and the stringency of the COVID-19 response. Dynamic time warping and regression were used to cluster time series patterns and describe epidemic characteristics before and after COVID-19 pandemic, and identify related factors. Results While the first wave of RSV epidemics following pandemic suppression exhibited unusual patterns, the second and third waves more closely resembled typical RSV patterns in many countries. Post-pandemic RSV patterns differed in their intensity and/or timing, with several broad patterns across the countries. The onset and peak timings of the first and second waves of RSV epidemics following COVID-19 suppression were earlier in the Southern than Northern Hemisphere. The second wave of RSV epidemics was also earlier with higher population density, and delayed if the intensity of the first wave was higher. More stringent NPIs were associated with lower RSV growth rate and intensity and a shorter gap between the first and second waves. Conclusion Patterns of RSV activity have largely returned to normal following successive waves in the post-pandemic era. Onset and peak timings of future epidemics following disruption of normal RSV dynamics need close monitoring to inform the delivery of preventive and control measures.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is prevalent and increasingly reported. Its diagnosis traditionally follows the Kidney Disease: Improving Global Outcomes (KDIGO) AKI criteria. However, little evidence supports its appropriateness for cardiac surgery patients, particularly regarding the subtle serum creatinine change (ΔSCr) that defines mild AKI. Objectives: The purpose of the study was to investigate the ΔSCr threshold specific to CSA-AKI and compare its impact on CSA-AKI incidence and prognosis with the KDIGO AKI criteria threshold. Methods: A 10-year coronary surgery cohort with serial perioperative SCr measurements was retrospectively analyzed. The relationship and prognostically significant threshold of 48-hour absolute ΔSCr with 30-day mortality were explored using multivariate restricted cubic spline analysis and receiver-operating characteristic curve analysis. AKI incidence and prognostic value were compared between adopting the KDIGO or new thresholds. Results: Among 37,706 patients, 20,290 (53.8%) developed KDIGO-defined AKI. For stage-1 AKI (18,835, 49.9%), the majority (75.2%) were solely attributed to the KDIGO absolute criterion (48-hour ΔSCr ≥0.3 mg/dL). The 48-hour ΔSCr threshold associated with an adjusted odds ratio ≥1.00 for 30-day mortality was 0.549 mg/dL. A similar threshold (0.553 mg/dL) was also identified based on the Youden index cutoff. Applying the 0.55 mg/dL threshold to define stage 1 CSA-AKI, the overall and stage-1 CSA-AKI incidence decreased to 21.0% and 17.2%, with 27.7% of the stage-1 CSA-AKI solely attributed to the new criterion. The prognostic value for AKI defined by this new threshold was significantly higher than the KDIGO criteria. Conclusions: A cardiac surgery-specific ΔSCr threshold in defining AKI was notably higher compared with the current general AKI definition.

Introduction Atrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective in maintaining sinus rhythm in patients with HCM associated with AF. Hybrid ablation, combining a cosmetic approach with a lower rate of AF relapse, lacks comparative studies to verify its efficacy against CA in HCM. This study aims to assess the rhythm control effectiveness of hybrid versus CA in non-obstructive HCM (non-oHCM) patients with AF.Methods/analysis This prospective, multicentre, randomised trial involves a blinded assessment of outcomes in non-oHCM patients with non-paroxysmal AF. Sixty-six candidates from three centres will be randomised 1:1 to either hybrid or CA, including isthmus addressed lesion sets. Participants will be stratified by left atrial (LA) size (LA diameter ≤50 mm or >50 mm). Follow-ups at the 3rd, 6th and 12th months will evaluate the primary endpoint of freedom from documented atrial tachycardia lasting over 30 s within 12 months post-procedure without antiarrhythmic drugs, along with secondary endpoints of all-cause mortality, cardiovascular-related mortality, cerebral stroke, peripheral vascular embolism, heart failure-related rehospitalisation, all-cause rehospitalisation and quality of life assessments.Ethics and disseminationapproval The central ethics committee at Fuwai Hospital has approved the Hypertrophic CardioMyopathy with Atrial Fibrillation trial (approval number: 2022-1736). Results will be disseminated through publications in peer-reviewed journals and presentations at conferences.Trial registration number NCT05610215.

With the massive access to sensing, measuring, and user-side intelligent terminal devices, the functionalities and applications at the edge-side of digital distribution networks have become significantly enriched. However, the limited computation resources of edge computing devices must be utilized efficiently to achieve various functions, presenting challenges to resource scheduling within digital distribution networks. To tackle these challenges, this paper proposes an optimal resource scheduling method for multi-functional edge computing devices. The collaborative processing relationships of multi-functional applications for edge computing devices in digital distribution networks are analyzed to achieve various functions. These applications are further abstracted into computational task models with different characteristics. On this basis, constraints for resource scheduling are established, including the logical relationships between tasks, the multi-core configuration, and the resource limitation of devices. With the proposed scheduling method, computation resources of the edge computing device can be optimally allocated to different tasks, achieving multiple objectives such as reducing the process latency, avoiding task abandonment, and maximizing resource backup. The results of the case study indicate that using the proposed method, the overall task completion time is reduced by 20%, the task processing success rate increases to 95%, and the adequate resource reservation ratio improves to 40%.