AttriPrompter: Auto-Prompting with Attribute Semantics for Zero-shot Nuclei Detection via Visual-Language Pre-trained Models.

Large-scale visual-language pre-trained models (VLPMs) have demonstrated exceptional performance in downstream object detection through text prompts for natural scenes. However, their application to zero-shot nuclei detection on histopathology images remains relatively unexplored, mainly due to the significant gap between the characteristics of medical images and the weboriginated text-image pairs used for pre-training. This paper aims to investigate the potential of the object-level VLPM, Grounded Language-Image Pre-training (GLIP), for zero-shot nuclei detection. Specifically, we propose an innovative auto-prompting pipeline, named AttriPrompter, comprising attribute generation, attribute augmentation, and relevance sorting, to avoid subjective manual prompt design. AttriPrompter utilizes VLPMs' text-to-image alignment to create semantically rich text prompts, which are then fed into GLIP for initial zero-shot nuclei detection. Additionally, we propose a self-trained knowledge distillation framework, where GLIP serves as the teacher with its initial predictions used as pseudo labels, to address the challenges posed by high nuclei density, including missed detections, false positives, and overlapping instances. Our method exhibits remarkable performance in label-free nuclei detection, out-performing all existing unsupervised methods and demonstrating excellent generality. Notably, this work highlights the astonishing potential of VLPMs pre-trained on natural image-text pairs for downstream tasks in the medical field as well. Code will be released at github.com/AttriPrompter.

Impact of metabolic abnormalities on the association between normal-range urinary albumin-to-creatinine ratio and cardiovascular mortality: evidence from the NHANES 1999-2018.

BACKGROUND: The urinary albumin to creatinine ratio (UACR) is associated with adverse cardiovascular outcomes, even when within the normal range. However, the potential modification of this effect by metabolic abnormalities remains unclear. This study explored whether metabolic abnormalities modify the association between normal-range UACR and cardiovascular mortality. METHODS: This cohort study included 27,298 U.S. adults from the National Health and Nutrition Examination Survey 1999-2018, with mortality follow-up through December 31, 2019. Normal UACR (< 30 mg/g) was considered. Metabolic abnormalities were categorized into three groups based on the number of metabolic abnormality components: metabolic health (0 components), pre-metabolic syndrome (Pre-MetS, 1-2 components), and metabolic syndrome (MetS, 3-5 components). Multivariable Cox proportional hazards regression was used to estimate the association between normal UACR and cardiovascular mortality, stratified by metabolic abnormality groups. RESULTS: Over a median follow-up of 9.67 years, 764 cardiovascular deaths occurred. In the fully adjusted model, higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, but not in metabolically healthy individuals. When UACR was divided into tertiles, the highest tertile was associated with a 60% and 79% higher risk of cardiovascular mortality in the Pre-MetS and MetS groups, respectively, compared with the lowest tertile (Pre-MetS: HR, 1.60 [95% CI: 1.19-2.15]; MetS: HR, 1.79 [95% CI: 1.34-2.41]). CONCLUSION: A higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, underscoring the need for early renal risk management in this population.

TREM2 aggravates sepsis by inhibiting fatty acid oxidation via the SHP1/BTK axis.

Impaired fatty acid oxidation (FAO) and the therapeutic benefits of FAO restoration have been revealed in sepsis. However, the regulatory factors contributing to FAO dysfunction during sepsis remain inadequately clarified. In this study, we identified a subset of lipid-associated macrophages characterized by high expression of trigger receptor expressed on myeloid cells 2 (TREM2) and demonstrated that TREM2 acted as a suppressor of FAO to increase the susceptibility to sepsis. TREM2 expression was markedly up-regulated in sepsis patients and correlated with the severity of sepsis. Knock out of TREM2 in macrophages improved the survival rate and reduced inflammation and organ injuries of sepsis mice. Notably, TREM2-deficient mice exhibited decreased triglyceride accumulation and an enhanced FAO rate. Further observations showed that the blockade of FAO substantially abolished the alleviated symptoms observed in TREM2 knockout mice. Mechanically, we demonstrated that TREM2 interacted with the phosphatase SHP1 to inhibit Bruton tyrosine kinas (BTK)-mediated FAO in sepsis. Our findings expand the understanding of FAO dysfunction in sepsis and reveal TREM2 as a critical regulator of FAO, which may provide a promising target for the clinical treatment of sepsis.

Lipoprotein(a) and High-Sensitivity C-Reactive Protein Compound the Risk of Hypoattenuating Leaflet Thickening After Transcatheter Aortic Valve Replacement.

BACKGROUND: The mechanism for hypoattenuating leaflet thickening (HALT) after transcatheter aortic valve replacement is still not well elucidated, and the role of Lp(a) (lipoprotein[a]) and hs-CRP (high-sensitivity C-reactive protein) has rarely been studied. This study sought to test the hypothesis that the risk of HALT is associated with an elevated level of Lp(a) or hs-CRP. METHODS AND RESULTS: A total of 307 consecutive individuals who underwent a transcatheter aortic valve replacement procedure were included. All patients received their first postoperative computed tomography scans within 12 months, and raw data were analyzed on 3mensio software. HALT was defined as visually identified increased leaflet thickness with typical meniscal appearance and at least 2 different multiplanar reformation projections. Associations of Lp(a) or hs-CRP with the risk of HALT were evaluated using multivariable logistic regression analysis. The incidence of HALT within 12 months after transcatheter aortic valve replacement in this study was 36.2%, and the risk of HALT was associated with higher baseline Lp(a) (the multivariable adjusted odds ratio [OR] for every 10 mg/dL change was 1.18 [95% CI, 1.09-1.29]) and hs-CRP level (the multivariable adjusted OR for every 1 mg/L change was 1.08 [95% CI, 1.00-1.27]). Compared with individuals out of the top 25th percentile for both Lp(a) and hs-CRP, the multivariable adjusted OR for HALT was 4.74 (95% CI, 1.65-14.37) for the top 25th percentile. This result remained consistent after excluding patients receiving anticoagulant therapy. CONCLUSIONS: The top 25th percentile of Lp(a) level (≥40 mg/dL) combined with the top 25th percentile of hs-CRP level (≥3.5 mg/L) conferred a 4.74-fold risk of HALT.

A Photo-Assisted Zinc-Air Battery with MoS2/Oxygen Vacancies Rich TiO2 Heterojunction Photocathode.

Converting solar energy into electrochemical energy is a sustainable strategy, but the design of photo-assisted zinc-air battery (ZAB) with efficient utilization of sunlight faces huge challenges. Herein, a photo-assisted ZAB of a three-electrode system using MoS2/oxygen vacancies-rich TiO2 heterojunction as charge cathode and Fe, N-doped carbon matrix (FeNC) as discharge cathode is constructed, where MoS2 is chosen as solar light-responsive catalytic material and TiO2 acts as electron transport layer and hole blocking layer, arising from a train of thought for efficient charging under sunlight irradiation and light-independent discharging. The introduction of oxygen vacancies in TiO2 facilitates the temporary trapping of carriers and triggers rapid carrier transfer at the interface of the heterojunction, which hinders the recombination of photogenerated holes, thereby facilitating their further participation in the oxygen evolution reaction. Moreover, FeNC exhibits superior oxygen reduction reaction performance due to strong d-π interactions. As a result, the well-built ZABs deliver a low charge voltage (0.71 V) under illumination at 0.1 mA cm-2, and a high power density (167.6 mW cm-2) in dark. This work paves a special way for the development of ZABs by directly harvesting solar energy in charging and efficiently discharging regardless of lighting conditions.

Associations of metabolic syndrome and its components with sarcopenia, and the mediating role of insulin resistance: Findings from NHANES database.

BACKGROUND: To investigate the association between metabolic syndrome (MetS) and its components with sarcopenia, and to explore the extent to which insulin resistance (IR) mediates this association, using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed cross-sectional data from 15,779 adults in the NHANES from 1999 to 2006 and 2011-2018. Multivariable logistic regression models were used to determine the odds ratios (ORs) between MetS, its components, the number of MetS components, and sarcopenia. Mediation analysis was performed to explore the role of the homeostatic model assessment of insulin resistance (HOMA-IR) in MetS and its components-induced sarcopenia. RESULT: In the fully adjusted model, MetS increased the prevalence of sarcopenia by 1.96-fold (95% CI: 1.73-2.22). Among the individual components, central obesity, hypertension, and hyperglycemia were associated with an increased prevalence of sarcopenia. Sarcopenia prevalence also increased linearly with the number of MetS components, with the highest prevalence observed in the presence of all five components (OR: 3.80, 95% CI: 2.79-5.16). Sex-stratified analysis showed that the prevalence of MetS for sarcopenia was higher in males than females. The mediating effects of HOMA-IR on the association between MetS and its components (central obesity, hypertension, and hyperglycemia) with sarcopenia were significant, with mediation effects of 51.7%, 30.7%, 33.2%, and 79.1%, respectively. There was no significant direct association between hyperglycemia and sarcopenia beyond the HOMA-IR pathway. CONCLUSION: MetS and its individual components, excluding hypertriglyceridemia and low high density lipoprotein cholesterol, were associated with a higher prevalence of sarcopenia, especially in males. This association was partially or fully mediated by IR.

The role of residual inflammatory risk and LDL cholesterol in patients with in-stent restenosis undergoing percutaneous coronary intervention.

BACKGROUND: To evaluate the relationships between residual inflammatory risk [assessed by high-sensitivity C-reactive protein (hsCRP)], residual cholesterol risk [assessed by low-density lipoprotein cholesterol (LDL-C)] and clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions. METHODS: Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. RESULTS: During a median follow-up of 36 months, 436 MACEs occurred. Baseline hsCRP was significantly associated with MACE (highest versus lowest quartile, adjusted hazard ratio [aHR] 1.90 [95 % CI, 1.39-2.59]; P < 0.001). By contrast, the baseline LDL-C quartile was not associated with MACE (highest versus lowest quartile, aHR 0.93 [95 % CI, 0.71- 1.22]; P = 0.59). Compared with patients without residual risk (hsCRP <2 mg/L and LDL-C < 70 mg/dL), participants with both residual inflammatory and LDL-C risk (hsCRP ≥2 mg/L and LDL-C ≥ 70 mg/dL) (aHR, 1.39 [95 % CI, 1.06-1.83]; P = 0.02) and those with residual inflammatory risk only (hsCRP ≥2 mg/L and LDL-C < 70 mg/dL) (aHR, 1.34 [95 % CI, 1.01-1.72]; P = 0.04) had significantly higher risks of MACE. CONCLUSIONS: In the current cohort of patients after ISR PCI, inflammation assessed by hsCRP predicted higher risk of adverse clinical outcomes, whereas the level of LDL-C was not associated with adverse prognosis.

miR-155 enhances apoptosis of macrophage through suppressing PI3K-AKT activation in Pseudomonas aeruginosa keratitis.

Keratitis induced by Pseudomonas aeruginosa (P. aeruginosa) is an acute and serious corneal inflammation. As a family of gene regulators, miRNAs play a crucial role in modulating host response after microbial invasion. However, their functions in P. aeruginosa keratitis remain largely unclear. In the present study, we demonstrated that miR-155 expression was significantly increased in macrophages and corneal tissue after P. aeruginosa infection. In vivo studies demonstrated that mice with miR-155 knockdown displayed more resistance to P. aeruginosa keratitis, with a lower bacterial burden. In addition, in vitro and in vivo studies indicated that miR-155 enhanced apoptosis of macrophages after P. aeruginosa infection, and resulted in a susceptible phenotype of P. aeruginosa keratitis. Moreover, miR-155 induced apoptosis through reducing activation of PI3K-Akt signaling pathway. Our data provided evidence of miR-155 mediated apoptosis of macrophage in P. aeruginosa keratitis, which may be an underlying target for the therapy of P. aeruginosa keratitis and other infectious diseases.

Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases.

BACKGRUOUND: Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. METHODS: In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. RESULTS: Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P<0.05). CONCLUSION: The present study indicated that baseline plasma ET-1 levels were associated with the prognosis in prediabetic and diabetic patients with stable CAD, suggesting that ET-1 may be a valuable predictor in CAD patients with impaired glucose metabolism.

Oxygen-doped Carbon Nitrides with Visible Room-temperature Phosphorescence and Invisible Thermal-Stimuli-Responsive Ultraviolet Delayed Fluorescence for Security Applications.

Multi-mode emissive materials with stimuli-responsive producing invisible signals are very attractive for advanced security applications, but development of such materials remains highly challenging. In this work, oxygen-doped carbon nitrides (O-CNs) are prepared via microwave-assisted heating of urea, which exhibit ultraviolet (UV) solid-state fluorescence (SSFL), visible room temperature phosphorescence (RTP) and thermal-stimuli production of invisible UV delayed fluorescence (DF) properties. Further studies confirmed that the SSFL and RTP could be attributed to the introduction of oxygen functional group (e. g., C=O) in the skeleton of O-CNs, thus minimizing the aggregation caused quenching effect, facilitating intersystem crossing, and stabilizing the excited triplet states. The specific thermal-stimuli production of UV DF is deemed to be the relatively large energy gap between ground and excited singlet states as well as an effective triplet-triplet annihilation. Notably, the emission maximum of UV DF locates at ~310 nm with an ultra-narrow full width at half maximum (FWHM) down to 19 nm, so it is completely invisible to the naked eyes, but detectable by a UV camera. To employ the unique characteristics of O-CNs, security protection strategies with superior concealment by virtue of the thermal-stimuli quenching visible RTP and meanwhile producing invisible UV DF are demonstrated.

Physical Frailty and the Risk of Degenerative Valvular Heart Disease.

Background and Objectives: The relationship between physical frailty, age-related conditions, and the incidence of degenerative valvular heart disease (VHD) remains unclear. This study aimed to investigate the potential association between physical frailty and the development of degenerative VHD. Research Design and Methods: Participants from the UK Biobank who were initially free of VHD and heart failure were categorized into 3 groups based on the frailty phenotype: non-frailty, pre-frailty, and frailty. The frailty phenotype was determined by evaluating the following 5 components: weight loss, exhaustion, reduced physical activity, slow gait speed, and low grip strength. The incidence of degenerative VHD, including mitral valve regurgitation (MR), aortic valve regurgitation (AR), and aortic valve stenosis (AS), was assessed using hospital admission or death registries. Results: Among the 331 642 participants, 11 885 (3.6%) exhibited frailty and 143 379 (43.2%) were categorized as pre-frailty. During a median follow-up of 13.8 years, there were 3 684 MR, 1 205 AR, and 3 166 AS events. Compared to non-frailty participants, those with pre-frailty and frailty showed significantly increased risks for MR (hazard ratio [HR], HRpre-frailty:1.19, 95% confidence interval [CI]: 1.11-1.28; HRfrailty: 1.50, 95% CI: 1.30-1.74), AR (HRpre-frailty:1.19, 95% CI: 1.05-1.34; HRfrailty: 1.58, 95% CI: 1.22-2.04), and AS (HRpre-frailty:1.19, 95% CI: 1.11-1.29; HRfrailty: 1.74, 95% CI: 1.51-2.00). Among the 5 components, slow gait speed showed the strongest association with the risk of various types of VHD (HRMR: 1.50, 95% CI: 1.34-1.65; HRAR: 1.50, 95% CI: 1.24-1.80; HRAS: 1.46, 95% CI: 1.32-1.62), followed by exhaustion, low grip strength, and weight loss. Discussion and Implications: Pre-frailty and frailty were associated with a higher risk of all 3 types of degenerative VHD. Early detection and intervention for pre-frailty and frailty in middle-aged and older individuals may assist in preventing or delaying the onset of degenerative VHD.

LncRNA-mRNA co-expression analysis reveals aquaporin-9-promoted neutrophil extracellular trap formation and inflammatory activation in sepsis.

Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection. However, the precise regulatory mechanism of sepsis remains unclear. Using a strand-specific RNA-sequencing, we identified 115 hub differentially expressed long noncoding RNAs (lncRNAs) and 443 mRNAs in septic patients, primarily participated in crucial pathways including neutrophil extracellular trap (NET) formation and toll-like receptor signaling. Notably, NETs related gene aquaporin-9 (AQP9) and its associated lncRNAs exhibited significant upregulation in septic neutrophils. Functional experiments revealed AQP9 interacts with its lncRNAs to augment the formation of neutrophil NETs. In murine sepsis models, AQP9 inhibition with phloretin reduced proinflammatory cytokine production and lung damage. These findings provide crucial insights into the regulatory role of AQP9 in sepsis, unraveling its interaction with associated lncRNAs in transmitting downstream signals, holding promise in informing the development of novel therapeutic strategies aimed at ameliorating the debilitating effects of sepsis.

Galectin-3 induces pathogenic immunosuppressive macrophages through interaction with TREM2 in lung cancer.

BACKGROUND: High infiltration of tumor-associated macrophages (TAMs) is associated with tumor promotion and immunosuppression. The triggering receptor expressed on myeloid cells 2 (TREM2) is emerged as a key immunosuppressive regulator for TAMs, however, how TREM2-expressing TAMs are recruited and what ligands TREM2 interacts with to mediate immunosuppression is unknown. METHODS: Flow cytometry and single-cell RNA sequencing were used to analyze TREM2 expression. Mechanistically, mass spectrometry and immunoprecipitation were employed to identify proteins binding to TREM2. Phagocytosis and co-culture experiments were used to explore the in vitro functions of galectin3-TREM2 pair. Establishment of TREM2f/f-Lyz2-cre mice to validate the role of TREM2 signaling pathway in lung carcinogenesis. GB1107 were further supplemented to validate the therapeutic effect of Galectin3 based on TREM2 signaling regulation. RESULTS: This study identified that abundant TREM2+ macrophages were recruited at the intra-tumor site through the CCL2-CCR2 chemotactic axis. Galectin-3 impaired TREM2-mediated phagocytosis and promoted the conversion of TREM2+ macrophages to immunosuppressive TAMs with attenuated antigen presentation and co-stimulatory functions both in vitro both in vivo, and galectin-3 is a potential ligand for TREM2. Genetic and pharmacological blockade of TREM2 and galectin-3 significantly inhibited lung cancer progression in subcutaneous and orthotopic cancer models by remodeling the tumor immune microenvironment. CONCLUSION: Our findings revealed a previously unknown association between galectin-3 and TREM2 in TAMs of lung cancer, and suggested simultaneous inhibition of galectin3 and TREM2 as potent therapeutic approach for lung cancer therapy.

HSP70 contributes to pathogenesis of fulminant hepatitis induced by coronavirus.

Fulminant viral hepatitis (FH) represents a significant clinical challenge, with its pathogenesis not yet fully elucidated. Heat shock protein (HSP)70, a molecular chaperone protein with a broad range of cytoprotective functions, is upregulated in response to stress. However, the role of HSP70 in FH remains to be investigated. Notably, HSP70 expression is upregulated in the livers of coronavirus-infected mice and patients. Therefore, we investigated the mechanistic role of HSP70 in coronavirus-associated FH pathogenesis. FH was induced in HSP70-deficient (HSP70 KO) mice or in WT mice treated with the HSP70 inhibitor VER155008 when infected with the mouse hepatitis virus strain A59 (MHV-A59). MHV-A59-infected HSP70 KO mice exhibited significantly reduced liver damage and mortality. This effect was attributed to decreased infiltration of monocyte-macrophages and neutrophils in the liver of HSP70 KO mice, resulting in lower levels of inflammatory cytokines such as IL-1ß, TNFα, and IL-6, and a reduced viral load. Moreover, treatment with the HSP70 inhibitor VER155008 protected mice from MHV-A59-induced liver damage and FH mortality. In summary, HSP70 promotes coronavirus-induced FH pathogenesis by enhancing the infiltration of monocyte-macrophages and neutrophils and promoting the secretion of inflammatory cytokines. Therefore, HSP70 is a potential therapeutic target in viral FH intervention.

Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

Comprehensive analysis of the association between triglyceride-glucose index and coronary artery disease severity across different glucose metabolism states: a large-scale cross-sectional study from an Asian cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is associated with the development and prognosis of coronary artery disease (CAD). However, the impact of the TyG index on CAD severity across different glucose metabolism states exhibits significant disparities in previous research. METHODS: This cross-sectional study comprised 10,433 participants from a prospective cohort. Participants were categorized into four groups based on glucose metabolism state: normal glucose regulation (NGR), prediabetes (pre-DM), diabetes mellitus (DM) without insulin prescribed (Rx), and DM with insulin Rx. The TyG index was determined by the following formula: Ln [TG (mg/dL) × FPG (mg/dL) / 2], where TG is triglycerides and FPG is fasting plasm glucose. Statistical methods such as binary logistic regression, interaction analysis, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were employed to analyze the relationship between the TyG index and CAD severity across the entire population and glucose metabolism subgroups. Mediation analysis was conducted to examine the mediating effects of glycated hemoglobin (HbA1c) on these relationships. Sensitivity analysis was performed to ensure the robustness of the findings. RESULTS: Multivariable logistic regression analysis revealed a significant positive association between the TyG index and multi-vessel CAD in the entire population (OR: 1.34; 95% CI: 1.22-1.47 per 1-unit increment). Subgroup analysis demonstrated consistent positive associations in the NGR, pre-DM, and DM non-insulin Rx groups, with the highest OR observed in the NGR group (OR: 1.67; 95% CI: 1.3-2.14 per 1-unit increment). No correlation was found in the DM with insulin Rx subgroup. RCS analyses indicated the distinct dose-response relationships across different glucose metabolism subgroups. Including the TyG index in the established model slightly improved the predictive accuracy, particularly in the NGR group. Mediation analyses showed varying mediating effects of HbA1c among different glucose metabolism subgroups. Sensitivity analysis confirmed the robustness of the aforementioned relationships in the new-onset CAD population and in individuals not using antilipidemic medications. CONCLUSIONS: The TyG index positively associated with CAD severity across all glucose metabolism states, except for individuals receiving insulin treatment. Moreover, it might serve as a supplementary noninvasive predictor of CAD severity in addition to established factors, especially in NGR patients.

Artificial Intelligence in the Screening, Diagnosis, and Management of Aortic Stenosis.

The integration of artificial intelligence (AI) into clinical management of aortic stenosis (AS) has redefined our approach to the assessment and management of this heterogenous valvular heart disease (VHD). While the large-scale early detection of valvular conditions is limited by socioeconomic constraints, AI offers a cost-effective alternative solution for screening by utilizing conventional tools, including electrocardiograms and community-level auscultations, thereby facilitating early detection, prevention, and treatment of AS. Furthermore, AI sheds light on the varied nature of AS, once considered a uniform condition, allowing for more nuanced, data-driven risk assessments and treatment plans. This presents an opportunity to re-evaluate the complexity of AS and to refine treatment using data-driven risk stratification beyond traditional guidelines. AI can be used to support treatment decisions including device selection, procedural techniques, and follow-up surveillance of transcatheter aortic valve replacement (TAVR) in a reproducible manner. While recognizing notable AI achievements, it is important to remember that AI applications in AS still require collaboration with human expertise due to potential limitations such as its susceptibility to bias, and the critical nature of healthcare. This synergy underpins our optimistic view of AI's promising role in the AS clinical pathway.

Image Captioning via Dynamic Path Customization.

This article explores a novel dynamic network for vision and language (V&L) tasks, where the inferring structure is customized on the fly for different inputs. Most previous state-of-the-art (SOTA) approaches are static and handcrafted networks, which not only heavily rely on expert knowledge but also ignore the semantic diversity of input samples, therefore resulting in suboptimal performance. To address these issues, we propose a novel Dynamic Transformer Network (DTNet) for image captioning, which dynamically assigns customized paths to different samples, leading to discriminative yet accurate captions. Specifically, to build a rich routing space and improve routing efficiency, we introduce five types of basic cells and group them into two separate routing spaces according to their operating domains, i.e., spatial and channel. Then, we design a Spatial-Channel Joint Router (SCJR), which endows the model with the capability of path customization based on both spatial and channel information of the input sample. To validate the effectiveness of our proposed DTNet, we conduct extensive experiments on the MS-COCO dataset and achieve new SOTA performance on both the Karpathy split and the online test server. The source code is publicly available at https://github.com/xmu-xiaoma666/DTNet.

The impacts of percutaneous coronary intervention to treat chronic total occlusion of right coronary artery on the 5-year prognosis: A single-centered retrospective study.

BACKGROUND: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study. METHODS: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR). RESULTS: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003). CONCLUSION: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up.