Explainable machine learning and online calculators to predict heart failure mortality in intensive care units.

AIMS: This study aims to develop explainable machine learning models and clinical tools for predicting mortality in patients in the intensive care unit (ICU) with heart failure (HF). METHODS: Patients diagnosed with HF who experienced their first ICU stay lasting between 24 h and 28 days were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was all-cause mortality within 28 days. Data analysis was performed using Python and R, with feature selection conducted via least absolute shrinkage and selection operator (LASSO) regression. Fifteen models were evaluated, and the most effective model was rendered explainable through the Shapley additive explanations (SHAP) approach. A nomogram was developed based on logistic regression to facilitate interpretation. For external validation, the eICU database was utilized. RESULTS: After selection, the study included 2343 records, with 1808 surviving and 535 deceased patients. The median age of the study population was 70.00, with ~3/5 males (60.31%). The median length of stay in the ICU was 6.00 days. The median age of the survival group was younger than the non-survival group (69.00 vs. 73.00), and non-survival patients spent longer time in the ICU. Seventy-five features were initially selected, including basic information, vital signs, laboratory tests, haemodynamics and oxygen status. LASSO regression determined the shrinkage parameter α = 0.020, and 44 features were chosen for model construction. The linear discriminant analysis (LDA) model showed the best performance, and the accuracy reached 0.8354 in the training cohort and 0.8563 in the testing cohort. It showed satisfying area under the curve (AUC), recall, precision, F1 score, Cohen's kappa score and Matthew's correlation coefficient. The concordance index (c-index) reached 0.7972 in the training cohort and 0.8125 in the testing cohort. In external validation, the LDA model achieved approximately 0.9 in accuracy, precision, recall and F1 score, with an AUC of 0.79. Univariable analysis was performed in the training cohort. Features that differed significantly between the survival and non-survival groups were subjected to multiple logistic regression. The nomogram built on multiple logistic regression included 14 features and demonstrated excellent performance. The AUC of the nomogram is 0.852 in the training cohort, 0.855 in the internal validation cohort and 0.770 in the external validation cohort. The calibration curve showed good consistency. CONCLUSIONS: The study developed an LDA and a nomogram model for predicting mortality in HF patients in the ICU. The SHAP approach was employed to elucidate the LDA model, enhancing its utility for clinicians. These models were made accessible online for clinical application.

Green Synthesis of Boric Acid Modified Bismuth Based Non-Toxic Perovskite Quantum Dots for Highly Sensitive Detection of Oxytetracycline.

In recent years, perovskite quantum dots (PQDs) have successfully attracted widespread attention due to their excellent optical properties. However, the instability and toxicity problems of perovskite quantum dots are the main obstacles limiting their applications. In this work, bismuth-based perovskite quantum dots were synthesized by a ligand-assisted reprecipitation method, based on which a novel boric acid-functionalized bismuth-based non-toxic perovskite quantum dots fluorescent sensor (Cs3Bi2Br9-APBA) that can be stabilized in the ethanol phase was prepared by a boron affinity technique. Based on the covalent binding interaction of Cs3Bi2Br9-APBA with oxytetracycline (OTC), a highly selective and sensitive method for the detection of OTC was developed, which effectively solved the problems of poor stability and toxicity in the application of perovskite quantum dots. Under the optimal conditions, the fluorescence intensity of the synthesized Cs3Bi2Br9-APBA was linear with the concentration range of 0.1 ∼ 18 µM OTC, and the detection limit could reach 0.0802 µM. The fluorescence detection mechanism was explored and analyzed by spectral overlap analysis, suppression efficiency study of observed and corrected fluorescence, and fluorescence lifetime decay curve fitting, the mechanism of OTC detection by Cs3Bi2Br9-APBA was identified as the inner filter effect (IFE). In addition, the sensor successfully realized the quantitative detection of trace OTC in the environment, and our study provides a new idea for the preparation of green perovskite materials with high stability and selectivity.

Clinical characteristics, diagnosis and short-term outcomes of COVID-19-associated acute myocarditis in China.

AIMS: Acute myocarditis (AM) has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) infection. This study was conducted to present the clinical characteristics, disease courses and short-term prognoses of Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced AM in China, which has been unavailable so far. METHODS AND RESULTS: Data from 28 patients diagnosed with definite COVID-19-associated AM from 6 hospitals in China between 1 December 2022 and 30 June 2023 were collected and analysed. The diagnosis of AM was based on increased troponin level plus typical findings of AM on cardiac magnetic resonance (CMR) imaging and/or endomyocardial biopsy. Among 28 patients with definite COVID-19-related AM, median age was 37 years (Q1-Q3: 22-52) and 53.6% were men. Twenty-three patients occurred within 2 weeks of the onset of COVID-19 infection, 10 patients underwent endomyocardial biopsy and CMR was performed in all patients. Seven (25.0%) patients developed fulminant myocarditis that required inotropic agents or temporary mechanical circulatory support. Of the nine patients (32.1%) with left ventricular ejection fraction (LVEF) below 50% on admission, five had fully recovered LVEF and two demonstrated improvement but to levels below normal at discharge. The comparison of CMR parameters between the baseline and first follow-up showed that ECV was decreased at the first follow-up [28.95 (25.38, 32.55)% vs. 33.65 (31.58, 37.55)%, P = 0.028), while other CMR parameters had no significant changes. Eighteen patients (64.3%) were prescribed with corticosteroids, and seven patients (25.0%) underwent temporary mechanical circulatory support. Only two patients died during hospitalization. CONCLUSIONS: The majority of COVID-19-associated AM occurred within 2 weeks of Omicron variant infection. Fulminant myocarditis complicated by hemodynamic instability requiring temporary mechanical circulatory support was not uncommon. However, short-term outcome was generally good and most AM patients fully recovered.

Recycling of Spent Lithium Iron Phosphate Cathodes: Challenges and Progress.

The number of spent lithium iron phosphate (LiFePO4, LFP) batteries will increase sharply in the next few years, owing to their large market share and development potential. Therefore, recycling of spent LFP batteries is necessary and urgent from both resource utilization and environmental protection standpoints. In this review, the significance of pretreatment for LFP recycling is first underscored, and its technical challenges and recent advancements are presented. Following that, the current recycling methods for spent LFP cathodes are outlined in terms of the respective treating processes, advantages, and disadvantages. Additionally, the preparation methods of LFP cathode material are reviewed to guide the resynthesis of LFP that uses salts obtained from spent LFP, which are beneficial for closed-loop recycling of LFP batteries. Lastly, we explore the future development direction of spent LFP battery recycling, highlighting the importance of technological innovation to advance the sustainable growth of the LFP battery industry.

Synthesis and Kinetics of CO2-Responsive Gemini Surfactants.

Surfactants are hailed as "industrial monosodium glutamate", and are widely used as emulsifiers, demulsifiers, water treatment agents, etc., in the petroleum industry. However, due to the unidirectivity of conventional surfactants, the difficulty in demulsifying petroleum emulsions generated after emulsification with such surfactants increases sharply. Therefore, it is of great significance and application value to design and develop a novel switchable surfactant for oil exploitation. In this study, a CO2-switchable Gemini surfactant of N,N'-dimethyl-N,N'-didodecyl butylene diamine (DMDBA) was synthesized from 1, 4-dibromobutane, dodecylamine, formic acid, and formaldehyde. Then, the synthesized surfactant was structurally characterized by infrared (IR) spectroscopy, hydrogen nuclear magnetic resonance (1H NMR) spectroscopy, and electrospray ionization mass spectrometry (ESI-MS); the changes in conductivity and Zeta potential of DMDBA before and after CO2/N2 injection were also studied. The results show that DMDBA had a good CO2 response and cycle reversibility. The critical micelle concentration (CMC) of cationic surfactant obtained from DMDBA by injecting CO2 was 1.45 × 10-4 mol/L, the surface tension at CMC was 33.4 mN·m-1, and the contact angle with paraffin was less than 90°, indicating that it had a good surface activity and wettability. In addition, the kinetic law of the process of producing surfactant by injecting CO2 was studied, and it was found that the process was a second-order reaction. The influence of temperature and gas velocity on the reaction dynamics was explored. The calculated values from the equation were in good agreement with the measured values, with a correlation coefficient greater than 0.9950. The activation energy measured during the formation of surfactant was Ea = 91.16 kJ/mol.

Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease.

INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

Clinical phenotypes of heart failure patients with supranormal ejection fraction.

AIMS: Heart failure (HF) with supranormal ejection fraction (HFsnEF) represents a distinct clinical entity characterized by limited treatment options and an unfavourable prognosis. Revealing its phenotypic diversity is crucial for understanding disease mechanism and optimizing patient management. We aim to identify phenotypic subgroups in HFsnEF using unsupervised clustering analysis. METHODS: Consecutive hospitalized patients with a diagnosis of HF and a left ventricular ejection fraction ≥65% at baseline echocardiographic evaluations were included for analysis. We conducted unsupervised hierarchical clustering analysis on principal components (HCPC) to identify HFsnEF phenogroups using mixed data variables including demographics, HF duration, vital signs, anthropometrics, smoking/drinking status, HF aetiology, comorbid diseases, laboratory tests and echocardiographic parameters. We then employed decision tree modelling to identify parameters capable of distinguishing distinct clusters. Clinical outcomes, including all-cause death, cardiovascular (CV) death and CV readmission for different clusters, were examined. RESULTS: Three mutually exclusive clusters were identified from the cohort of 221 HFsnEF patients. Cluster 1 (52.5%) predominantly consisted of patients with valvular heart disease, who had larger cardiac chambers and a higher prevalence of atrial fibrillation/atrial flutter. Cluster 2 (26.2%) primarily comprised older ischaemic patients with a higher prevalence of metabolic comorbidities. Cluster 3 (21.3%) were mainly hypertrophic cardiomyopathy patients. Two clinical variables were identified that could be used to group all HFsnEF patients into one of the clusters; they were HF aetiology and comorbid diabetes. During the median follow-up of 53.4 months, 46 (20.8%) all-cause deaths occurred, among them 39 of CV causes. Seventy (31.7%) patients experienced CV readmissions. Three clusters showed distinct differences in mortality outcomes, with Cluster 1 exhibiting the highest risk of all-cause mortality [Cluster 1 vs. Cluster 2: adjusted hazard ratio (aHR) = 3.32, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 3.81, P = 0.036; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.865] and CV mortality (Cluster 1 vs. Cluster 2: aHR = 3.73, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 4.27, P = 0.020; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.870). CV readmission risk was comparable among the three clusters (Cluster 1 vs. Cluster 2: aHR = 0.82, P = 0.590; Cluster 1 vs. Cluster 3: aHR = 1.04, P = 0.900; Cluster 2 vs. Cluster 3: aHR = 1.28, P = 0.580). CONCLUSIONS: In a heterogeneous HFsnEF cohort, three clusters were identified by unsupervised HCPC with distinct clinical characteristics and outcomes.

Factors, Mechanisms, and Kinetics of Spontaneous Emulsification for Heavy Oil-in-Water Emulsions.

In challenging reservoirs where thermal recovery falls short, cold or chemical oil recovery methods are crucial. Spontaneous emulsification (SE), triggered by gentle disturbance, significantly enhances oil recovery. In elucidating SE mechanisms and kinetics, SE processes via direct contact between oil and aqueous phases without stirring were conducted. The effects of temperature, emulsifier concentration, pH, NaCl concentration, and the oil-to-water ratio on SE were investigated through droplet size analysis and turbidity measurements. Furthermore, the emulsification mechanism and derived emulsification kinetics based on turbidity data were obtained. The results underscore the feasibility of SE for oil-water systems, reducing viscous and capillary resistances without agitation. The emulsified oil mass increased with the temperature, pH, and aqueous-to-oil phase volume ratio while decreasing with the NaCl concentration. In this study, for GD-2 crude oil, the optimal emulsified oil amount occurred at a betaine surfactant (BetS-2) emulsifier concentration of 0.45%. Microscopic photo analysis indicated narrow particle size distributions and small droplets, which remained stable over time under various experimental conditions. A combined SE mechanism involving ultralow interfacial tension, interfacial turbulence due to Marangoni effects, and "diffusion and stranding" due to in situ emulsifier hydrophilicity, was speculated. Additionally, an analogous second-order kinetic equation for SE was proposed, indicating exceptional correlation with calculated and experimentally measured values. This study offers theoretical insight for enhancing oil recovery in chemical and cold production of heavy oil in oilfields.

Single-Shot Direct Transmission Terahertz Imaging Based on Intense Broadband Terahertz Radiation.

There are numerous applications of terahertz (THz) imaging in many fields. However, current THz imaging is generally based on scanning technique due to the limited intensity of the THz sources. Thus, it takes a long time to obtain a frame image of the target and cannot meet the requirement of fast THz imaging. Here, we demonstrate a single-shot direct THz imaging strategy based on a broadband intense THz source with a frequency range of 0.1~23 THz and a THz camera with a frequency response range of 1~7 THz. This THz source was generated from the laser-plasma interaction, with its central frequency at ~12 THz. The frame rate of this imaging system was 8.5 frames per second. The imaging resolution reached 146.2 µm. With this imaging system, a single-shot THz image for a target object with a size of more than 7 cm was routinely obtained, showing a potential application for fast THz imaging. Furthermore, we proposed and tested an image enhancement algorithm based on an improved dark channel prior (DCP) theory and multi-scale retinex (MSR) theory to optimize the image brightness, contrast, entropy and peak signal-to-noise ratio (PSNR).

Surface-Functionalized Halo-Tag Gold Nanoprobes for Live-Cell Long-Term Super-Resolution Imaging of Endoplasmic Reticulum Dynamics.

Super-resolution fluorescence microscopy has emerged as a powerful tool for studying endoplasmic reticulum (ER) dynamics in living cells. However, the lack of high-brightness, high-photostability, and stable labeling probes makes long-term super-resolution imaging of the ER still challenging. Herein, we reported a surface-functionalized Halo-tag gold nanofluorescent probe (GNP-Atto565-fR8-CA) that exhibits excellent brightness, photostability, and biocompatibility. GNP-Atto565-fR8-CA can simultaneously load multiple Atto565 dye molecules, significantly improving its brightness. Modifying the cell-penetrating peptide fR8 enables GNP-Atto565-fR8-CA to be efficiently delivered into the cytoplasm, overcoming the challenge of their easy entrapment in vesicles. Fluorescent labeling of ER proteins via Halo tags enables high specificity and stable labeling of GNP-Atto565-fR8-CA to the ER. The SIM super-resolution imaging results showed that GNP-Atto565-fR8-CA can track and observe the long-term dynamic process of the ER, and can also be used for long-term super-resolution imaging of the dynamic interactions between the ER and other organelles. This work offers a practical tool to study live-cell ER ultrastructure and dynamics.

Global trends in heart failure from 1990 to 2019: An age-period-cohort analysis from the Global Burden of Disease study.

AIMS: This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country-specific economic strata. METHODS: This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio-demographic Index (SDI) levels. Through age-period-cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. RESULTS: Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all-age prevalence and YLDs increased over the 30 year span, age-standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was -0.26% and -0.25%, respectively. CONCLUSIONS: This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.

Enhanced Ionic Power Generation via Light-Driven Active Ion Transport Across 2D Semiconductor Heterostructures.

2D semiconductor heterostructures exhibit broad application prospects. However, regular nanochannels of heterostructures rarely caught the researcher's attention. Herein, a metal-organic framework (i.e., Cu3(HHTP)2) and transition metal dichalcogenides (i.e., MoS2)-based multilayer van der Waals heterostructure (i.e., Cu3(HHTP)2/MoS2) realized band alignment-dominated light-driven ion transport and further light-enhanced ionic energy generation. High-density channels of the heterostructure provide high-speed pathways for ion transmembrane transport. Upon light illumination, a net ionic flow occurs at a symmetric concentration, suggesting a directional cationic transport from Cu3(HHTP)2 to MoS2. This is because Cu3(HHTP)2/MoS2 heterostructures containing type-II band alignment can generate photovoltaic motive force through light-induced efficient charge separation to drive ion transport. After introducing into the ionic power generation system, the maximum power density under illumination can achieve notable improvement under different concentration differences. In addition to the photovoltaic motive force, type-II band alignment and material defect capture-induced surface charge increase also raise ion selectivity and flux, greatly facilitating ionic energy generation. This work demonstrates that 2D semiconductor heterostructures with rational band alignment can not only be a potential platform for optimizing light-enhanced ionic energy harvesting but also provide a new thought for biomimetic iontronic devices.

Influence of Ultrafine Fly Ash and Slag Powder on Microstructure and Properties of Magnesium Potassium Phosphate Cement Paste.

This study investigated the influences of ultrafine fly ash (UFA) and ultrafine slag powder (USL) on the compressive strengths, autogenous shrinkage, phase assemblage, and microstructure of magnesium potassium phosphate cement (MKPC). The findings indicate that the aluminosilicate fractions present in both ultrafine fly ash and ultrafine slag participate in the acid-base reaction of the MKPC system, resulting in a preferential formation of irregularly crystalline struvite-K incorporating Al and Si elements or amorphous aluminosilicate phosphate products. UFA addition mitigates early age autogenous shrinkage in MKPC-based materials, whereas USL exacerbates this shrinkage. In terms of the sustained mechanical strength development of the MKPC system, ultrafine fly ash is preferred over ultrafine slag powder. MKPC pastes with ultrafine fly ash show greater compressive strength compared to those with ultrafine slag powder at 180 days due to denser interfaces between the ultrafine fly ash particles and hydration products like struvite-K. The incorporation of 30 wt% ultrafine fly ash enhances compressive strengths across all testing ages.

3D Printed Pedicle Screws with Microarc Oxidation Ceramic Interfaces Enhance Osteointegration and Orthopedic Fixation Feasibility.

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.

Association of potentially inappropriate medications with prognosis among older patients with non-small cell lung cancer.

BACKGROUND: Potentially inappropriate medications (PIMs) are common among older adults with cancer, but their association with overall survival (OS) among non-small cell lung cancer (NSCLC) patients remains unclear. This study aimed to investigate the association between the use of PIMs and OS in patients with NSCLC. METHODS: In this cohort study, we included patients ≥ 65 years with newly diagnosed NSCLC from January 2014 to December 2020. Potentially inappropriate medication (PIM) is defined by the Beers criteria of 2019 at baseline and within six months following the initiation of systemic therapy. Multivariable Cox regression model was built to assess the association between PIMs and overall survival (OS). RESULTS: We finally included 338 patients with a median follow-up for OS of 1777 days. The prevalence of patients receiving at least one PIM was 39.9% (135/338) and 61.2% (71/116) at baseline and after systemic therapy, respectively. The most important factor associated with PIM use was the number of prescribed medications (P < 0.001). Baseline PIM use and PIM after systemic therapy were significantly associated with inferior OS (476 days vs. 844 days, P = 0.044; and 633 days vs. 1600 days, P = 0.007; respectively). In multivariable analysis, both baseline PIM use and PIM after systemic therapy were independent predictors of poor prognosis (adjusted HR, 1.33; 95% CI, 1.01-1.75; P = 0.041; and adjusted HR, 1.86; 95% CI, 1.11-3.14; P = 0.020; respectively). CONCLUSIONS: PIMs are prevalent among older patients with NSCLC and are independent predictors of NSCLC prognosis. There is an urgent need for clinicians to conduct medication reconciliation and appropriate deprescribing for this population, especially for patients with multiple PIMs.

Spectrum mapping technology based creation of a color-contrast reading environment to reach comfort and clarity.

Reading with a bit of yellowish or greenish paper, as compared to white paper, is thought to be more comfortable and friendly, and can help decrease eye fatigue to some degree. In this work, we try to map the light of different colors on a given paper within a region of interest to alter the colors presented by the paper and consequently influence the reading experience. We conducted an ergonomic experiment to study the comfort and clarity under consistent illuminance levels. We adopted 6 color series(red, yellow, green, cyan, blue, and magenta), 5 chroma levels(0, 10, 20, 30, 40), and 4 types of paper with the same hue(yellow) but different lightness(the white, light yellow, yellow, and dark yellow), and conducted pairwise selection experiments within each light color series. Results show that white and low chroma (≈10) color characteristics contribute to comfort, while higher chroma blue(30∼40) color benefits clarity. Referring to white, low chroma greenish and yellowish color characteristics are preferred in terms of comfort and clarity. This work proposes the spectrum mapping technology to endow the paper with new color effects and verifies that although spectrum compositions might differ, people's preferences and comfort perception are consistent with the same object color.

Smooth Muscle Ythdf2 Abrogation Ameliorates Pulmonary Vascular Remodeling by Regulating Myadm Transcript Stability.

BACKGROUND: The N6-methyladenosine (m6A) modification of RNA and its regulators have important roles in the pathogenesis of pulmonary hypertension (PH). Ythdf2 (YTH N6-methyladenosine RNA binding protein 2) is best known for its role in degrading m6A-modified mRNAs such as Hmox1 mRNA, which leads to alternative activation of macrophages in PH. Recent studies have also linked Ythdf2 to the proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its specific roles in PASMCs and downstream targets during the development of PH remain unclear. METHODS: The expression and biological function of Ythdf2 in PASMCs were investigated in human and experimental models of PH. Smooth muscle cell-specific Ythdf2-deficient mice were used to assess the roles of Ythdf2 in PASMCs in vivo. Proteomic analysis, m6A sequencing, and RNA immunoprecipitation analysis were used to screen for potential downstream targets. RESULTS: Ythdf2 was significantly upregulated in human and rodent PH-PASMCs, and smooth muscle cell-specific Ythdf2 deficiency ameliorated PASMC proliferation, right ventricular hypertrophy, pulmonary vascular remodeling, and PH development. Higher expression of Ythdf2 promoted PASMC proliferation and PH by paradoxically stabilizing Myadm mRNA in an m6A-dependent manner. Loss of Ythdf2 decreased the expression of Myadm in PASMCs and pulmonary arteries, both in vitro and in vivo. Additionally, silencing Myadm inhibited the Ythdf2-dependent hyperproliferation of PASMCs by upregulating the cell cycle kinase inhibitor p21. CONCLUSIONS: We have identified a novel mechanism where the increased expression of Ythdf2 stimulates PH-PASMC proliferation through an m6A/Myadm/p21 pathway. Strategies targeting Ythdf2 in PASMCs might be useful additions to the therapeutic approach to PH.

Association of point-of-care testing for sST2 with clinical outcomes in patients hospitalized with heart failure.

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

Prognostic and predictive value of interstitial lung abnormalities and EGFR mutation status in patients with non-small cell lung cancer.

BACKGROUND: To determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC). METHODS: We reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors. RESULTS: EGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861-0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042-0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type. CONCLUSION: Non-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC.