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Abstract Lipoproteins and apolipoproteins are crucial in lipid metabolism, functioning as essential mediators in the transport of cholesterol and triglycerides and being closely related to the pathogenesis of multiple systems, including cardiovascular. Lipoproteins a (Lp(a)), as a unique subclass of lipoproteins, is a low-density lipoprotein(LDL)-like particle with pro-atherosclerotic and pro-inflammatory properties, displaying high heritability. More and more strong evidence points to a possible link between high amounts of Lp(a) and cardiac conditions like atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS), making it a risk factor for heart diseases. In recent years, Lp(a)'s role in other diseases, including neurological disorders and cancer, has been increasingly recognized. Although therapies aimed at low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have achieved significant success, elevated Lp(a) levels remain a significant clinical management problem. Despite the limited efficacy of current lipid-lowering therapies, major clinical advances in new Lp(a)-lowering therapies have significantly advanced the field. This review, grounded in the pathophysiology of lipoproteins, seeks to summarize the wide-ranging connections between lipoproteins (such as LDL-C and HDL-C) and various diseases, alongside the latest clinical developments, special emphasis is placed on the pivotal role of Lp(a) in cardiovascular disease, while also examining its future potential and mechanisms in other conditions. Furthermore, this review discusses Lp(a)-lowering therapies and highlights significant recent advances in emerging treatments, advocates for further exploration into Lp(a)'s pathogenic mechanisms and its potential as a therapeutic target, proposing new secondary prevention strategies for high-risk individuals.

Abstract Ensuring equitable access to health services is crucial for public welfare and social equity, and is a key objective of the United Nations’ Sustainable Development Goals (SDGs). However, existing datasets often define hospital accessibility using travel time to hospitals in geographic dimension only, without considering the supply (hospital capacity) and demand (population distribution) dynamics. To overcome this limitation, we developed and validated a national-scale 1 km map of both hospital travel time and hospital accessibility in China. We used the Gaussian two-step floating catchment area (Ga2SFCA) model to calculate hospital accessibility, incorporating hospital capacity and service population. Various file types and statistical indicators are provided, making the dataset highly accessible for non-specialists. The dataset fills the gap in publicly available nationwide hospital accessibility data for China and can serve as a critical tool in optimizing resource allocation and developing targeted strategies to improve healthcare equity.

Abstract Background Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). Results Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77–0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85–0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82–0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P

Background The incidence of falls among elderly inpatients with psychiatric disorders is on the rise. A lack of adequate physical activity and a sedentary lifestyle have become prevalent among hospitalized elderly patients. Balance training has been demonstrated to be efficacious in reducing the occurrence of falls, yet its application within psychiatric care remains limited. Objective To explore the effect of balance intensive training on balance ability of hospitalized elderly patients with schizophrenia. Methods Seventy-two elderly patients with schizophrenia from a tertiary psychiatric hospital in Jiangxi Province were selected as objects for this research in 2023. Participants were randomly assigned into experimental group (n=36) and control group (n=36). The control group received standard rehabilitation training, whereas the experimental group was provided with a balance-strengthening training program in addition to the standard regimen. The Berg Balance Scale (BBS), the Chinese version of the Barthel Index (BI), and the International Falls Effectiveness Scale (FES-I) were utilized to assess patients at baseline and after 4 and 12 weeks of intervention. Results A total of 62 patients completed the study, with 30 in the experimental group and 32 in the control group. Two-factor repeated measurement ANOVA showed that there was interaction between group and time on BBS and BI scores (P0.05), and time had significant effect on BBS and BI scores (P0.05). The main effects of time on the total score of FES-I and indoor and outdoor activity scores were significant (P

Abstract Background The optimal sedative regime for noninvasive ventilation (NIV) intolerance remains uncertain. The present study aimed to assess the efficacy and safety of remifentanil (REM) compared to dexmedetomidine (DEX) in cardiac surgery patients with moderate-to-severe intolerance to NIV. Methods In this multicenter, prospective, single-blind, randomized controlled study, adult cardiac surgery patients with moderate-to-severe intolerance to NIV were enrolled and randomly assigned to be treated with either REM or DEX for sedation. The status of NIV intolerance was evaluated using a four-point NIV intolerance score at different timepoints within a 72-h period. The primary outcome was the mitigation rate of NIV intolerance following sedation. Results A total of 179 patients were enrolled, with 89 assigned to the REM group and 90 to the DEX group. Baseline characteristics were comparable between the two groups, including NIV intolerance score [3, interquartile range (IQR) 3–3 vs. 3, IQR 3–4, p = 0.180]. The chi-squared test showed that mitigation rate, defined as the proportion of patients who were relieved from their initial intolerance status, was not significant at most timepoints, except for the 15-min timepoint (42% vs. 20%, p = 0.002). However, after considering the time factor, generalized estimating equations showed that the difference was statistically significant, and REM outperformed DEX (odds ratio = 3.31, 95% confidence interval: 1.35–8.12, p = 0.009). Adverse effects, which were not reported in the REM group, were encountered by nine patients in the DEX group, with three instances of bradycardia and six cases of severe hypotension. Secondary outcomes, including NIV failure (5.6% vs. 7.8%, p = 0.564), tracheostomy (1.12% vs. 0%, p = 0.313), ICU LOS (7.7 days, IQR 5.8–12 days vs. 7.0 days, IQR 5–10.6 days, p = 0.219), and in-hospital mortality (1.12% vs. 2.22%, p = 0.567), demonstrated comparability between the two groups. Conclusions In summary, our study demonstrated no significant difference between REM and DEX in the percentage of patients who achieved mitigation among cardiac surgery patients with moderate-to-severe NIV intolerance. However, after considering the time factor, REM was significantly superior to DEX. Trial registration ClinicalTrials.gov (NCT04734418), registered on January 22, 2021. URL of the trial registry record: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AM4S&selectaction=Edit&uid=U00038YX&ts=3&cx=eqn1z0 .

Abstract. Background:. Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. Methods:. In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. Results:. In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962–1.000 in the training cohort and 0.969–0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. Conclusion:. ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Trial Registration:. Chictr.org.cn: ChiCTR2200059599.

Spatial synergy is strengthened integration and connection between cities in a mega-city region, transcending administrative boundaries. The central flow theory suggests that the mega-city regions are formed by the interconnected flows of people across cities, making the spatial synergy can be measured by assessing the aggregation and intensity of flows and interactions between cities and regions. Human mobility data, such as mobile phone data and social media check-ins, enable the tracking of human movements, thus facilitating the transition of central flow theory from theoretical constructs to empirical research. To this end, this study presents an alternative data-driven framework to reveal the multi-scale spatial synergy of mega-city regions from a human mobility perspective. It uncovers homogeneously spatial communities with high inter-city integration using community detection. Strong internal spatial connections of 2.13 billion mobility are filtered using network backbone extraction. An experiment in the Pearl River Delta (PRD), China, demonstrates a multi-scale and multi-core hierarchical spatial synergy in the PRD region. The detailed findings are as follows: (1) Three cities attract the majority of human mobility. Mobility distance is short in urban centers and long in suburban areas. (2) The spatial integration pattern shows the detected communities reveal the hierarchical integration pattern with three main integrated regions: Guangzhou-Foshan-Zhaoqing, Shenzhen-Dongguan-Huizhou, and Zhuhai-Zhongshan-Jiangmen. (3) The spatial connection pattern illustrates the close ties of 9 cities and three core cities, including Guangzhou, Shenzhen, and Foshan. These results provide a human-centric understanding of urban synergy and deeper insights into central flow theory, which supports cooperative development in mega-city regions.

Understanding complex urban systems necessitates untangling the relationships between diverse urban elements such as population, infrastructure, and socioeconomic activities. Scaling laws are basic but effective rules for evaluating a city’s internal growth logic and assessing its efficiency by investigating whether urban indicators scale with population. To date, only limited research has empirically explored the scaling relations between variables of urban mobility in mega-cities at an intra-urban scale of a few meters. Using multiple urban-sensed and human-sensed data, this study proposes a thorough framework for quantifying the scaling laws in a city. To begin, urban mobility networks are built by aggregating population flows using large-scale mobile phone tracking data. To demonstrate the spatiotemporal variability of urban mobility, various network-based mobility measures are proposed. Following that, three different features of urban mobility laws are exposed, explaining spatial agglomeration, spatial hierarchical structures, and the temporal growth process. The scaling correlations between urban indicators pertaining to socioeconomic features and infrastructure and a mobility-population measure are then quantified using multi-sourced urban-sensed data. Applying this framework to the case study of Shenzhen, China revealed (a) spatial travel heterogeneity, hierarchical spatial structures, and mobility growth, and (b) not only a robust sub-linear relationship between infrastructure volume and population, but also a sub-linear relationship for socioeconomic activity. The identified scaling laws, both in terms of mobility measures and urban indicators, provide a multi-faceted portrait of the spatio-temporal variations of urban settings, allowing us to better understand intra-urban developments and, consequently, provide critical policy evaluations and suggestions for improving intra-urban efficiency in the future.

Urban functional zones (UFZs) serve as the spatial carriers embodying urban economic and social activities, thus making the accurate mapping of UFZs imperative for urban planning, management, and sustainable development. Traditional remote sensing-based methods for mapping UFZs primarily capture the physical attributes of ground objects (such as land cover and spatial patterns) while overlooking the inherent social and economic characteristics, as well as the comprehensiveness, heterogeneity, and scale-dependency. With the rapid development of intelligent sensors, the available geospatial big data, reflecting individual human activities, have greatly increased and enable users to analyze UFZs from both physical and socioeconomic aspects. In this study, we provide a comprehensive review of the existing literature on UFZ mapping using remote sensing and geospatial big data. Specifically, this study summarizes the state of the art from three perspectives: spatial analysis units, representation features derived from multi-source data, and the function classification methods of UFZs. Spatial analysis units encompass regular grids, road blocks, image segmentation units, traffic analysis zones, and buildings. Data features consist of the remote sensing image-derived features (such as visual, spatial pattern, and abstract features) and the geospatial big data-derived features (such as spatial, attribute, and temporal features). For function classification, kernel density estimation, cluster analysis, supervised machine learning, probabilistic topic models, and deep learning methods have been applied. Finally, this study discusses the challenges and limitations of UFZ mapping units, the bias issues of geospatial big data, and the integration of remote sensing and geospatial big data. Meanwhile, future opportunities to these issues and the expansion of functions from 2D to 3D are discussed, in order to formulate an enhanced UFZ mapping framework.

Abstract Background No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. Methods In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. Results The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P

Abstract Background Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. Methods Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. Results Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p

Summary: Background: Dual inhibition of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) has been shown to be an effective treatment strategy in many cancers. We sought to determine the objective response rate of combination durvalumab (D) plus tremelimumab (TM) in parallel cohorts of patients with carefully selected rare cancer types in which these agents had not previously been evaluated in phase II trials and for which there was clinical or biological rationale for dual immune checkpoint inhibitor therapy to be active. Methods: We designed a multi-centre, non-blinded, open-label phase II basket trial with each of the following 8 rare cancers considered a separate phase II trial: salivary carcinoma, carcinoma of unknown primary (CUP) with tumour infiltrating lymphocytes and/or expressing PD-L1, mucosal melanoma, acral melanoma, osteosarcoma, undifferentiated pleomorphic sarcoma, clear cell carcinoma of the ovary (CCCO) or squamous cell carcinoma of the anal canal (SCCA). The primary objective was to evaluate the response rate of the combination of D and TM, and the secondary objectives were to evaluate the tolerability and safety of D and TM combination. Eligible patients had advanced, metastatic or recurrent, or unresectable cancer with no known life-prolonging treatment option, age ≥16 years, ECOG performance status 0 or 1. Patients received D (1500 mg IV) + TM (75 mg IV) on Day 1 q4 weeks for 4 cycles followed by D q4 weeks until disease progression. This trial is registered with ClinicalTrials.gov, NCT02879162. Findings: From December 14th, 2016, to August 14, 2019, 140 patients enrolled into seven cohorts. The rare melanoma cohorts were closed due to lack of accrual. Of the 140 patients enrolled, 138 were eligible, 138 were evaluable for toxicity and 128 (91%) were evaluable for response. Durable responses were noted in all cohorts except for osteosarcoma. The overall response rate for eligible patients was 16% (95% CI: 10–23%). The response rates in each cancer cohort were undifferentiated pleomorphic sarcoma 15% (n = 3/20; 95% CI 3–38%), salivary carcinoma 20% (n = 4/20; 95% CI: 6–44%), CUP 17% (n = 3/18; 95% CI 4–41%), SCCA 10% (n = 2/20; 95% CI 12–32%) and CCCO 21% (n = 8/39; 95% CI 9–37%). Grade 3/4 adverse events were rare, where 4 patients experienced grade 4 related events and39 patients experienced grade 3 events. Interpretation: Durvalumab + tremelimumab treatment resulted in meaningful responses in salivary carcinoma and CCCO and deserves further exploration in front-line studies. Funding: AstraZeneca and Canadian Cancer Society.

Abstract After intracerebral hemorrhage (ICH) occurs, the overproduction of reactive oxygen species (ROS) and iron ion overload are the leading causes of secondary damage. Removing excess iron ions and ROS in the meningeal system can effectively alleviate the secondary damage after ICH. This study synthesized ginsenoside Rb1 carbon quantum dots (RBCQDs) using ginsenoside Rb1 and ethylenediamine via a hydrothermal method. RBCQDs exhibit potent capabilities in scavenging ABTS + free radicals and iron ions in solution. After intrathecal injection, the distribution of RBCQDs is predominantly localized in the subarachnoid space. RBCQDs can eliminate ROS and chelate iron ions within the meningeal system. Treatment with RBCQDs significantly improves blood flow in the meningeal system, effectively protecting dying neurons, improving neurological function, and providing a new therapeutic approach for the clinical treatment of ICH.

Abstract. Aging is a significant risk factor for various diseases, including asthma, and it often leads to poorer clinical outcomes, particularly in elderly individuals. It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage, resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases. The effects of aging affect not only the elderly but also those of younger ages, posing significant challenges to global healthcare. Thus, understanding the molecular mechanisms associated with aging in different diseases is essential. One intriguing factor is the aryl hydrocarbon receptor (AhR), which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process. Here, we review the literature on several major hallmarks of aging, including mitochondrial dysfunction, cellular senescence, autophagy, mitophagy, epigenetic alterations, and microbiome disturbances. Moreover, we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures, particularly in relation to the immune system. Furthermore, we explore how aging hallmarks affect clinical characteristics, inflammatory features, exacerbations, and the treatment of asthma. It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

Pansharpening is a process that fuses a multispectral (MS) image with a panchromatic (PAN) image to generate a high-resolution multispectral (HRMS) image. Current methods often overlook scale inconsistency and the correlation within and between a window domain, resulting in suboptimal outcomes. In addition, the use of deep convolutional neural network or transformer often leads to high computational expenses. To address these challenges, we present a lightweight pansharpening network that leverages cross-scale interaction and spatial-spectral enhanced window attention. We first design a spatial-spectral enhanced window transformer (SEWformer) to effectively capture crucial attention within and between interleaved windows. To improve scale consistency, we develop a cross-scale interactive encoder that interacts with different scale attentions derived from the SEWformer. Furthermore, a multiscale residual network with channel attention is constructed as a decoder, which, in conjunction with the encoder, ensures precise detail extraction. The final HRMS image is obtained by combining the extracted details with the UPMS image. Extensive experimental validation on diverse datasets showcases the superiority of our approach over state-of-the-art pansharpening techniques in terms of both performance and efficiency. Compared to the second-best comparison approach, our method achieves significant improvements in the ERGAS metric: 29.6$\%$ on IKONOS, 43.8$\%$ on Pléiades, and 27.6$\%$ on WorldView-3 datasets.

Nonalcoholic fatty liver disease (NAFLD) emerges as the most predominant cause of liver disease, tightly linked to metabolic dysfunction. Bile acids (BAs), initially synthesized from cholesterol in the liver, undergo further metabolism by gut bacteria. Increasingly acknowledged as critical modulators of metabolic processes, BAs have been implicated as important signaling molecules. In this review, we will focus on the mechanism of BAs signaling involved in glucose homeostasis, lipid metabolism, energy expenditure, and immune regulation and summarize their roles in the pathogenesis of NAFLD. Furthermore, gut microbiota dysbiosis plays a key role in the development of NAFLD, and the interactions between BAs and intestinal microbiota is elucidated. In addition, we also discuss potential therapeutic strategies for NAFLD, including drugs targeting BA receptors, modulation of intestinal microbiota, and metabolic surgery.

In order to evaluate the bone density improvement function and safety of the Malugu capsule, rats were divided into sham surgery group, model control group (oophorectomy model), high-dose calcium carbonate group (positive control), and groups with different doses of Malugu capsule (200, 400 and 1200 mg/kg·bw) by 90 days of gavage administration. The bone mineral density of the left femur and the calcium content of the right femur was measured to evaluate the performance of the Malugu capsule in increasing bone density. The acute toxicity test of the Malugu capsule at the dose of 15 g/kg·bw was carried out. Moreover, the genotoxicity test and 4-week feeding test of rats were also performed to evaluate the safety of the Malugu capsule. The results showed that there was no significant difference in body weight of rats among the groups of Malugu capsule treatment compared with the model control group (P>0.05). The bone mineral density of the left femur in the three doses of Malugu capsule groups were 0.6651, 0.6560 and 0.6605 g/cm3, respectively, which was significantly higher than that of 0.6307 g/cm3 (P

Myofibroblastic sarcoma (MS) is a malignant tumor of soft tissue or bone that can occur in children or adults, with a high rate of recurrence and metastasis. We report a case of low-grade malignant MS of the left shoulder, diagnosed based on pathological examination and immunohistochemical staining. However, the patient had unexplained pleural maculopathy. The patient passed away 6 months after the diagnosis of myofibroblast sarcoma due to multiple metastases throughout the sarcoma. Combined with the patient’s history, ancillary findings, and after MDT discussion, the patient was ultimately considered to have a high probability of myofibroblast sarcoma combined with pleural maculopathy. In conclusion, when a patient is diagnosed with myofibroblast sarcoma in combination with pleural macula, in the absence of other causative factors, a deep tissue biopsy of the pleura should be actively performed to confirm the diagnosis.

Abstract Triple‐positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan‐human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin‐dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II–III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%–84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0–I was 75% (95% CI, 46.8%–91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%–98.5%). Mean Ki‐67 level was significantly reduced from 45.0% (95% CI, 19.5%–70.5%) at baseline to 17.2% (95% CI, 0.7%–33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment‐related deaths occurred. This four‐drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

N1-methyladenosine (m1A) modification is a crucial post-transcriptional regulatory mechanism of messenger RNA (mRNA) in living organisms. Few studies have focused on analysis of m1A regulators in lower-grade gliomas (LGG). We employed the Nonnegative Matrix Factorization (NMF) technique on The Cancer Genome Atlas (TCGA) dataset to categorize LGG patients into 2 groups. These groups exhibited substantial disparities in terms of both overall survival (OS) and levels of infiltrating immune cells. We collected the significantly differentially expressed immune-related genes between the 2 clusters, and performed LASSO regression analysis to obtain m1AScores, and established an m1A-related immune-related gene signature (m1A-RIGS). Next, we categorized all patients with LGG into high- and low-risk subgroups, predictive significance of m1AScore was confirmed by conducting univariate/multivariate Cox regression analyses. Additionally, we confirmed variations in immune-related cells and ssGSEA and among the high-/low-risk subcategories in the TCGA dataset. Finally, our study characterized the effects of MSR1 and BIRC5 on LGG cells utilizing Edu assay and flow cytometry to explore the effects of modulation of these genes on glioma. The results of this study suggested that m1A-RIGS may be an excellent prognostic indicator for patients with LGG, and could also promote development of novel immune-based treatment strategies for LGG. Additionally, BIRC5 and MSR1 may be potential therapeutic targets for LGG.

Abstract Background Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking. Methods This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline. Discussion The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery. Trial registration This study has been registered on ClinicalTrials.gov (NCT04734418).

Abstract Background Disco-interaction protein 2 homologue B (DIP2B) plays an important role in DNA methylation. There have been many reports on DIP2B in various diseases, but neither the diagnostic value nor the prognostic value of DIP2B across cancer types has been deeply explored. Methods The expression levels of DIP2B in 33 cancer types were analysed based on data sets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The relationships of DIP2B expression with immune cell infiltration and immune-related gene expression were studied via the CIBERSORT, ESTIMATE and TISIDB tools. Gene set variation analysis (GSVA) was performed to identify pathways related to DIP2B. DIP2B knockdown by siRNA was performed in breast cancer cell lines to investigate the effect on proliferation, apoptosis and migration. The relationships of DIP2B expression with clinicopathological features and prognosis were analysed based on immunohistochemistry. Results DIP2B was highly expressed in 26 of 33 cancer types and was significantly associated with poor overall survival (OS) in breast invasive carcinoma (BRCA), mesothelioma and chromophobe renal cell carcinoma (each P

Abstract Background Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. Methods Liquid chromatography–tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot. Results DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4+ T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4+ T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4+ T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG. Conclusions This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury.

This study presents the results of a comprehensive investigation of a wooden rice bucket made in the 1860s. Macroscopy aspects and microscopic structure were conducted to identify the wood species. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were also adopted to investigate the degradation degree of the rice bucket compared with a new wood sample from the same species. The results of the microscopic identification concluded that the rice bucket was made of Chinese fir (Cunninghamia lanceolata). The XRD pattern indicated that the crystallinity degree of cellulose in the wooden rice bucket decreased to 33.2% from 38.8% (new wood). The FTIR spectra revealed that natural ageing resulted in the degradation of cellulose and hemicellulose, and the change of lignin was not obvious.

Abstract Purpose This national study aimed to investigate the lung ultrasound (LUS) training and practice of respiratory therapists (RTs) in mainland China. Methods A cross-sectional multicenter survey was conducted from May 22, 2021 to August 12, 2021, through online platforms. This survey included RTs in mainland China. The survey was divided into four sections: (1) demographic characteristics and basic information; (2) basic information about LUS training and practice; (3) LUS practice details; and (4) Other ultrasound training and practice. Results A total of 514 responses were received, and 494 valid responses were included in the analysis. 81.2% (401/494) participants’ highest degree of education was a bachelor’s degree, and 43.1% (213/494) participants were at level II in terms of job ranking. 99.2%(490/494) participants agreed that the RTs needed to learn lung ultrasound, but only 12.3% (61/494) participants had received a LUS training course. Further, 66.2% (327/494) experienced participants responded to Sect. 3. Most of RTs used LUS when the patient had hypoxia (265/327, 81%) or dyspnea (260/317, 79.5%); they also used it during spontaneous breathing trial(SBT) (191/327, 58.4%) or in prone position (177/327, 54.1%). The A-line (302/327, 92.4%), B-line (299/327, 91.4%), lung slide (263/327, 80.4%), and bat sign (259/327, 79.2%) were well known as LUS signs. Also, 30.6% (100/327) participants did not use the LUS protocol in their clinical practice, and only 25.4%(83/327) participants said they had used LUS scores. Moreover, 55.7% (182/327) participants frequently changed the respiratory therapy strategy according to LUS results. Conclusions We should improve the number and workplace of RTs in mainland China in the future. We should also standardize the application of LUS practice and training for RTs in mainland China and establish corresponding certification pathways.

Mammalian target of rapamycin (mTOR) signaling pathway is a major regulator of cell proliferation and metabolism, playing significant roles in proliferation, apoptosis, inflammation, and illness. More and more evidences showed that the mTOR signaling pathway affects hair follicle circulation and maintains the stability of hair follicle stem cells. mTOR signaling may be a critical cog in Vitamin D receptor (VDR) deficiency-mediated hair follicle damage and degeneration and related alopecia disorders. This review examines the function of mTOR signaling in hair follicles and hair diseases, and talks about the underlying molecular mechanisms that mTOR signaling regulates.

The argonaute (AGO) family proteins play a crucial role in preventing viral invasions through the plant antiviral RNA silencing pathway, with distinct AGO proteins recruited for specific antiviral mechanisms. Our previous study revealed that Nicotiana benthamiana AGO5 (NbAGO5) expression was significantly upregulated in response to bamboo mosaic virus (BaMV) infection. However, the roles of NbAGO5 in antiviral mechanisms remained to be explored. In this research, we examined the antiviral functions of NbAGO5 in the infections of different viruses. It was found that the accumulation of NbAGO5 was induced not only at the RNA but also at the protein level following the infections of BaMV, potato virus X (PVX), tobacco mosaic virus (TMV), and cucumber mosaic virus (CMV) in N. benthamiana. To explore the antiviral mechanism and regulatory function of NbAGO5, we generated NbAGO5 overexpression (OE-NbAGO5) and knockout (nbago5) transgenic N. benthamiana lines. Our findings reveal that NbAGO5 provides defense against BaMV, PVX, TMV, and a mutant CMV deficient in 2b gene, but not against the wild-type CMV and turnip mosaic virus (TuMV). Through affinity purification and small RNA northern blotting, we demonstrated that NbAGO5 exerts its antiviral function by binding to viral small interfering RNAs (vsiRNAs). Moreover, we observed that CMV 2b and TuMV HC-Pro interact with NbAGO5, triggering its degradation via the 26S proteasome and autophagy pathways, thereby allowing these viruses to overcome NbAGO5-mediated defense. In addition, TuMV HC-Pro provides another line of counter-defense by interfering with vsiRNA binding by NbAGO5. Our study provides further insights into the antiviral RNA interference mechanism and the complex interplay between NbAGO5 and plant viruses.

Hemophagocytic lymphohistiocytosis (HLH) is a severe and life-threatening hyperinflammatory condition characterized by excessive activation of macrophages and T cells and resulted in multi-organ dysfunction. HLH can be a primary disease or secondary to infections, malignancy, and some autoimmune diseases, including adult-onset Still’s disease (AOSD) and systemic lupus erythematosus (SLE). However, it is rare for HLH to occur as a secondary condition to drug-induced lupus erythematosus (DILE). In this report, we present a case of HLH as an unusual complication during SLE treatment in a 31-year-old male patient. The patient initially suffered from active chronic hepatitis B (CHB) and was treated with pegylated INFα-2b (Peg-INFα-2b), tenofovir disoproxil and lamivudine. After 19 months, CHB obtained biochemical and virological response with HBsAg positive to HBsAb. The patient developed fever, headache, and cytopenia after Peg-INFα-2b treatment for 33 months, and laboratory studies revealed that ANA and anti dsDNA were positive. He displayed 5 features meeting the HLH-2004 criteria for diagnosis including fever, pancytopenia, hyperferritinemia, high levels of soluble CD25, and hemophagocytosis on bone marrow biopsy. The patient was initiated with a combination treatment of intravenous methylprednisolone pulse therapy, oral cyclosporine, and etoposide (VP-16), which was followed by a course of oral prednisolone, intravenous cyclophosphamide pulse therapy, and entecavir with complete response. To our knowledge, this is the first report of IFN-α induced SLE complicating with HLH. Physicians should consider the potential autoimmune side effects of IFN-α therapy and be alert to insidious HLH in patients diagnosed with SLE.

Summary: Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6–55.4) and the DCR was 77.8% (90% CI, 56.1–92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0–not reach), and the median PFS was 7.2 months (90% CI, 4.4–13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3–4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Few studies have considered the impacts of sample size and sample ratio of presence and absence points on the results of random forest (RF) testing. We applied this technique for the prediction of the spatial distribution of snail habitats based on a total of 15,000 sample points (5,000 presence samples and 10,000 control points). RF models were built using seven different sample ratios (1:1, 1:2, 1:3, 1:4, 2:1, 3:1, and 4:1) and the optimal ratio was identified via the Area Under the Curve (AUC) statistic. The impact of sample size was compared by RF models under the optimal ratio and the optimal sample size. When the sample size was small, the sampling ratios of 1:1, 1:2 and 1:3 were significantly better than the sample ratios of 4:1 and 3:1 at all four levels of sample sizes (p0.05). The sample ratio of 1:2 appeared to be optimal for a relatively large sample size with the lowest quartile deviation. In addition, increasing the sample size produced a higher AUC and a smaller slope and the most suitable sample size found in this study was 2400 (AUC=0.96). This study provides a feasible idea to select an appropriate sample size and sample ratio for ecological niche modelling (ENM) and also provides a scientific basis for the selection of samples to accurately identify and predict snail habitat distributions.

Screening programmes are important for early diagnosis and treatment of colorectal cancer (CRC) but they are not equally efficient in all locations. Depending on which hospital people belong to, they often are not willing to follow up even after a positive result, resulting in a lower-than-expected overall detection rate. Improved allocation of health resources would increase the program’s efficiency and assist hospital accessibility. A target population exceeding 70,000 people and 18 local hospitals were included in the investigation of an optimization plan based on a locationallocation model. We calculated the hospital service areas and the accessibility for people in communities to CRC-screening hospitals using the Huff Model and the Two-Step Floating Catchment Area (2SFCA) approach. We found that only 28.2% of the residents with initially a positive screening result had chosen followup with colonoscopy and significant geographical differences in spatial accessibility to healthcare services indeed exist. The lowest accessibility was found in the Southeast, including the Zhangjiang, Jichang and Laogang communities with the best accessibility mainly distributed near the city centre of Lujiazui; the latter also had relatively a high level of what is called “ineffective screening” as it represents wasteful resource allocation. It is recommended that Hudong Hospital should be chosen instead of Punan Hospital as the optimization, which can improve the service population of each hospital and the populations served per colonoscope. Based on our results, changes in hospital configuration in colorectal cancer screening programme are needed to achieve adequate population coverage and equitable facility accessibility. Planning of medical services should be based on the spatial distribution trends of the population served.

Higher-order topological superconductors and superfluids have triggered a great deal of interest in recent years. While Majorana zero-energy corner or hinge states have been studied intensively, whether superconductors and superfluids host higher-order topological Bogoliubov excitations with finite energies remain elusive. In this work, we propose that Bogoliubov corner excitations with finite energies can be induced through only mirror-symmetric local potentials from a trivial conventional s -wave superfluid. The topological Bogoliubov excited modes originate from the nontrivial Bogoliubov excitation bands. These modes are protected by the mirror symmetry and are robust against mirror-symmetric perturbations as long as the Bogoliubov energy gap remains open. Our work provides a new insight into higher-order topological excitation states in superfluids and superconductors.

The conronavirus disease 2019 (COVID-19) pandemic exerts a major impact on the world. Understanding the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can help public health personnel to define the prevention and control priorities in practical work. This study summarized the existing literature (update to May 2, 2022) and analyzed and classified the main transmission routes of SARS-CoV-2 based on typical cases and laboratory studies, and proposed relevant prevention and personal protection strategies to provide a basis for more accurate and effective control of SARS-CoV-2 transmission.

Abstract Background Noninvasive ventilation (NIV) has been widely used in critically ill patients after extubation. However, NIV failure is associated with poor outcomes. This study aimed to determine early predictors of NIV failure and to construct an accurate machine-learning model to identify patients at risks of NIV failure after extubation in intensive care units (ICUs). Methods Patients who underwent NIV after extubation in the eICU Collaborative Research Database (eICU-CRD) were included. NIV failure was defined as need for invasive ventilatory support (reintubation or tracheotomy) or death after NIV initiation. A total of 93 clinical and laboratory variables were assessed, and the recursive feature elimination algorithm was used to select key features. Hyperparameter optimization was conducted with an automated machine-learning toolkit called Neural Network Intelligence. A machine-learning model called Categorical Boosting (CatBoost) was developed and compared with nine other models. The model was then prospectively validated among patients enrolled in the Cardiac Surgical ICU of Zhongshan Hospital, Fudan University. Results Of 929 patients included in the eICU-CRD cohort, 248 (26.7%) had NIV failure. The time from extubation to NIV, age, Glasgow Coma Scale (GCS) score, heart rate, respiratory rate, mean blood pressure (MBP), saturation of pulse oxygen (SpO2), temperature, glucose, pH, pressure of oxygen in blood (PaO2), urine output, input volume, ventilation duration, and mean airway pressure were selected. After hyperparameter optimization, our model showed the greatest accuracy in predicting NIV failure (AUROC: 0.872 [95% CI 0.82–0.92]) among all predictive methods in an internal validation. In the prospective validation cohort, our model was also superior (AUROC: 0.846 [95% CI 0.80–0.89]). The sensitivity and specificity in the prediction group is 89% and 75%, while in the validation group they are 90% and 70%. MV duration and respiratory rate were the most important features. Additionally, we developed a web-based tool to help clinicians use our model. Conclusions This study developed and prospectively validated the CatBoost model, which can be used to identify patients who are at risk of NIV failure. Thus, those patients might benefit from early triage and more intensive monitoring. Trial registration: NCT03704324. Registered 1 September 2018, https://register.clinicaltrials.gov .

Abstract Aims Recombinant human brain natriuretic peptide (rh‐BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh‐BNP on cardiac output and venous return function in post‐cardiotomy patients with congestive heart failure (CHF). Methods and results Twenty‐four post‐cardiotomy heart failure patients were enrolled and received a standard loading dose of rh‐BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh‐BNP. The cardiac output and venous return functions were estimated by depicting Frank‐Starling and Guyton curves. After rh‐BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min m2/L, respectively. Meanwhile, cardiac index, stroke volume index, and the cardiac output function curve remained unchanged per se. The decline in Pmsf [−13% (−22% to −8%)] and VRRI [−12% (−25% to −5%)] was much greater than that in the systemic vascular resistance index [−7% (−14% to 0%)]. In the subgroup analysis of reduced ejection fraction (

Abstract Pleural mesothelioma (PM) with pericardial involvement is extremely rare. We now report a rare case of malignant PM with constrictive pericarditis as the first presentation. A 59‐year‐old male diagnosed with constrictive pericarditis underwent pericardiectomy and pericardial pathology revealed mesothelial hyperplasia. Eight months after surgery, the patient was admitted to the hospital with chest tightness and wheezing for 5 days. Computed tomography scan of the chest showed a left lung expansion insufficiency, limited bilateral pleural thickening, pericardial thickening with a small amount of pericardial effusion, and multiple enlarged lymph nodes in the mediastinum, bilateral supraclavicular fossa, bilateral cervical roots, and right axilla. The pleural malignancy should be possibly considered. Pathology after pleural puncture showed malignant PM. Pathology after left supraclavicular lymph node puncture biopsy showed metastatic malignant mesothelioma. The diagnosis of this patient was clear. Although malignant PM rarely involves the pericardial constriction, we cannot ignore the fact that malignant PM involves the pericardium. The patient has been diagnosed with constrictive pericarditis, accompanied by pleural thickening and pleural effusion. Without other pathogenic factors, pleural biopsy should be aggressively performed in patients with constrictive pericarditis to determine the cause.

Timely and accurate local climate zone (LCZ) classification maps are valuable for urban climate studies. The integration of remote sensing and street-level images is promising to produce high-quality LCZ maps, since the former can efficiently capture the information of landscapes on a large-scale while the latter include ground-level details. However, due to their significant differences in spatial distributions and capture views, as well as existing sampling issues of street-level images, how to fuse them effectively is challenging and remains an uncharted research area. To address these issues and fill the gap, this study proposes an effective method to integrate satellite and street-level images for LCZ mapping. Additionally, a simple yet effective street-level image sampling method is proposed. Extensive experiments have been performed and the results demonstrate the effectiveness of the proposed data fusion method and also confirm the usefulness of fusing street-level images with satellite images in enhancing the performance of LCZ mapping. Moreover, the proposed sampling method can increase data representativeness and avoid data redundancy, thus significantly reducing the number of required images while retaining high classification accuracy. To the best of our knowledge, this study is the first attempt to integrate cross-view satellite and street-level images for LCZ mapping. The study and proposed methods can contribute to the development of multi-source data fusion for LCZ map production and further benefit urban climatic research.

Background Both genetic and lifestyle factors contribute to the development of asthma, but whether unfavourable lifestyle is associated with similar increases in risk of developing asthma among individuals with varying genetic risk levels remains unknown. Methods A healthy lifestyle score was constructed using body mass index, smoking status, physical activities and dietary pattern to further categorise into ideal, intermediate and poor groups. Genetic risk of asthma was also categorised as three groups based on the tertiles of polygenic risk score established using 212 reported and verified single-nucleotide polymorphisms of European ancestry in the UK Biobank study. We examined the risk of incident asthma related with each lifestyle level in each genetic risk group by Cox regression models. Results Finally, 327 124 participants without baseline asthma were included, and 157 320 (48.1%) were male. During follow-up, 6238 participants (1.9%) developed asthma. Compared to ideal lifestyle in a low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 3.87 (95% CI, 2.98–5.02) for developing asthma in a high genetic risk group. There was interaction between genetic risk and lifestyle, and the population-attributable fraction of lifestyle and genetic risk were 30.2% and 30.0% respectively. Conclusion In this large contemporary population, lifestyle and genetic factors jointly play critical roles in the development of asthma, and the effect values of lifestyle on incident adult-onset asthma were greater than that of genetic risk. Our findings highlighted the necessity of a comprehensive intervention for the prevention of asthma despite the genetic risk.

Effect of external-recycle operations on the heat-transfer efficiency, specifically for the power-law fluid flowing in double-pass concentric circular heat exchanger under sinusoidal wall fluxes, is investigated theoretically in the developed countries. Given that the fluid is heated twice on both sides of the impermeable sheet, four flow patterns proposed in recycling double-pass operations are expected to make substantial improvements in the performance of heat exchanger device in this study. Theoretical predictions point out that the heat-transfer efficiency increases with the ratio of channel thickness of double-pass concentric circular heat exchanger for all new designs under the same working dimension and the operational condition. The fluid velocity within the double-pass heat exchanger is increased by the fluids flowing through divided subchannels, which contributed to the higher convective heat-transfer efficiency. A simplified mathematical formulation was derived for double-pass concentric circular heat exchangers and would be a significant contribution to analyze heat transfer problems with sinusoidal wall fluxes at boundaries. The results deliver the optimal performance for the proposed four configurations with the use of external recycle compared to those conducted in single-pass, where an impermeable sheet is not inserted. The influences of power-law index and impermeable-sheet position on average Nusselt numbers under various flow patterns are also delineated. The distribution of dimensionless wall temperature was lower at the level of relative smaller thickness of annular channel, and the average Nusselt numbers for four external-recycle configurations and single-pass device were more suitable for operating under same condition. The ratio of the power consumption increment to heat-transfer efficiency enhancement demonstrates the economic feasibility among various configurations of double-pass concentric circular heat exchanger. The results also show that the external-recycle configuration (say Type B in the present study) serves as an important economic advantage in designing concentric circular heat exchangers for heating power-law fluids due to the smaller volumetric flow rate in annular channel with exiting outlet temperature.

Abstract Background Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. Methods Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3–7 days); Stage 3 (8–14 days); Stage 4 (15–21 days); and Stage 5 (22–31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, − 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. Results Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (− 3.27% [95% CI, − 5.86 to − 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P

The CO2 absorption by Monoethanolamine (MEA) solutions as chemical absorption was conducted in the membrane gas absorption module with inserting 3D mini-channel turbulence promoters of the present work. A mathematical modeling of CO2 absorption flux was analyzed by using the chemical absorption theory based on mass-transfer resistances in series. The membrane absorption module with embedding 3D mini-channel turbulence promoters in the current study indicated that the CO2 absorption rate improvement is achieved due to the diminishing concentration polarization effect nearby the membrane surfaces. A simplified regression equation of the average Sherwood number was correlated to express the enhanced mass-transfer coefficient of the CO2 absorption. The experimental results and theoretical predictions showed that the absorption flux improvement was significantly improved with implementing 3D mini-channel turbulence promoters. The experimental results of CO2 absorption fluxes were performed in good agreement with the theoretical predictions in aqueous MEA solutions. A further absorption flux enhancement up to 30.56% was accomplished as compared to the results in the previous work, which the module was inserted the promoter without mini channels. The influences of the MEA absorbent flow rates and inlet CO2 concentrations on the absorption flux and absorption flux improvement are also illustrated under both concurrent- and countercurrent-flow operations.

Instance segmentation has been widely applied in building extraction from remote sensing imagery in recent years, and accurate instance segmentation results are crucial for urban planning, construction and management. However, existing methods for building instance segmentation (BSI) still have room for improvement. To achieve better detection accuracy and superior performance, we introduce a Hybrid Task Cascade (HTC)-based building extraction method, which is more tailored to the characteristics of buildings. As opposed to a cascaded improvement that performs the bounding box and mask branch refinement separately, HTC intertwines them in a joint multilevel process. The experimental results also validate its effectiveness. Our approach achieves better detection accuracy compared to mainstream instance segmentation methods on three different building datasets, yielding outcomes that are more in line with the distinctive characteristics of buildings. Furthermore, we evaluate the effectiveness of each module of the HTC for building extraction and analyze the impact of the detection threshold on the model’s detection accuracy. Finally, we investigate the generalization ability of the proposed model.

Abstract Background Yunnan has the highest rates of HIV in China. Other treatable sexually transmitted infections (STIs) are associated with accelerated HIV transmission and poor ART outcomes, but are only diagnosed by syndromic algorithms. Methods We recruited 406 HIV-positive participants for a cross-sectional study (204 ART-naive and 202 receiving ART). Blood samples and first-voided urine samples were collected. Real-time polymerase chain reaction methods were used for diagnosing Chlamydia trachomatis (CT), Neisseria gonorrhea (NG) and Mycoplasma genitalium (MG). Syphilis and herpes simplex virus type 2 (HSV-2) tests were also performed. Results Among the 406 participants, the overall prevalence of STIs was 47.0% and 45.1% in ART-naive individuals and 49.0% in individuals receiving ART, respectively. The testing frequencies were 11.6% (11.8% vs. 11.4%), 33.2% (29.4% vs. 37.1%), 3.2% (3.4% vs. 3.0%), 2.0% (3.4% vs. 0.5%) and 4.7% (6.4% vs. 3.0%) for active syphilis, HSV-2, CT, NG and MG, respectively. The percentage of multiple infections in both groups was 10.8% (22/204) in ART-naive participants and 9.9% (20/202) in participants receiving ART. Female sex, an age between 18 and 35 years, ever injecting drugs, homosexual or bisexual status, HIV/HBV coinfection, and not receiving ART were identified as risk factors. Self-reported asymptomatic patients were not eliminated from having a laboratory-diagnosed STI. Conclusions The STI prevalence was 47.0% (45.1% vs. 49.0%), and HSV-2, syphilis and MG were the most common STIs in HIV-infected individuals. We found a high prevalence (6.4%) of MG in ART-naive individuals. HIV-positive individuals tend to neglect or hide their genital tract discomfort; thus, we suggest strengthening STI joint screening and treatment services among HIV-infected individuals regardless of whether they describe genital tract discomfort.