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The recombination of charge carriers arriving from the random charge movement in semiconductor photocatalysts greatly limits the practical application of solar-driven H2 evolution. The design of photocatalytic systems with spatially oriented charge-transfer is a promising route to achieve high charge-separation efficiency for photocatalysts. Herein, novel sea-urchin-like ReS2 nanosheet/TiO2 nanoparticle heterojunctions (SURTHs) are constructed. The unique sea-urchin-like structure endows the ReS2 cocatalyst with an unusual charge edge-collection effect, which leads to a significant acceleration of charge separation and transfer, as evidenced by the well-designed selective photodeposition of Pt quantum dots in SURTHs. The markedly improved charge transfer capacity contributes to a high photocatalytic H2 evolution rate of 3.71 mmol h−1 g−1 for SURTHs (an apparent quantum efficiency (AQE) of 16.09%), up to 231.9 times by contrast with that of P25 TiO2. This work would provide a new platform for designing the high-efficiency cocatalyst/photocatalyst system with excellent charge transfer capacity. This work was funded by the China Postdoctoral Science Foundation (pre-station, No. 2019TQ0050), Applied Basic Research Program of Sichuan Province (No. 2020YJ0068), the China Postdoctoral Science Foundation (No. 2020M673186), National Natural Science Foundation of China (No. 22002014), the Applied Basic Research Program of Sichuan Province (No. 2020ZYD014). Thanks for the technical help from Sichuan Province Key Laboratory of Display Science and Technology, State Key Laboratory of Electronic Thin Films and Integrated Devices. Dr. Xiao Luo acknowledges financial support from the National Natural Science Foundation of China (No. 21903084) and Applied Basic Research Program of Sichuan Province (No. 2021YJ0408). Dr. Qing Liu acknowledges financial support from the National Natural Science Foundation of China (No. 52002051) and the Fundamental Research Funds for the Central Universities, SCUT (No. ZYGX2020J009).

Polymer film capacitors are usually limited to relatively low working temperatures due to the large conduction loss of polymer dielectrics under high thermal stress. Here, a polymer dielectric sandwiched by medium-dielectric-constant nanoscale deposition layers is reported, which exhibits significantly suppressed conduction loss and outstanding capacitive performance at high temperatures. A series of deposition materials with distinct band structures and dielectric properties are investigated. It is found that well-balanced bandgap, dielectric constant and electrical conductivity of the nanoscale deposition layer is desirable for suppressing charge injection. The substantial performance improvements are demonstrated to result from the slow decay of barrier height with increasing electric field and the reduced electric field in the deposition layers. The optimized design using a polyetherimide film sandwiched by 150-nm-thick Al2O3 deposition layers gives rise to a concurrent high discharged energy density (2.8 J cm−3) and charge-discharge efficiency (90%) up to 200 °C, which are significantly higher than those of previously reported surface-coated polymer dielectrics, and are even comparable to the maximum values achieved with expensive, less productive solution-based composite approaches. Moreover, the nanoscale coating layer can be fabricated through evaporation deposition techniques, which is accessible with industrial equipment for fast surface deposition of capacitor films

Low-efficiency charge transfer is a critical factor to limit the photocatalytic H2 evolution activity of semiconductor photocatalysts. The interface design is a promising approach to achieve high charge-transfer efficiency for photocatalysts. Herein, a new 2D/2D atomic double-layer WS2/Nb2O5 shell/core photocatalyst (DLWS/Nb2O5) is designed. The atom-resolved HAADF-STEM results unravel the presence of an unusual 2D/2D shell/core interface in DLWS/Nb2O5. Taking advantage of the advanced femtosecond-resolved ultrafast TAS spectra, the average lifetime of charge carriers for DLWS/Nb2O5 (180.97 ps) is considerably shortened as compared to that of Nb2O5 (230.50 ps), strongly indicating that the 2D/2D shell/core interface enables DLWS/Nb2O5 to achieve ultrafast charge transfer from Nb2O5 to atomic double-layer WS2, thus yielding a high photocatalytic H2 evolution rate of 237.6 μmol/h, up to 10.8 times higher than that of pure Nb2O5 nanosheet. This study will open a new window for the development of high-efficient photocatalytic systems through the interface design.

Yao Tong,* Chengrong Bao,* Yi-Qiong Xu,* Lei Tao,* Yao Zhou, Lei Zhuang, Ying Meng, Hui Zhang, Jingjing Xue, Weijun Wang, Lele Zhang, Qingbo Pan, Zhenzhen Shao, Tianran Hu, Qian Guo, Qingsheng Xue, Han Lu, Yan Luo Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Luo; Han Lu Email ly11087@rjh.com.cn; luhan0301@163.comBackground: Acute lung injury (ALI) is a severe respiratory disease with high rates of morbidity and mortality. Many mediators regarding endogenous or exogenous are involved in the pathophysiology of ALI. Here, we have uncovered the involvement of integrins and matrix metalloproteinases, as critical determinants of excessive inflammation and endothelial permeability, in the regulation of ALI.Methods: Inflammatory cytokines were measured by quantitative real-time PCR for mRNA levels and ELISA for secretion levels. Endothelial permeability assay was detected by the passage of rhodamine B isothiocyanate-dextran. Mice lung permeability was assayed by Evans blue albumin (EBA). Western blot was used for protein level measurements. The intracellular reactive oxygen species (ROS) were evaluated using a cell-permeable probe, DCFH-DA. Intratracheal injection of lipopolysaccharide (LPS) into mice was conducted to establish the lung injury model.Results: Exogenous MMP-9 significantly aggravated the inflammatory response and permeability in mouse pulmonary microvascular endothelial cells (PMVECs) treated by LPS, whereas knockdown of MMP-9 exhibited the opposite phenotypes. Knockdown of integrin β 3 or β 5 in LPS-treated PMVECs significantly downregulated MMP-9 expression and decreased inflammatory response and permeability in the presence or absence of exogenous MMP-9. Additionally, the interaction of MMP-9 and integrin β 5 was impaired by a ROS scavenger, which further decreased the pro-inflammatory cytokines production and endothelial leakage in PMVECs subjected to co-treatment (LPS with exogenous MMP-9). In vivo studies, exogenous MMP-9 treatment or knockdown β 3 integrin significantly decreased survival in ALI mice. Notably, knockdown of β 5 integrin alone had no remarkable effect on survival, but which combined with anti-MMP-9 treatment significantly improved the survival by ameliorating excessive lung inflammation and permeability in ALI mice.Conclusion: These findings support the β 3/5 integrin-MMP-9 axis as an endogenous signal that could play a pivotal role in regulating inflammatory response and alveolar-capillary permeability in ALI.Keywords: acute lung injury, endothelial cells, integrin, MMP-9

Stroke, also known as cerebral stroke or cerebrovascular accident, refers to acute ischemic or hemorrhagic encephalopathy caused by a disturbance to cerebral blood flow. Ischemic stroke is the most common type of cerebral stroke, accounting for approximately 80% of the total incidence of clinical stroke. High morbidity, disability, and mortality rates place heavy burdens on the families of patients and society. An increasing number of studies have shown that histone modification plays an important role in the pathogenesis of ischemic stroke, but most studies on histone modification focus on acetylation, and studies on the role of histone methylation in the pathogenesis of ischemic stroke are limited. Here, we review the role of histone methylation and related histone methyltransferase (HMT) inhibitors in the pathogenesis of ischemic stroke and related HMT inhibitors in the treatment of ischemic stroke, which may open up a new avenue to the study of ischemic stroke.

Nowadays, smart meters are deployed in millions of residential households to gain significant insights from fine-grained electricity consumption data. The information extracted from smart meter data enables utilities to identify the socio-demographic characteristics of electricity consumers and then offer them diversified services. Traditionally, this task is implemented in a centralized manner with the assumption that utilities have access to all the smart meter data. However, smart meter data are measured and owned by different retailers in the retail market who may not be willing to share their data. To this end, a distributed electricity consumer characteristics identification method is proposed based on federated learning, which can preserve the privacy of retailers. Specifically, privacy-perseverance principal component analysis (PCA) is exploited to extract features from smart meter data. On this basis, an artificial neural network is trained in a federated manner with three weighted averaging strategies to bridge between smart meter data and the socio-demographic characteristics of consumers. Case studies on the Irish Commission for Energy Regulation (CER) dataset verify that the proposed federated method has comparable performance with the centralized model on both balanced and unbalanced datasets.

Precipitation associated with landfalling tropical cyclones (TCs) poses a significant flood risk to vast regions along and inland of the coasts. Quantifying spatial characteristics of tropical cycl...

Background Although the outcome of breast cancer patients has been improved by advances in early detection, diagnosis and treatment. Due to the heterogeneity of the disease, prognostic assessment still faces challenges. The accumulated data indicate that there is a clear correlation between the tumor immune microenvironment and clinical outcomes. Objective Construct immune-related gene pairs to evaluate the prognosis of breast cancer and patient survival rate. Methods From the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, the Gene expression profiles and clinical data of breast cancer samples were downloaded. TCGA cohort were further divided into a training set (n = 764) and internal validation sets (n = 325). The GEO cohort was analyzed as an external validation cohort (n = 327). In the training set, differently expressed immune-relevant genes (IRGs) were screened firstly, and they were used to construct immune-relevant gene pairs (IRGPs). Then, the prognostic IRGPs were identified via univariate Cox regression analysis. Finally, least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to constituted the IRGP prognostic signature. Kaplan-Meier (KM) survival curves, receiver operating characteristic (ROC) curve analysis, univariate and multivariate Cox regression analysis were used to estimate the predictive value of the IRGP prognostic signature. And the IRGP prognostic signature was validated in the internal validation cohort and external validation cohort. We used gene set enrichment analysis (GSEA) to elucidate the biological functions of the IRGP prognostic signature. Results A total of 474 differently expressed IRGs and 2942 prognostic IRGPs were identified. Finally, we generated a IRGP prognostic signature consisting of 33 IRGPs. Subsequently, the 33 IRGPs grouped BRCA patients into high- and low-risk groups. Kaplan-Meier curves shown a significantly different overall survival in risk groups. Time-dependent ROC curves indicated that the IRGP prognostic signature possessed a high specificity and sensitivity in all the sets. Univariate and multivariate Cox regression analysis showed a statistical significance for the prognostic value of IRGP prognostic signature and the IRGP prognostic signature was a strong independent risk factor. The functional enrichment analysis indicated that low IRGP value was correlated with biological processes related to immune. Immune cell infiltration analysis indicated a significant difference in percentage of M2 macrophages between high- and low-risk groups. Conclusion The 33-IRGPs prognostic signature was developed to provide new insights for the identification of high-risk breast cancer and the evaluation of the possibility of immunotherapy in personalized breast cancer treatment.

Arbutin is a well-known tyrosinase inhibitor that prevents the formation of melanin through the inhibition of tyrosinase. Therefore, it has been widely used as a cosmetic skin-lightening agent. Arbutin is able to scavenge free radicals within cells and previous studies have found that it also exhibited useful activities for the treatment of diuresis, bacterial infections, and cancer, as well as anti-inflammatory and anti-tussive activities. This study analyzed the effects of arbutin on streptozotocin (STZ)-induced diabetes mellitus in a murine model. Healthy male adult C57BL/6 mice (7 weeks old) were randomly allocated into one of the following three groups of six animals: Normal control with no STZ administration, STZ-induced diabetes, and STZ-induced diabetes treated with 0.3 g/kg/day of arbutin. After 12 days, the levels of insulin, C-peptide, and HbA1c were measured in serum, and the expression and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were analyzed in pancreatic tissues by western blotting. Arbutin was found to significantly inhibit the increase in blood glucose and the loss of body weight in diabetic mice. Arbutin increased plasma insulin levels in mice with STZ-induced diabetes, whereas there was no detection of insulin in untreated diabetic mice. In addition, there was an increased expression and activity of SOD, CAT, and GPx in diabetic mice treated with arbutin. This investigation demonstrated that arbutin possesses antioxidant activities and can alleviate symptoms of type-1 diabetes mellitus (T1DM) in mice.

Waveguide technology has great prospects of development in optical see-through near-eye displays with larger field of view, lower thickness and lighter weight than other conventional optical technologies. However, the stray light is usually inevitable in current optical design and manufacturing, causing a poor imaging quality. In this paper, the principle and structures of stray light generation are analyzed, and the causes are discussed by non-sequential ray-tracing with mass precision calculation. From the ray-tracing, the suppression of stray light by optimizing design and manufacturing are achieved. A 2 mm-thickness geometrical waveguide with partially reflective mirror array is designed. The field of view of the optimized geometrical waveguide reaches 47° with 10 mm at exit pupil diameter and 20 mm at eye relief.

Floating photovoltaic (FPV) systems are gaining attention across the world, which make an important contribution to the green energy revolution and diffuse the heated debate on use of land worldwide. Large-scale FPV systems generally deploy crystalline silicon panels that are brittle, heavy and difficult to integrate. Polymer solar cells (PSCs) are one of the emerging PV technologies to date. The potential deployment of PSCs on bodies of water can combine the unique advantages of organic electronics, which allow them to become semitransparent and simultaneously provide controlled shading and green electricity. So far, little attention has been paid to the impacts of FPV technologies on water bodies and their ecosystems. In this study, we propose a new concept of extending semitransparent PSCs (ST-PSCs) to the field of FPV and focus on exploring the environmental impacts and benefits of placing high-performance ST-PSCs on bodies of water. We demonstrate for the first time that the specific transmittance windows with controlled light intensities provided by ST-PSCs can scale up solar energy generation and regulate the growth of four representative microalgae that are widely distributed in diverse aquatic habitats. This work provides insight into environmentally responsible FPV systems for sustainable management of the important primary production in the aquatic ecosystem, instead of simply blocking the sunlight with conventional opaque solar panels.

The fast development in microcontroller unit (MCU) technology has urged continuous decreasing in power consumption by different assignment of operating status among devices. In this work, we focused on the ultra-high Vth (UHVT) transistor and used gate oxide thickness and Vth implantation co-optimization to minimize the gate leakage current towards low-power MCU applications. Based on the 55 nm node, it has been found both theoretically and experimentally that the leakage level has been significantly reduced at different temperature in n-FET, p-FET, data flip-flop (DFF) and inverter (INV). Upon MCU testing under active, sleep and deep sleep modes, obvious decrease in the power consumption is also achieved, providing a promising optimization approach towards a better balance between the speed and power in modern MCU technology.

Asthma is defined as a heterogeneous disease, usually characterized by chronic airway inflammation. Long noncoding RNAs (lncRNAs) play important roles in various biological processes. To know more about the relationships between lncRNAs and asthma, gene microarray analysis was performed to screen differentially expressed lncRNAs between the lung tissue of ovalbumin (OVA) mice and control mice. Further studies showed that downregulating differentially expressed lncRNA-AK149641 by adeno-associated virus 6 (AAV6) in OVA mice inhibited airway inflammation, with improved airway compliance and resistance, diminished infiltration of inflammatory cells, as well as less secretions of mucus, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Moreover, the activity of nuclear factor-kappa B (NF-κB) in the lung tissue was reduced after downregulating lncRNA-AK149641. In conclusion, we proposed that downregulation of lncRNA-AK149641 attenuated the airway inflammatory response in an OVA-induced asthma mouse model, probably in association with modulation of the NF-κB signaling pathway.

Biomedical image segmentation is lately dominated by deep neural networks (DNNs) due to their surpassing expert-level performance. However, the existing DNN models for biomedical image segmentation are generally highly parameterized, which severely impede their deployment on real-time platforms and portable devices. To tackle this difficulty, we propose an evolutionary compression method (ECDNN) to automatically discover efficient DNN architectures for biomedical image segmentation. Different from the existing studies, ECDNN can optimize network loss and number of parameters simultaneously during the evolution, and search for a set of Pareto-optimal solutions in a single run, which is useful for quantifying the tradeoff in satisfying different objectives, and flexible for compressing DNN when preference information is uncertain. In particular, a set of novel genetic operators is proposed for automatically identifying less important filters over the whole network. Moreover, a pruning operator is designed for eliminating convolutional filters from layers involved in feature map concatenation, which is commonly adopted in DNN architectures for capturing multi-level features from biomedical images. Experiments carried out on compressing DNN for retinal vessel and neuronal membrane segmentation tasks show that ECDNN can not only improve the performance without any retraining but also discover efficient network architectures that well maintain the performance. The superiority of the proposed method is further validated by comparison with the state-of-the-art methods.

Dielectric polymers for electrostatic energy storage suffer from low energy density and poor efficiency at elevated temperatures, which constrains their use in the harsh-environment electronic devices, circuits, and systems. Although incorporating insulating, inorganic nanostructures into dielectric polymers promotes the temperature capability, scalable fabrication of high-quality nanocomposite films remains a formidable challenge. Here, we report an all-organic composite comprising dielectric polymers blended with high-electron-affinity molecular semiconductors that exhibits concurrent high energy density (3.0 J cm−3) and high discharge efficiency (90%) up to 200 °C, far outperforming the existing dielectric polymers and polymer nanocomposites. We demonstrate that molecular semiconductors immobilize free electrons via strong electrostatic attraction and impede electric charge injection and transport in dielectric polymers, which leads to the substantial performance improvements. The all-organic composites can be fabricated into large-area and high-quality films with uniform dielectric and capacitive performance, which is crucially important for their successful commercialization and practical application in high-temperature electronics and energy storage devices., Dielectric polymers are widely used in electrostatic energy storage but suffer from low energy density and efficiency at elevated temperatures. Here, the authors show that all-organic composites containing high-electron-affinity molecular semiconductors exhibit excellent capacitive performance at 200 °C.

BACKGROUND Emerging data suggest that in patients with low prostate-specific antigen (PSA) and high Gleason score, prostate cancer (PCa) is more aggressive and more likely to be related to genomic characteristics of neuroendocrinology. However, the evidence for the advantages of local treatment (LT) for these men is lacking. Hence, we investigated survival in men with low-PSA values and high-grade (Gleason score 8-10) PCa according to the treatment of the primary tumor. METHODS Kaplan-Meier survival analysis was applied to analyze the effects on overall survival (OS) and cancer-specific survival (CSS) according to the different treatments of the primary tumor. Multivariable Cox proportional hazards survival regression analysis calculated the CSS after propensity score matching (PSM) in 2 cohorts according to treatment type. The treatment types included the following: (I) LT versus non-LT (NLT) and (II) radical prostatectomy (RP) versus radiotherapy (RT). RESULTS In the Surveillance, Epidemiology, and End Results (SEER) database [2004-2014], we identified 14,208 patients newly diagnosed with low PSA values (10 ng/mL or less), with a Gleason score 8-10, and cT1-4N0M0 prostate adenocarcinoma. After the first PSM, of the 3,512 PCa patients, 1,576 underwent LT and 1,576 underwent NLT. After the second PSM, of the 792 PCa patients, 396 underwent RP, and 396 underwent RT. The 5- and 10-year OS rates for LT vs. NLT patients were 90% and 73% versus 69% and 39%, respectively, while the 5- and 10-year CSS rates for LT vs. NLT patients were 98% and 94% versus 89% and 79%, respectively. Subsequent multivariate survival analysis showed that LT was associated with lower likelihood of PCa mortality relative to NLT [hazard ratio (HR), 0.19; 95% confidence interval (CI), 0.14-0.26, P

This study presents the case of a pregnant woman with antiphospholipid syndrome (APS) who developed septic shock after labor induction. Prolonged coagulation times suggested a hypocoagulable state and contraindication to anticoagulation. Thromboelastography (TEG) similarly indicated hypocoagulation. To exclude the impact of lupus anticoagulant on the coagulation assays, a mixing test of prolonged activated partial thromboplastin times was conducted. The mixing test confirmed that prolongation of coagulation times in vitro was affected by antiphospholipid antibodies (aPL), such as lupus anticoagulant. The patient was administered human immunoglobulin and low-molecular weight heparin to neutralize antibodies and for anticoagulation, respectively. The patient's coagulation state significantly improved. Based on these findings, anesthesiologists and obstetricians should be aware that TEG might not be a reliable method of correcting coagulation parameters in patients with sepsis in the presence of aPL. If necessary, a mixing test can be performed to correctly define a patient's coagulation status.

Driven by greatly increased applications, the optical see-through displays have been developing rapidly in recent decades. As a result, some innovative technologies have emerged toward making the display more compact and lighter with better performance. This paper serves as a systematical review on the advances in developing optical see-through displays, including the physical principles, optical configurations, performance parameters and manufacturing processes. The design principles, current challenges, possible solutions and future potential applications are also discussed in the paper.

Abundant Zhundong coal has the advantages of easy mining and high stability of combustion. However, its high alkali-metal content may cause problems, including furnace slagging and heating surface ...

BACKGROUND The dural puncture epidural (DPE) technique is associated with faster onset than the conventional epidural (EP) technique for labor analgesia. The programmed intermittent epidural bolus (PIEB) mode for maintaining labor analgesia allows for lower anesthetic drug consumption than the continuous epidural infusion (CEI) mode. Whether DPE technique with PIEB mode offers additional benefits for analgesia onset, local anesthetic drug consumption, and side effects versus EP or DPE techniques with CEI mode remains unclear. METHODS Nulliparous women with a visual analog scale (VAS) pain score >50 mm and cervical dilation

In the process of pyrolysis and combustion of coal particles, coal structure evolution will be affected by the ash behavior, which will further affect the char reactivity, especially in the ash melting temperature zone. Lu’an bituminous char and ash samples were prepared at the N2 and air atmospheres respectively across ash melting temperature. A scanning electron microscope (SEM) was used to observe the morphology of char and ash. The specific surface area (SSA) analyzer and thermogravimetric analyzer were respectively adopted to obtain the pore structure characteristics of the coal chars and combustion parameters. Besides, an X-ray diffractometer (XRD) was applied to investigate the graphitization degree of coal chars prepared at different pyrolysis temperatures. The SEM results indicated that the number density and physical dimension of ash spheres exuded from the char particles both gradually increased with the increasing temperature, thus the coalescence of ash spheres could be observed obviously above 1100°C. Some flocculent materials appeared on the surface of the char particles at 1300°C, and it could be speculated that β-Si3N4 was generated in the pyrolysis process under N2. The SSA of the chars decreased with the increasing pyrolysis temperature. Inside the char particles, the micropore area and its proportion in the SSA also declined as the pyrolysis temperature increased. Furthermore, the constantly increasing pyrolysis temperature also caused the reactivity of char decrease, which is consistent with the results obtained by XRD. The higher combustion temperature resulted in the lower porosity and more fragments of the ash.

Background and Aims. Recent epidemiological evidence indicates an association between urolithiasis and atherosclerosis; however, results are incongruous. Our aim is to summarize the association between urolithiasis and arteriosclerosis risk through a detailed meta-analysis. Methods. Relevant studies published before April 2019 were identified by searching OVID, EMBASE, PubMed, Web of Science database, and Cochrane Library. The relationship between urolithiasis and the risk of atherosclerosis was assessed by using odds ratio (OR) values and the corresponding 95% confidence intervals (CIs), and the selection of fixed- or random-effects model based on heterogeneity. Results. The meta-analysis includes 8 observational studies that contained 70,716 samples. Pooled results showed that urolithiasis was associated with an increased adjusted and unadjusted risk estimated for atherosclerosis (P=0.017 and P=0.014, respectively), especially in coronary artery and carotid atherosclerosis, which was associated with the outcome of CV disease. Interestingly, when we merged the data from the vast majority of these samples (n = 65,751/70,716) with serum uric acid levels less than 6.0 mg/dl, it still showed that urolithiasis was associated with a higher risk of atherosclerosis (P<0.001) and with no evidence of heterogeneity (I2 = 0.0%, P=0.697). Furthermore, we also found that renal calculi would increase the risk of moderate or severe atherosclerosis (P<0.001) and recurrent renal calculi were associated with the incidence of atherosclerosis (P=0.007). Conclusions. Urolithiasis is associated with an increased risk for atherosclerosis, especially in coronary artery and carotid atherosclerosis. Urolithiasis may be another potential risk factor of atherosclerosis, which is independent of serum uric acid levels.

Heart failure (HF) is a worldwide disease with high levels of morbidity and mortality. The pathogenesis of HF is complicated and involves imbalances in hormone and electrolyte. B-type natriuretic peptide (BNP) has served as a biomarker of HF severity, and in recent years, it has been used to treat the disease, thanks to its cardio-protective effects, such as diuresis, natriuresis, and vasodilatation. In stage C/D HF, symptoms are severe despite elevated BNP. Disturbances in Ca2+ homeostasis are often a dominating feature of the disease, causing Ca2+-regulatory protein dysfunction, including reduced expression and activity of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a), impaired ryanodine receptors (RYRs) function, intensive Na+-Ca2+ exchanger (NCX), and downregulation of S100A1. The relationship between natriuretic peptides (NPs) and Ca2+-regulatory proteins has been widely studied and represents important mechanisms in the etiology of HF. In this review, we present evidence that BNP may regulate Ca2+-regulatory proteins, in particular, suppressing SERCA2a and S100A1 expression. However, relationships between BNP and other Ca2+-regulatory proteins remain vague.

Deconstructing causal linkages between place attributes and disaster outcomes at coarse scales like zip codes and counties is difficult because heterogeneous socio-economic characteristics ...

The optical see-through near-eye display finds wide applications in various areas such as medical treatment, education, tourism and entertainment. However, the vergence-accommodation conflict (VAC) is an obstacle in developing the optical performance of high quality. Conventional stereoscopic displays provide the virtual images in single focal plane, which cannot satisfy the accommodative perception of human eyes. In this review, we elaborate the causes of VAC, discuss various methodologies to solve the VAC problem and compare the advantages and shortfalls of typical designs. It is concluded that the mandatory software and hardware combining methods for the system is developing trend. A prospect is also given for the future development from the users’ perspective.

The tradeoff between spatial-temporal resolutions and phototoxicity prevents fast 3D super-resolution imaging from living cells, hindering the reveal of the subcellular interactions. Key challenges lie in the quests to optimal excitation and efficient super-resolution. Here, we present a double-ring modulated SPIM design toward an ultrathin uniform light sheet with low side lobes. The combination of IDDR SPIM with our isotropic divide-stages-to-process (ID) networks allows live-cell imaging at isotropic 100 nm resolution with a volume rate up to 17 Hz for thousands of time points.

Traffic prediction with high accuracy has significance towards traffic facilities scheduling, adaptive traffic control logic, even the urban economic development. EV charging station availability prediction is one of the traffic facilities usage forecasting challenges in the urban planning. With the accurate long-term prediction of each EV charging station availability, drivers could schedule the charging activities wisely and avoid range anxiety. Data driven models are commonly applied to deal with the similar questions. However, due to the complex charging station distribution with topological road network structure and time-variant charging station availability, many widely used algorithms, such as recurrent neural network (RNN), could only extract the pure time-series information during the model training. One direct effect is that the prediction accuracy decreases rapidly over time. The Spatial-Temporal Graph Convolutional Network (STGCN) that consists the Graph Convolutional Network (GCN) considering edge connectivity and the Gated Recurrent Unit (GRU) is proposed to process both spatial and temporal dependence of relevant transportation data in this paper. Then, the spatial-temporal model is deployed on a real testing dataset in Dundee City and experiments show a better performance for EV charging station availability forecasting over a long-term period compared with other baselines and the possibility of real-time application.

Recommender systems are powerful tools for information filtering with the ever-growing amount of online data. Despite its success and wide adoption in various web applications and personalized products, many existing recommender systems still suffer from multiple drawbacks such as large amount of unobserved feedback, poor model convergence, etc. These drawbacks of existing work are mainly due to the following two reasons: first, the widely used negative sampling strategy, which treats the unlabeled entries as negative samples, is invalid in real-world settings; second, all training samples are retrieved from the discrete observations, and the underlying true distribution of the users and items is not learned. In this paper, we address these issues by developing a novel framework named PURE, which trains an unbiased positive-unlabeled discriminator to distinguish the true relevant user-item pairs against the ones that are non-relevant, and a generator that learns the underlying user-item continuous distribution. For a comprehensive comparison, we considered 14 popular baselines from 5 different categories of recommendation approaches. Extensive experiments on two public real-world data sets demonstrate that PURE achieves the best performance in terms of 8 ranking based evaluation metrics.

Photons are appealing as flying quantum bits due to their low-noise, long coherence times, light-speed transmission, and ease of manipulation at the single-qubit level using standard optical components such as beam splitters and waveguides. The challenge in optical quantum information processing has been the realization of two-qubit gates for photonic qubits due to the lack of highly efficient optical Kerr nonlinearities at the single-photon level. To date, only probabilistic two-qubit photonic controlled-phase gates based on linear optics and projective measurement using photon detectors have been demonstrated. Here we show that a high-fidelity frequency-encoded deterministic two-photon controlled-phase gate can be achieved by exploiting the strong photon-photon correlation enabled by photonic dimers, and the unique nonreciprocal photonic propagation in chiral quantum nanophotonic systems.

Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by CTA/CTG repeat expansion in the ATXN8/ATXN8OS gene. To analyze the frequency and clinical characteristics of SCA8 patients in mainland China, we combined polymerase chain reaction (PCR) and triplet repeat-primed PCR (TRP-PCR) to detect the CTA/CTG expansion. We studied a cohort of 362 ataxia patients in which the other known causative genes had been previously excluded, from among 1294 index patients. Positive samples were validated by southern blotting. The CTA/CTG expansion was observed in six probands, accounting for approximately 0.46% (6/1294) in all patients, and 1.66% (6/362) in patients without definite molecular diagnosis. Clinically, aside from the typical SCA8 phenotype, some patients carrying the CTA/CTG expansion exhibited the cerebellar form of multisystem atrophy (MSA-C) and ataxia with paroxysmal kinesigenic dyskinesia (PKD). For the first time, we described the PKD phenotype in association with CTA/CTG expansion, suggesting that CTA/CTG expansion might play a role in the pathogenesis of paroxysmal dyskinesia symptoms.

The improvement of excitation efficiency from free space to the longitudinal propagating plasmonic-guided wave attracts growing researchers’ interests recently. In this work, a coupling structure composed of counterpart coaxial split ring resonators and a plasmonic stripe waveguide was proposed to investigate the characteristics of the plasmonic waveguide mode excitation by using finite-difference time-domain (FDTD) method. Results showed that an extremely wide spectrum bandwidth about 930 nm which covered the communication region from 1070 nm to 2 μm was achieved and the excitation efficiencies at resonant wavelengths of 1235 nm and 1636 nm reached 36.1% and 24.5%, respectively. And the coupling wavelength can be modulated by rotating the outer split ring. Our research provides potential applications for next-generation plasmonic integrated chips and functional devices.

The unprecedented amounts of data have catalyzed the trend of combining human insights with machine learning techniques, which facilitate the use of crowdsourcing to enlist label information both effectively and efficiently. One crucial challenge in crowdsourcing is the diverse worker quality, which determines the accuracy of the label information provided by such workers. Motivated by the observations that same set of tasks are typically labeled by the same set of workers, we studied their behaviors across multiple related tasks and proposed an optimization framework for learning from task and worker dual heterogeneity. The proposed method uses a weight tensor to represent the workers’ behaviors across multiple tasks, and seeks to find the optimal solution of the tensor by exploiting its structured information. Then, we propose an iterative algorithm to solve the optimization problem and analyze its computational complexity. To infer the true label of an example, we construct a worker ensemble based on the estimated tensor, whose decisions will be weighted using a set of entropy weight. We also prove that the gradient of the most time-consuming updating block is separable with respect to the workers, which leads to a randomized algorithm with faster speed. Moreover, we extend the learning framework to accommodate to the multi-class setting. Finally, we test the performance of our framework on several datasets, and demonstrate its superiority over state-of-the-art techniques.

Cancer is the leading cause of human deaths in the world and produces serious economic burdens. On September 12, 2018, the academic journal A Cancer Journal for Clinicians published an article about the latest statistics of cancers worldwide, which provided a status report on the global burden of 36 cancers in 185 countries worldwide. Cancer has also become a serious public health problem in China and caused more and more attention of the government and people in recent years. This review analyzes the incidence, mortality and prevalent trend of cancers in China, discusses the reasons behind this status, and reviews the potential countermeasures for cancer prevention and control in China.

Background Previous accidental findings showed that administration of immunoglobulin G (IgG) in treating autoimmune diseases was able to inhibit cancers that happened to grow in these patients. However, such treatment has not been used to treat cancer patients clinically. The mechanism and optimal dosages of this treatment have not been established. Subsequent animal experiments confirmed this effect, but all previous studies in animal models used human IgG which was heterogeneous to the animal hosts and therefore could adversely interfere with the results. Materials and methods We tested different dosages of mouse IgG in treating and preventing three syngeneic cancer types (melanoma, colon cancer, and breast cancer) in three immune potent mouse models. The expression of Ki67, CD34, VEGF, MMPs, and cytokines in tumor tissues were examined with immunohistochemistry or quantitative real-time PCR to evaluate tumor proliferation, vascularization, metastasis, and proinflammatory response in the tumor microenvironment. Results We found that low-dose IgG could effectively inhibit cancer progression, regulate tumor vessel normalization, and prolong survival. Administration of IgG before cancer cell inoculation could also prevent the development of cancer. In addition, IgG caused changes in a number of cytokines and skewed macrophage polarization toward M1-like phenotype, characterized by proinflammatory activity and inhibition of proliferation of cancer cells. Conclusion Our findings suggest that nonspecific IgG at low dosages could be a promising candidate for cancer prevention and treatment.

Silicosis resulting from silica exposure is a global occupational disease characterized by severe pathological changes in progressive pulmonary fibrosis. Previous evidence has indicated that dysbiosis of the gut microbiota occurs after environmental dust exposure and is associated with certain diseases. The aims of this study are to elucidate the compositional and functional characteristics of the gut microbiota in early-stage silicosis and to understand their influence on pulmonary fibrosis. We investigated the gut microbial composition of fecal samples from 18 patients and 21 healthy subjects using 16S rRNA gene sequencing technology. Compared with the healthy subjects, reductions in the levels of Firmicutes and Actinobacteria were noted in patients with silicosis and progressive pulmonary fibrosis, as well as lower levels of Devosia, Clostridiales, AlloprevotellaandRikenellaceae_RC9. Lachnospiraceae and Lachnoclostridium levels were increased in patients with silicosis. GOC and KEGG analyses were used to predict that certain bacteria taxa play critical roles in the development of pulmonary fibrosis, including posttranslational modification, amino acid transport and metabolism, nucleotide transport and metabolism, and ribosomal structure and biogenesis. KEGG analysis showed that certain taxa participate in various roles including cancer, endocrine metabolism, immune system, signaling molecules and interaction, and transcription. Collectively, in this pilot study, microbiota changes have been represented in the gut of patients with silicosis. Although this change in gut microbiota have been represented, caution is needed when interpreting the findings since this is observational finding, not necessarily causative. More studies should be performed in the expanding population to be verified and more studies underlying biological mechanisms for better understanding the relationship between gut microbiota and development of pulmonary fibrosis in patients with silicosis.

This article establishes a dynamic game with incomplete information to theoretically analyze the influence mechanism of information disclosure on systemic risk in the presence of a deposit insuranc...

Objective. To investigate the intervention effect and functioning mechanism of citrus alkaline extract (CAE) on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods. 42 C57BL/6 male mice were assigned randomly to the normal group, model group, low (16mg/kg), medial (32mg/kg) and high (64mg/kg) CAE dosage groups, prednisone group (6mg/kg), and pirfenidone group (100mg/kg), respectively. One day after model construction, intragastric administration was applied to the mice once a day for 28 days and then killed. Body weights of mice were recorded. Their pulmonary tissues were subjected to HE staining and Masson’s staining and then their degree of pulmonary alveolitis as well as pulmonary fibrosis was scored. Contents of hydroxyproline (HYP) and prostaglandin E2 (PGE2) in pulmonary tissues and levels of interleukin-17 (IL-17) in serum and bronchoalveolar lavage fluid (BALF) were determined by ELISA method. Expression of collagen I, collagen III, and Prosurfactant protein C (Pro-SPC) proteins in pulmonary tissue were measured immunohistochemically and that of nuclear transcription factor κB (NF-κB) and vimentin was determined by the immunofluorescence method. Apoptosis of pulmonary tissue was tested by the Tunel staining method, while the expression of MAPK-related protein was recorded by Western Blot assay. Results. After CAE treatment, the body weight, PGE2 level, and Pro-SPC protein expression of pulmonary fibrosis mice were increased, while the score of pulmonary alveolitis and pulmonary fibrosis, levels of HYP and cell apoptosis, IL-17 contents of serum and BALF in pulmonary tissues, and expression of collagen I, collagen III, vimentin, NF-κB, and p-p38 were reduced. Conclusion. CAE effectively delayed the progression of BLM-induced pulmonary fibrosis in pulmonary fibrosis mice and a possible mechanism is the inhibition of cell apoptosis of NF-κB/p38-mediated signaling pathway.

Objective: To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China. Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all α- and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of α-thalassemia and 41/42 (–CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.

BACKGROUND Severe adenovirus pneumonia (SAP) of children is prone to multi-system complications, has the high mortality rate and high incidence of sequelae. Severity prediction can facilitate an adequate individualized treatment plan. Our study try to develop and evaluate a predictive nomogram for children with SAP. METHODS An observational study was designed and performed retrospectively. The data were categorized as training and validation datasets using the method of credible random split-sample (split ratio =0.7:0.3). The predictors were selected using Lasso (least absolute shrinkage and selection operator) logistic regression and the nomogram was developed. Nomogram discrimination was assessed using the receiver operating characteristic (ROC) curve, and the prediction accuracy was evaluated using a calibration curve. The nomogram was also evaluated for clinical effectiveness by the decision curve analysis (DCA). A P value of

Metastatic lesions of the pancreas are uncommon. The incidence of pancreatic involvement with squamous cell carcinoma is the lowest among the different histological subtypes of lung cancer. We present the clinical data, pathological findings, and imaging features of two cases of pancreatic metastasis from squamous cell lung cancer with a literature review. A 75-year-old man and a 67-year-old man were both diagnosed with metastatic pancreatic tumors from squamous cell lung cancer during a multidisciplinary team discussion. Both patients were misdiagnosed as having a neuroendocrine tumor of the pancreas by imaging examination before surgery. Squamous cell lung cancer metastasis to the pancreas is extremely rare, and the atypical clinical and radiological presentations make it difficult to distinguish metastatic tumors from primary pancreatic tumors.

Neural networks have been demonstrated to be trainable even with hundreds of layers, which exhibit remarkable improvement on expressive power and provide significant performance gains in a variety of tasks. However, the prohibitive computational cost has become a severe challenge for deploying them on resource-constrained platforms. Meanwhile, widely adopted deep neural network architectures, for example, ResNets or DenseNets, are manually crafted on benchmark datasets, which hamper their generalization ability to other domains. To cope with these issues, we propose an evolutionary algorithm-based method for shallowing deep neural networks (DNNs) at block levels, which is termed as ESNB. Different from existing studies, ESNB utilizes the ensemble view of block-wise DNNs and employs the multiobjective optimization paradigm to reduce the number of blocks while avoiding performance degradation. It automatically discovers shallower network architectures by pruning less informative blocks, and employs knowledge distillation to recover the performance. Moreover, a novel prior knowledge incorporation strategy is proposed to improve the exploration ability of the evolutionary search process, and a correctness-aware knowledge distillation strategy is designed for better knowledge transferring. Experimental results show that the proposed method can effectively accelerate the inference of DNNs while achieving superior performance when compared with the state-of-the-art competing methods.

Background Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in men. Alpha-blockers are widely used as first-line therapy for men with LUTS secondary to BPO, but up to one third of men report no improvement in their LUTS after taking alpha-blockers. Anticholinergics used in addition to alpha-blockers may help improve symptoms but it is uncertain how effective they are. OBJECTIVES: To assess the effects of combination therapy with anticholinergics and alpha-blockers in men with LUTS related to BPO. Search methods We performed a comprehensive search of medical literature, including the Cochrane Library, MEDLINE, Embase, and trials registries, with no restrictions on the language of publication or publication status. The date of the latest search was 7 August 2020. Selection criteria We included randomized controlled trials. Inclusion criteria were men with LUTS secondary to BPO, ages 40 years or older, and a total International Prostate Symptom Score of 8 or greater. We excluded trials of men with a known neurogenic bladder due to spinal cord injury, multiple sclerosis, or central nervous system disease, and those examining medical therapy for men who were treated with surgery for BPO. We performed three comparisons: combination therapy versus placebo, combination therapy versus alpha-blockers monotherapy, and combination therapy versus anticholinergics monotherapy. Data collection and analysis Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE approach to rate the certainty of evidence. Main results We included 23 studies with 6285 randomized men across three comparisons. The mean age of participants ranged from 54.4 years to 73.9 years (overall mean age 65.7 years). Of the included studies, 12 were conducted with a single-center setting, while 11 used a multi-center setting. We only found short-term effect (12 weeks to 12 months) of combination therapy based on available evidence. Combination therapy versus placebo: based on five studies with 2369 randomized participants, combination therapy may result in little or no difference in urologic symptom scores (mean difference (MD) -2.73, 95% confidence interval (CI) -5.55 to 0.08; low-certainty evidence). We are very uncertain about the effect of combination therapy on quality of life (QoL) (MD -0.97, 95% CI -2.11 to 0.16; very low-certainty evidence). Combination therapy likely increases adverse events (risk ratio (RR) 1.24, 95% CI 1.04 to 1.47; moderate-certainty evidence); based on 252 adverse events per 1000 participants in the placebo group, this corresponds to 61 more adverse events (95% CI 10 more to 119 more) per 1000 participants treated with combination therapy. Combination therapy versus alpha-blockers alone: based on 22 studies with 4904 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -2.04, 95% CI -3.56 to -0.52; very low-certainty evidence) and QoL (MD -0.71, 95% CI -1.03 to -0.38; very low-certainty evidence). Combination therapy may result in little or no difference in adverse events rate (RR 1.10, 95% CI 0.90 to 1.34; low-certainty evidence); based on 228 adverse events per 1000 participants in the alpha-blocker group, this corresponds to 23 more adverse events (95% CI 23 fewer to 78 more) per 1000 participants treated with combination therapy. Combination therapy compared to anticholinergics alone: based on three studies with 1218 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -3.71, 95% CI -9.41 to 1.98; very low-certainty evidence). Combination therapy may result in an improvement in QoL (MD -1.49, 95% CI -1.88 to -1.11; low-certainty evidence). Combination therapy likely results in little to no difference in adverse events (RR 1.26, 95% CI 0.81 to 1.95; moderate-certainty evidence); based on 115 adverse events per 1000 participants in the anticholinergic alone group, this corresponds to 4 fewer adverse events (95% CI 7 fewer to 13 more) per 1000 participants treated with combination therapy. Authors' conclusions Based on the findings of the review, combination therapy with anticholinergics and alpha-blockers are associated with little or uncertain effects on urologic symptom scores compared to placebo, alpha-blockers, or anticholinergics monotherapy. However, combination therapy may result in an improvement in quality of life compared to anticholinergics monotherapy, but an uncertain effect compared to placebo, or alpha-blockers. Combination therapy likely increases adverse events compared to placebo, but not compared to alpha-blockers or anticholinergics monotherapy. The findings of this review were limited by study limitations, inconsistency, and imprecision. We were unable to conduct any of the predefined subgroup analyses.

Pyroptosis is a pattern of programmed cell death that significantly differs from apoptosis and autophagy in terms of cell morphology and function. The process of pyroptosis is characterized predominantly by the formation of gasdermin protein family-mediated membrane perforation, cell collapse, and the release of inflammatory factors, including IL-1β and IL-18. In recent years, with the rise of pyroptosis research, scholars have devoted time to study the mechanism of pyroptosis in kidney-related diseases. Pyroptosis is probably involved in kidney diseases through two pathways: the caspase-1-mediated canonical pathway and the caspase-4/5/11-mediated noncanonical pathway. In addition, some scholars have identified targets for the treatment of kidney-related diseases from the viewpoint of pyroptosis and developed corresponding medicines, which may become a recommendation for prognosis, targeted treatment, and clinical diagnosis of kidney diseases. This paper focuses on the up-to-date advances in the field of pyroptosis, especially on the key pathogenic role of pyroptosis in the development and progression of kidney diseases. It presents a more in-depth understanding of the pathogenesis of kidney diseases and introduces novel therapeutic targets for the prevention and clinical treatment of kidney diseases.

Objective. To perform a systematic evaluation of the efficacy and safety of combined treatment of Shenmai injection and chemotherapy for lung cancer. Methods. A literature search for randomized controlled trials (RCTs) describing the treatment of lung cancer by Shenmai injection and chemotherapy or chemotherapy alone was performed using the PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Value In Paper (VIP), China BioMed, and Wanfang databases. The databases were searched for entries published before September 1, 2019. Results. Thirty-seven RCTs, comprising a total of 2808 cases, were included in the present meta-analysis. Of these, 1428 cases were treated by Shenmai injection plus chemotherapy, and 1380 cases were treated only by chemotherapy. The results of meta-analysis showed that the combined treatment (Shenmai injection plus chemotherapy) increased the short-term efficacy of treatment (relative risk [RR] = 1.183, 95% confidence interval [CI] = 1.043–1.343, P < 0.01 ) and improved patients’ quality of life (RR = 1.514, 95%CI = 1.211–1.891, P < 0.01 ) compared with chemotherapy alone. With regard to the adverse effects, the combined treatment markedly reduced the incidence of white blood cell (WBC) reduction (RR = 0.846, 95%CI = 0.760–0.941, P < 0.01 ), platelet reduction (RR = 0.462, 95% CI = 0.330–0.649, P < 0.01 ), and hemoglobin reduction (RR = 0.462, 95% CI = 0.330–0.649, P < 0.01 ) and alleviated drug-induced liver injury (RR = 0.677, 95%CI = 0.463–0.990, P < 0.05 ). However, it did not offer a significant protective effect (RR = 0.725, 95%CI = 0.358–1.468, P < 0.05 ). The effect of the combined treatment on the occurrence of vomiting was considerable (RR = 0.889, 95%CI = 0.794–0.996, P < 0.05 ), and the combined treatment markedly increased the immunity of patients with lung cancer. Conclusion. The combined treatment of Shenmai injection plus chemotherapy enhanced the short-term efficacy of chemotherapy, improved the patient quality of life, alleviated the adverse effects of chemotherapeutics, and increased the patient immunity. These results should be confirmed by large-scale, high-quality RCTs.

BACKGROUND High-flow nasal oxygenation (HFNO) for pre-oxygenation in rapid sequence induction (RSI) has only been assessed in volunteer parturients without intubation. OBJECTIVES To evaluate the efficacy of HFNO in comparison with the conventional facemask for oxygenation during RSI for caesarean section under general anaesthesia. SETTING Operating room in a tertiary hospital. DESIGN Prospective randomised, controlled study. PARTICIPANTS Thirty-four healthy parturients undergoing general anaesthesia for caesarean section. INTERVENTIONS Parturients were randomly assigned to HFNO or standard facemask (SFM) group. MAIN OUTCOME MEASURES The primary outcome measure was the PaO2 immediately after intubation. Secondary outcomes included lowest saturation throughout the intubation procedure, end-tidal oxygen concentration (EtO2) on commencing ventilation, blood gas analysis (pH, PaCO2), fetal outcomes and intubation-related adverse events. RESULTS PaO2 in the HFNO group was significantly higher than that in SFM group (441.41 ± 46.73 mmHg versus 328.71 ± 72.80 mmHg, P

Objective. To develop and validate a risk assessment model for the prediction of the acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) in patients with idiopathic pulmonary fibrosis (IPF). Methods. We enrolled a total of 110 patients with IPF, hospitalized or treated as outpatients at Xuzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from July 2012 to July 2020. Of these, 78 and 32 patients were randomly assigned to training and test groups, respectively. The risk factors for AE-IPF were analyzed using logistic regression analysis, and a nomographic model was constructed. The accuracy, degree of calibration, and clinical usefulness of the model were assessed with the consistency index (C-index), calibration diagram, and decision curve analysis (DCA). Finally, the stability of the model was tested using internal validation. Results. The results of logistic regression analysis showed that a history of occupational exposure, diabetes mellitus (DM), essential hypertension (EH), and diffusion capacity for carbon monoxide (DLCO)% predicted were independent risk factors for AE-IPF prediction. The nomographic model was constructed based on these independent risk factors, and the C-index was 0.80. The C-index for the internal validation was 0.75, suggesting that the model had good accuracy. The decision curve indicated that for a threshold value of 0.04–0.66, greater clinical benefit was obtained with the AE-IPF risk prediction model. Conclusion. A customized AE-IPF prediction model based on a history of occupational exposure, DM, EH, and DLCO% predicted provided a reference for the clinical prediction of AE-IPF.

BackgroundThe evolving pandemic of COVID-19 is arousing alarm to public health. According to epidemiological and observational studies, coagulopathy was frequently seen in severe COVID-19 patients, yet the causality from specific coagulation factors to COVID-19 severity and the underlying mechanism remain elusive.MethodsFirst, we leveraged Mendelian randomization (MR) analyses to assess causal relationship between 12 coagulation factors and severe COVID-19 illness based on two genome-wide association study (GWAS) results of COVID-19 severity. Second, we curated clinical evidence supporting causal associations between COVID-19 severity and particular coagulation factors which showed significant results in MR analyses. Third, we validated our results in an independent cohort from UK Biobank (UKBB) using polygenic risk score (PRS) analysis and logistic regression model. For all MR analyses, GWAS summary-level data were used to ascertain genetic effects on exposures against disease risk.ResultsWe revealed that genetic predisposition to the antigen levels of von Willebrand factor (VWF) and the activity levels of its cleaving protease ADAMTS13 were causally associated with COVID-19 severity, wherein elevated VWF antigen level (P = 0.005, odds ratio (OR) = 1.35, 95% confidence interval (CI): 1.09-1.68 in the Severe COVID-19 GWAS Group cohort; P = 0.039, OR = 1.21, 95% CI: 1.01-1.46 in the COVID-19 Host Genetics Initiative cohort) and lowered ADAMTS13 activity (P = 0.025, OR = 0.69, 95% CI: 0.50-0.96 in the Severe COVID-19 GWAS Group cohort) lead to increased risk of severe COVID-19 illness. No significant causal association of tPA, PAI-1, D-dimer, FVII, PT, FVIII, FXI, aPTT, FX or ETP with COVID-19 severity was observed. In addition, as an independent factor, VWF PRS explains a 31% higher risk of severe COVID-19 illness in the UKBB cohort (P = 0.047, OR per SD increase = 1.31, 95% CI: 1.00-1.71). In combination with age, sex, BMI and several pre-existing disease statues, our model can predict severity risks with an AUC of 0.70.ConclusionTogether with the supporting evidence of recent retrospective cohort studies and independent validation based on UKBB data, our results suggest that the associations between coagulation factors VWF/ADAMTS13 and COVID-19 severity are essentially causal, which illuminates one of possible mechanisms underlying COVID-19 severity. This study also highlights the importance of dynamically monitoring the plasma levels of VWF/ADAMTS13 after SARS-CoV-2 infection, and facilitates the development of treatment strategy for controlling COVID-19 severity and associated thrombotic complication.