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As the key component for the Higgs operating mode of Circular Electron–Positron Collider (CEPC), the electrostatic–magnetic deflectors are required by the double ring collider to separate the electron and the positron beams horizontally in the RF regions. The electric field is required to reach 2 MV/m with the vacuum pressure of less than 2 × 10−10 Torr. The deflectors make use of both electric and magnetic fields to deflect the beams. The incoming beam gets zero deflection, but the outgoing beam is deflected by the combined effect of the electric and magnetic forces. W and Z modes use the same cavities with H mode to save budget. The deflectors are large contributors to the overall beam impedance which is necessary to be reduced as much as possible. The electric and magnetic field optimization has been performed by the Opera. The beam impedance study has been carried out using the Computer Simulation Technology (CST) particle studio. The shape of the electrode is optimized for a good electric field homogeneity (± 0.05%) in 46 mm × 40 mm region. The electric field and the magnetic field could be matched perfectly in the main body of the deflector by bending the electrodes and introducing magnetic field clamps and mirror plates. The beam loss factor decreases by about 20% via the introduction of ground electrodes and tapering ends. The design results successfully meet the physical requirements, and the mechanical design has been finished.

Background Movable collimators for the circular electron positron collider (CEPC) are required to cut off spent electrons/positrons just near the beam orbit and reduce the background of the detector. Due to the extremely high energy and luminosity of CEPC, a lot of challenges are brought to the collimators, including the huge synchrotron radiation power, the high-energy beam impact, and low impedance requirement. Purpose The purpose of this paper is to design a movable collimator suitable for CEPC and calculate its performance. Method Based on geant4 simulations and finite element method (FEM) analyses, a lot of studies were done: synchrotron radiation power, thermal and mechanical calculation, beam impact, and impedance, respectively. Result The maximum temperature of the design during normal operation is 143 $$^{\circ }$$ C, and the loss factor is only 0.021 V/pC ignoring the shielding of clearance. Conclusions The conceptual design of collimator was completed, and the calculations show the design can work well under normal operating condition.

Background Only few pathogens that cause lower respiratory tract infections (LRTIs) can be identified due to limitations of traditional microbiological methods and the complexity of the oropharyngeal normal flora. Metagenomic next-generation sequencing (mNGS) has the potential to solve this problem. Methods This prospective observational study sequentially enrolled 93 patients with LRTI and 69 patients without LRTI who visited Peking University People’s Hospital in 2019. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS (DNA and RNA) and traditional microbiological assays. Human transcriptomes were compared between LRTI and non-LRTI, bacterial and viral LRTI, and tuberculosis and nontuberculosis groups. Results Among 93 patients with LRTI, 20%, 35%, and 65% of cases were detected as definite or probable pathogens by culture, all microbiological tests, and mNGS, respectively. Our in-house BALF mNGS platform had an approximately 2-working-day turnaround time and detected more viruses and fungi than the other methods. Taking the composite reference standard as a gold standard, it had a sensitivity of 66.7%, specificity of 75.4%, positive-predictive value of 78.5%, and negative-predictive value of 62.7%. LRTI-, viral LRTI–, and tuberculosis-related differentially expressed genes were respectively related to immunity responses to infection, viral transcription and response to interferon-γ pathways, and perforin 1 and T-cell receptor B variable 9. Conclusions Metagenomic DNA and RNA-seq can identify a wide range of LRTI pathogens, with improved sensitivity for viruses and fungi. Our in-host platform is likely feasible in the clinic. Host transcriptome data are expected to be useful for the diagnosis of LRTIs.

Systemic rheumatic diseases are a heterogeneous group of disorders characterized by profound immune dysregulation. Recent discoveries have led to a significant resurgence of interest in neutrophils as shapers of immune dysregulation and as triggers of organ damage in rheumatic diseases. Neutrophils contribute to the initiation, promotion, and perpetuation of immune dysregulation through a variety of mechanisms including synthesis of proinflammatory cytokines, direct tissue damage through degranulation and synthesis of reactive oxygen species, and the formation of neutrophil extracellular traps (NETs). The identification of a subset of proinflammatory neutrophils, the low-density granulocytes (LDGs), which promote Th1 responses and cause endothelial dysfunction, has further strengthened the pathogenic role of neutrophils in various rheumatic diseases. The presence of autoantibodies targeting molecules commonly expressed in neutrophils suggests that neutrophils, particularly NETs, may be a source of autoantigens. An imbalance between NET formation and degradation, which leads to increased NET levels in the circulation and tissues, could enhance the exposure of the immune system to modified autoantigens, promote vascular disease, and increase tissue damage. This review will present an overview of recent advances in our understanding of how neutrophil dysregulation modulates the innate and adaptive immune responses in systemic rheumatic diseases and their putative contributions to pathogenicity. Understanding the potential pathogenic role of neutrophil dysregulation may provide better molecular candidates for therapeutic targeting, and ultimately promote improvements in the clinical outcomes in rheumatic diseases.

Our study was aimed to identify potential lncRNAs related to laryngeal cancer (LC) and explore their potential regulatory mechanisms. RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to identify differentially expressed genes (DEGs). Receiver operating characteristic (ROC) curve analysis was performed to analyze the sensitivity and specificity of differentially expressed lncRNAs (DElncRNAs) as biomarkers. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expressed DElncRNAs and differentially expressed mRNAs (DEmRNAs) associated with clinical indicators. We performed functional enrichment analysis on target genes and constructed a lncRNA–miRNA–mRNA ceRNA network. The expression of lncRNA and mRNAs in ceRNA network were validated via RT-qPCR. By differential expression analyzing TCGA and GEO data, 6 up-regulated DElncRNAs were consistently identified, and their predictive performance were suggested to be considerable via ROC curve. 1998 DEmRNAs and 6 lncRNAs were involved in the construction of WGCNA network, in which the MEblue module was positively correlated with clinical stage. Functional enrichment analysis of this module suggested that the functions of DEmRNAs were closely involved in PI3K/Akt pathway. A ceRNA network composed of MSC-AS1, miR-429, COL4A1 and ITGAV was constructed. It was verified by RT-qPCR that the lncRNA and mRNAs in the ceRNA network were highly expressed in multiple LC tissues. This study identified lncRNA MSC-AS1 as a potential biomarker of LC. Besides, we constructed a ceRNA network, which provides a basis for the research of ceRNA in LC.

ObjectiveNeutrophilia is a hallmark of adult-onset Still disease (AOSD). We aimed to investigate the levels of granulocyte colony-stimulating factor (G-CSF), an essential regulator of neutrophil production and function, in the pathogenesis of AOSD.MethodsSera were collected from 70 patients with AOSD and 20 healthy controls (HCs). The levels of G-CSF were determined by ELISA. Low-density granulocytes (LDGs) were quantified by flow cytometry. Correlations between G-CSF levels and disease activity, laboratory variables, and LDG levels in patients with AOSD were analyzed by Spearman correlation test.ResultsPatients with active AOSD presented significantly higher levels of G-CSF compared to inactive AOSD patients (P < 0.001) and HCs (P < 0.0001). The G-CSF levels were significantly decreased after active AOSD patients achieved disease remission (P = 0.0015). The G-CSF levels were significantly correlated with C-reactive protein, erythrocyte sedimentation rate, ferritin, and systemic score in AOSD (P < 0.0001). Significant correlations between the levels of G-CSF and circulating neutrophils (P < 0.0001), neutrophil-to-lymphocyte ratio (P < 0.0001), percentages of LDGs in the peripheral blood mononuclear cells (P = 0.004), as well as absolute numbers of circulating LDGs (P = 0.018) were identified. Patients with fever, evanescent rash, sore throat, arthralgia, myalgia, lymphadenopathy, or hepatomegaly/elevated liver enzymes displayed significantly higher levels of G-CSF compared to patients without these manifestations (P < 0.05).ConclusionOur findings indicate that G-CSF is implicated in the pathogenesis of AOSD, and targeting G-CSF may have therapeutic potential for AOSD. In addition, introducing circulating G-CSF levels into the clinical assessment system may help to monitor disease activity.

Objectives Neutrophilia is a hallmark of adult-onset Still’s disease (AOSD). This study aimed to investigate the role of a distinct subset of granulocytes, the low-density granulocytes (LDGs) in the pathogenesis of AOSD. Methods A total of 56 patients with AOSD were included in the study. LDGs were quantified by flow cytometry. Correlations between LDGs with disease activity and laboratory parameters were determined by Spearman’s nonparametric test. The cellular sources of the pro-inflammatory cytokines in AOSD were determined by intracellular staining. Results Active AOSD patients displayed significantly higher levels of LDGs compared with inactive AOSD patients and healthy controls (HCs) (P Conclusion Active AOSD is associated with elevated levels of a pro-inflammatory subset of neutrophils, the LDGs that produce IL-6. Our data highlight an unappreciated role of LDGs in the aberrant innate immune responses in AOSD.

Objectives Influenza vaccination is effective in preventing infections in most people. This study aimed to assess the changes of immune responses in primary Sjögren’s Syndrome (pSS) patients after influenza vaccination and determine the safety of influenza vaccination. Methods A total of 17 patients with pSS and 16 healthy controls (HCs) were included. Peripheral mononuclear cells were analysed by flow cytometry. Vaccine-specific antibodies were determined by ELISA. Clinical features and serological responses were monitored. Results The percentages of T follicular helper cell (Tfh) were significantly elevated in HCs after vaccination (P=0.0005), while no significant differences in the levels of Tfh in pSS patients were identified (P=0.1748). The proportions of Th2 cells were significantly decreased after vaccination in both pSS patients and HCs (P0.05), although a trend towards higher levels of Th1 cells was observed (P=0.0830). No significant changes in the proportions of memory B cells and plasmablasts were observed after vaccination. Patients with pSS developed higher levels of vaccine-specific IgGs compared with HCs (P=0.001). No significant changes in disease manifestations and laboratory parameters were observed after vaccination. No increased vaccination related adverse effect was observed in pSS. Conclusion Our findings suggest the feasibility of applying influenza vaccines to patients with pSS, raising awareness for vaccination among the rheumatology community and involved healthcare professionals.

Introduction. Increasing evidence demonstrates unfavourable outcomes in bloodstream infections (BSI) due to the carbapenem-resistant Acinetobacter baumannii complex (CRAB). Aim. To investigate the differences in risk factors, clinical characteristics and outcomes in patients with A. baumannii complex BSI stratified by carbapenem resistance, a prospective multi-center study was conducted. Methodology. Information was collected in a predefined form. A total of 317 cases was included for comparison between CRAB BSI vs. carbapenem-susceptible A. baumannii complex (CSAB) BSI. Among these cases, 229 cases were defined as CRAB BSI and 88 cases as CSAB BSI. Results. Univariable analysis showed that male gender, underlying neurologic disease, prior carbapenems exposure, intensive care unit (ICU) stay, presence of central venous catheter, endotracheal intubation, tracheotomy, Foley catheter, nasogastric intubation, lower respiratory tract infections and catheter-related infections were more prevalent in CRAB BSI. Only male gender, prior carbapenems exposure and presence of endotracheal intubation persisted as independent risk factors for acquiring CRAB BSI. Patients with CRAB BSI displayed unfavourable outcomes characterized by failure of pathogen clearance, continuous fever, disease aggravation and higher incidence of 30-day all-cause mortality. Multivariate analysis demonstrated carbapenem resistance as an independent risk factor for 30-day all-cause mortality. Conclusion. Our findings reveal the epidemiological differences between CRAB BSI and CSAB BSI in a Chinese cohort. Our data suggest that carbapenem resistance has a significant impact on mortality for patients with A. baumannii complex BSI, further strengthening the importance of active prevention and control strategies for the spread of CRAB in Chinese hospitals.

I read with great interest the article by Trahtemberg et al 1 on the clinical relevance of antiphospholipid antibodies (aPLs), in particular anticardiolipin antibodies (aCLs), in critically ill COVID-19 positive and negative patients. Severe COVID-19 is associated with a hypercoagulable state. Early studies identified the presence of aPLs in critically ill COVID-19 patients,2 which has attracted considerable attention as the presence of aPLs is one of the mechanisms leading to coagulopathy. Substantial efforts then tried to associate the thrombotic events seen in COVID-19 to aPLs status. The results seem negative, but a number of different types of autoantibodies were identified.3 Chang et al recently reported that autoantibodies were present in approximately half of the hospitalised patients with COVID-19 but in less than 15% of healthy controls.4 In addition to aCLs and anti-beta 2 glycoprotein 1 antibodies (aβ2-GP1), they also identified autoantibodies targeting autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes as well as targeting interferons/interleukins and other cytokines.4 These findings suggest that COVID-19, in particular patients with severe/critical …

As a traditional Chinese medicine-originated disease-modifying anti-rheumatic drug prescription, Baihu-Guizhi decoction (BHGZD) is extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic efficacy. Mechanically, our previous data indicated that BHGZD may ameliorate RA partially by restoring the balance of the “inflammation-immune” system through regulating theTLR4-c-Fos-IL2-TNF-alphaaxis. Toll-like receptor 4 (TLR4) has been revealed to be involved in the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex. Thus, the aim of the current study was to determine the regulatory effects of BHGZD on the TLR4–mediated inflammasome activation during RA progression based on the modified adjuvant-induced arthritis model (AIA-M) and the lipopolysaccharide/adenosine triphosphate (LPS/ATP)–induced pyroptosis cellular models. As a result, oral administration of BHGZD exhibited prominent improvement in the disease severity of AIA-M rats, such as reducing the redness and swelling of joints, arthritis incidence, arthritic scores, and diameter of the limb and increasing pain thresholds. In line with thein vivofindings, BHGZD treatment effectively inhibited the LPS/ATP–induced pyroptosis of both Raw264.7 macrophage and MH7A cellsin vitroby reducing pyroptotic cell death morphology (swollen cells) and decreasing propidium iodide–positive and terminal deoxynucleotidyl transferase–mediated dUTP-fluorescein nick end labeling (TUNEL)–positive cells. Notably, the increased expression levels of TLR4, NLRP3, interleukin 1β, and interleukin 18 proteins and the elevated activities of caspase-1 and lactic dehydrogenase inin vivoandin vitrodisease models were markedly reversed by the treatment with BHGZD. In conclusion, the above findings proved the immunomodulatory and anti-inflammatory activities of BHGZD, especially in pyroptosis, which may be attributed to the activation of TLR4–mediated NLRP3 inflammasome signaling.

Objective: Human epididymis protein 4 (HE4) have been implicated in the pulmonary involvements. We aimed to investigate the clinical utility of HE4 in clinical stratification in patients with rheumatoid arthritis (RA).Methods: This study included a discovery cohort comprising 70 RA patients and 64 healthy controls (HCs), and a validation cohort comprising 98 RA patients and 75 HCs. Human epididymis protein 4 were determined by electrochemical luminescence analyzer.Results: The levels of HE4 were significantly elevated in patients with RA compared to HCs. The positive rates of HE4 in patients with RA and HCs were 50.0% and 0, respectively, in the discovery cohort and 53.1 and 1.3%, respectively, in the validation cohort. When RA patients were subgrouped according to HE4 status, HE4-positive group displayed higher prevalence of interstitial lung disease (ILD) compared to HE4-negative group (28.6 vs. 11.4% in discovery cohort and 57.7 vs. 8.7% in the validation cohort). A positive correlation between the levels of HE4 with the degree of lung impairment was identified. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.3 pmol/L in HE4 for distinguishing RA-ILD from RA-non ILD with the areas under the curve (AUC) of 0.790. Multivariate logistic regression analysis illustrated that high levels of HE4 independently identified patients with RA-ILD (OR, 9.080, p < 0.001).Conclusion: Our findings showed a novel role of HE4 in RA risk stratification, suggest that introducing HE4 to the current RA test panel may serve as an indicator in identifying RA patients for further RA-ILD workups, such as high-resolution computed tomography (HRCT).

Even with the rapid advances in medical sciences, histopathological diagnosis is still considered the gold standard in diagnosing cancer. However, the complexity of histopathological images and the dramatic increase in workload make this task time consuming, and the results may be subject to pathologist subjectivity. Therefore, the development of automatic and precise histopathological image analysis methods is essential for the field. In this paper, we propose a new hybrid convolutional and recurrent deep neural network for breast cancer histopathological image classification. Based on the richer multilevel feature representation of the histopathological image patches, our method integrates the advantages of convolutional and recurrent neural networks, and the short-term and long-term spatial correlations between patches are preserved. The experimental results show that our method outperforms the state-of-the-art method with an obtained average accuracy of 91.3% for the 4-class classification task. We also release a dataset with 3771 breast cancer histopathological images to the scientific community that is now publicly available at http://ear.ict.ac.cn/?page_id=1616 . Our dataset is not only the largest publicly released dataset for breast cancer histopathological image classification, but it covers as many different subclasses spanning different age groups as possible, thus providing enough data diversity to alleviate the problem of relatively low classification accuracy of benign images.

Accurate and reliable measurements of the 3D flame temperature profile are highly desirable to achieve in-depth understanding of the combustion and pollutant formation processes. In this paper, a measurement method for reconstruction of a 3D flame temperature profile was proposed by using a light field camera. It combines the convolution imaging model and radiative transfer equation and takes into account the characteristics of emission, absorption, and scattering of a semitransparent flame. According to the point spread function characteristics of the imaging system, the number and positions of the refocus planes were set by comprehensive consideration of the reconstruction accuracy and efficiency. The feasibility of the present method was proved by numerical simulation and an experiment of a candle flame. This method achieves the reconstruction of a 3D asymmetric flame profile through a single exposure of a single camera, which overcomes the problem of complexity of a multicamera system and the time delay of a conventional scanning camera system.

BackgroundWe aimed to investigate the clinical utility of human epididymis protein 4, a tumor biomarker being widely utilized in clinical practice in the diagnosis of ovarian cancer, in primary Sjögren’s Syndrome (pSS).MethodsA total of 109 pSS patients and 113 healthy controls (HCs) were included in the study. HE4 were determined by Roche Cobas E601 electrochemical luminescence analyzer. Clinical and laboratory findings were reviewed, and the relationships between HE4 and clinical parameters were determined by Spearman’s correlation test. The European league against rheumatism Sjögren’s syndrome disease activity index (ESSDAI) was utilized to evaluate disease activity.FindingsThe levels of HE4 were significantly elevated in patients with pSS compared to HCs (103.65 pmol/L vs. 46.52 pmol/L, pr=0.462, pr=0.442, pr=0.320, p=0.001) were observed. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.90 pmol/L and 128.05 pmol/L for distinguishing patients with pulmonary and renal involvements, with the areas under the ROC curve (AUCs) of 0.778 (95%CI 0.685-0.870, pp=0.001), respectively. Among patients with pulmonary involvement, the levels of HE4 were positively correlated with the semiquantitative HRCT grade (r=0.417, p=0.016), and negatively correlated with the percentage of forced vital capacity (FVC) (r= -0.460, p=0.047) and diffusing capacity of the lung for carbon monoxide (DLco) (r= -0.623, p=0.004). For patients with renal involvement, HE4 was positively correlated with creatinine (r=0.588, p=0.021) and negatively correlated with estimated glomerular filtration rate (r= -0.599, p=0.030).ConclusionsOur findings demonstrated a novel role of HE4 in clinical stratification of pSS, suggesting that introducing HE4 to the current pSS test panel may provide additional diagnostic value, particularly in evaluating disease activity and pulmonary/renal involvements.

The recent identifications of a subset of proinflammatory neutrophils, low-density granulocytes, and their ability to readily form neutrophil extracellular traps led to a resurgence of interest in neutrophil dysregulation in the pathogenesis of systemic lupus erythematosus (SLE). This article presents an overview on how neutrophil dysregulation modulates the innate and adaptive immune responses in SLE and their putative roles in disease pathogenesis. The therapeutic potential of targeting this pathogenic process in the treatment of SLE is also discussed.

Natural pigments, including carotenoids, flavonoids and anthocyanidins, determine the attractive color of fruits. These natural pigments are essential secondary metabolites, which play multiple roles in the whole life cycle of plants and are characterized by powerful antioxidant activity. After decades of research and development, multiple benefits of these natural pigments to human health have been explored and recognized and have shown bright application prospects in food, medicine, cosmetics and other industries. In this paper, the research progress of natural fruit pigments in recent years was reviewed, including the structural characteristics and classification, distribution in fruits and analysis methods, biosynthetic process, antioxidant capacity and mechanism, bioaccessibility and bioavailability, and health benefits. Overall, this paper summarizes the recent advances in antioxidant activity and other biological functions of natural fruit pigments, which aims to provide guidance for future research.

The light field sectioning pyrometry (LFSP) has proven a significant advancement for in-situ measurement of flame temperature through a single light field camera. However, the spatial resolution of LFSP is limited, which severely inhibits the measurement accuracy. This paper aims to evaluate the spatial resolution of LFSP for flame temperature measurement quantitatively. A theoretical model of the spatial resolution is established based on optical parameters and point spread function of the light field camera. The spatial resolution is then numerically analyzed with different parameters of light field cameras. Based on the theoretical model, a novel cage-typed light field camera with a higher spatial resolution of LFSP is developed and experimentally evaluated. A significant improvement of spatial resolution about 17% and 50% in lateral and depth directions, respectively, is achieved. Results show that the spatial resolution is in good agreement with the theoretical model. The LFSP is then evaluated under different combustion cases and their temperatures are reconstructed.

Background: Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to halt the spread of coronavirus disease 2019 (COVID-19) pandemic. As a promising inactivated SARS-CoV-2 vaccine, CoronaVac (developed by Sinovac Life Sciences, Beijing, China) is currently undergoing its clinical trials in several countries and showing good results. We investigated the immune mechanisms underlying CoronaVac from the perspective of single-cell gene expressions and immune function features. Methods: In this controlled study, 13 healthy participants aged 21–54 years were recruited in the vaccination group and intramuscularly injected with two doses of CoronaVac (3 μg / 0·5 mL per dose, at Day00 and Day28, right after blood sampling), with peripheral blood samples collected at Day00, Day14, Day28, Day35, and Day45 to monitor dynamic changes. As positive control, 12 participants aged 28–75 years that had recovered from COVID-19 for approximately eight months were recruited in the recovery group with peripheral blood samples collected. Considering the high cost of sequencing, 11 samples from two healthy participants (H1 and H2) with four timepoints (Day00, Day14, Day28, and Day35) and three recovered participants (R1, R2, and R3) with one timepoint (Month8) were randomly chosen for single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC). The transcriptomics of PBMC and its constituent cells were analyzed as gene expression responses. For samples from all 25 participants, the serum neutralizing antibody titer to live SARS-CoV-2 and the in vitro cytokine release activity of CD4+T cells were assayed as immune function responses. Findings: Single-cell RNA sequencing showed that the PBMC transcriptomics after vaccination resembled the COVID-19 recovery control more than that before vaccination, which also applied to its constituent cells such as B cells, T cells, NK cells, and myeloid cells. Gradual transitions of PBMC transcriptomics were observed from Day14 to Day28 and Day35 in vaccination groups, which finally approached the recovery control. The B cell levels in PBMC increased after each vaccination, while the T cell levels mainly increased within four weeks after the first vaccination and peaked at Day28. The serum neutralizing antibody titer to live SARS-CoV-2 was low within four weeks after the first vaccination, but the second vaccination could induce significantly higher serum neutralizing antibody titers due to the immune memory. For both vaccinated participants and recovered participants, the upregulated JUN/FOS network and tuned expressions of immunoglobulin fragments such as IGHV3-30 and IGLV2-23 were observed in B cells. By purifying CD4+T cells from PBMC and re-stimulating them with CoronaVac in vitro, five cytokines were significantly released, including Th1 cytokines (IFN-γ and IL-2) and Th2 cytokines (IL-4, IL-6, and IL-10). Th1 cytokines were mainly activated at Day14, Day28, and Day35, supporting cellular immune responses at early stages when the serum neutralizing antibody titer was low. Th2 cytokines were mainly activated at Day28, Day35, and Day45, supporting humoral immune responses at later stages, especially after the second vaccination. Interpretation: Two vaccinations of CoronaVac (3 µg per dose, with an interval of 28 days) could make positive gene expression and immune responses in healthy participants, as revealed by single-cell PBMC transcriptomics and immune function assays. Funding Statement: China’s National Science and Technology Major Projects for Major New Drugs Innovation and Development. Declaration of Interests: QG, YH, XM, and SZ are employees of Sinovac Life Sciences, Beijing, China. The other authors declare no competing interests. Ethics Approval Statement: This study was approved by the Peking University Biomedical Ethics Committee.

Traumatic spinal cord injury (SCI) is a devastating disease of the central nervous system with long-term disability and high mortality worldwide. Revascularization following SCI provides nutritional supports to rebuild and maintain the homeostasis of neuronal networks, and the subsequent promotion of angiogenesis is beneficial for functional recovery. Oxidative stress drastically produced following SCI has been contributed to endothelial dysfunction and the limited endogenous repair of microvasculature. Recently, exosomes, being regarded as potential therapeutic candidates for many kinds of diseases, have attracted great attentions due to its high bioavailability, safety, and stability. Microglia have been reported to exhibit proangiogenic function and guide the forming of vasculature during tissue repair. However, the specific role of microglia-derived exosomes (MG-Exos) played in SCI is still largely unknown. In the present study, we aimed to evaluate whether MG-Exos could protect spinal cord microvascular endothelial cells (SCMECs) against the toxic effects of oxidative stress, thus promote SCMECs’ survival and function. We also investigated the protective effects of MG-Exos in the mouse model of SCI to verify their capability. Our results demonstrated that MG-Exo treatment significantly decreased the level of oxidative stress (ROS), as well as did the protein levels of NOX2 when bEnd.3 cells were exposed to H2O2-induced oxidative stress in vitro and in vivo. Functional assays showed that MG-Exos could improve the survival and the ability of tube formation and migration in H2O2-induced bEnd.3 in vitro. Moreover, MG-Exos exhibited the positive effects on vascular regeneration and cell proliferation, as well as functional recovery, in the mouse model of SCI. Mechanically, the keap1/Nrf2/HO-1 signaling pathway was also investigated in order to unveil its molecular mechanism, and the results showed that MG-Exos could increase the protein levels of Nrf2 and HO-1 via inhibiting the keap1; they also triggered the expression of its downstream antioxidative-related genes, such as NQo1, Gclc, Cat, and Gsx1. Our findings indicated that MG-Exos exerted an antioxidant effect and positively modulated vascular regeneration and neurological functional recovery post-SCI by activating keap1/Nrf2/HO-1 signaling.

We read with great interest the article by Le Joncour et al 1 on how neutrophil extracellular traps (NETs) contribute to the vascular manifestations in patients with Behcet’s disease (BD). In their well-designed study, the authors found that neutrophils from BD patients were more prone to form NETs, which contributes to the elevated levels of circulating NETs.1 The authors further identified that NETs were detected around affected blood vessels and NETs levels were significantly higher in patients with BD with vascular involvement, suggesting that these structures are implicated in the vascular manifestations in this disease.1 NETs are extracellular web-like structures composed of nuclear components bound to neutrophil-derived proteins.2 NETs have been shown to induce vascular damage and are implicated in thrombosis.3 An important source of NETs is a subset of proinflammatory neutrophils, the low-density granulocytes (LDGs). LDGs are found in the peripheral blood mononuclear cell (PBMCs) fraction following density-gradient separation of whole blood.4 The levels of LDGs are increased in a number of autoimmune and autoinflammatory disorders, such as systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody-associated vasculitis, and adult-onset Still’s disease.4–6 The pathogenic role of LDGs in these diseases is partially due to their significantly enhanced ability to form NETs.4 7 As elevated levels of NETs are increased in BD,1 8 we evaluated the levels of LDGs in patients …

This paper presents a deep learning based user authentication system which aims to identify an individual using data gathered from a mouse and the user's eyes during computer use in a controlled environment. A stacked bidirectional and unidirectional Long Short-Term Memory Recurrent Neural Network (SBV-LSTM-RNN) is introduced to distinguish a legitimate user from impostors. As one of the few attempts of using fusion of mouse and eye movement for user authentication, the proposed system, when adopted on a small dataset, has shown promising improvement compared to a similar system where fusion of eye and mouse modalities and a traditional machine learning method are used.

This chapter focuses on how cutting-edge artificial intelligence (AI) technology that is centered around machine learning can help advance data analytics. It discusses the applications of a subfield of AI, natural language processing (NLP), in the domain of text analytics. Predictive analytics utilizes statistical modeling and machine learning techniques to make predictions about future outcomes based on the patterns found in the existing data. The development of advanced analytics has greatly benefited from the advancement of applications of machine learning algorithms which is an intersection of statistics and computer science. The applications of NLP today are incredibly diverse. It spreads in various fields such as machine translation, question answering, information extraction, natural language generation, writing assistance, video scripting, text categorization, sentiment analysis (SA), speech technologies, hate speech detection and fake news detection. SA focuses on the extraction of people’s sentiments, opinions, emotions, and attitudes toward entities such as services, products, organizations, individuals, issues, events, topics, and their attributes.

In view of the shortcomings of the existing tunnel communication technology, based on the principle of wireless sensor network (WSN), the important research achievements in the field of tunnel wireless communication in recent years are summarized in terms of topology structure, module design and tunnel application of Zigbee technology. On the basis of the above review, the future research direction of tunnel wireless communication technology is prospected, which provides reference for the development of tunnel wireless communication technology.

Thin film is a good choice for in-plane strain sensing and is also technical compatible with modern electronic industry. In this paper, a thin film based piezotronic transistors array was demonstrated for the first time. The piezotronic effect of the sensing units was investigated and qualitative characterized. The strain sensitivity (gauge factor) of the units was derived up to 199, which is around 100 times of the sensitivity of the commercial foil gauge. After calibration on every sensing unit, the distribution of the strain applied on the device was successfully measured and mapped by the sensor array, which show the big potential of the thin film based piezotronic transistors array on the application of high space resolution, high sensitivity field deformation sensing.

Unlike in other autoimmune liver diseases such as autoimmune hepatitis and primary biliary cholangitis, the role and nature of autoantigenic targets in primary sclerosing cholangitis (PSC), a progressive, chronic, immune-mediated, life threatening, genetically predisposed, cholestatic liver illness, is poorly elucidated. Although anti-neutrophil cytoplasmic antibodies (ANCA) have been associated with the occurrence of PSC, their corresponding targets have not yet been identified entirely. Genome-wide association studies revealed a significant number of immune-related and even disease-modifying susceptibility loci for PSC. However, these loci did not allow discerning a clear autoimmune pattern nor do the therapy options and the male gender preponderance in PSC support a pathogenic role of autoimmune responses. Nevertheless, PSC is characterized by the co-occurrence of inflammatory bowel diseases (IBD) demonstrating autoimmune responses. The identification of novel autoantigenic targets in IBD such as the major zymogen granule membrane glycoprotein 2 (GP2) or the appearance of proteinase 3 (PR3) autoantibodies (autoAbs) have refocused the interest on a putative association of loss of tolerance with the IBD phenotype and consequently with the PSC phenotype. Not surprisingly, the report of an association between GP2 IgA autoAbs and disease severity in patients with PSC gave a new impetus to autoAb research for autoimmune liver diseases. It might usher in a new era of serological research in this field. The mucosal loss of tolerance against the microbiota-sensing GP2 modulating innate and adaptive intestinal immunity and its putative role in the pathogenesis of PSC will be elaborated in this review. Furthermore, other potential PSC-related autoantigenic targets such as the neutrophil PR3 will be discussed. GP2 IgA may represent a group of new pathogenic antibodies, which share characteristics of both type 2 and 3 of antibody-mediated hypersensitive reactions according to Coombs and Gell.

This article discusses recent studies of piezotronics and piezo-phototronics of two-dimensional (2D) materials. Two-dimensional semiconductor materials have demonstrated excellent electronic and optoelectronic properties, and these ultrathin materials are candidates for next-generation devices. Among 2D semiconductors, transition-metal dichalcogenides in particular have large in-place piezoelectricity due to the noncentrosymmetry along the armchair direction. A strong coupling of piezoelectric and semiconducting properties has been reported for Schottky contacts and p–n junctions, even in single-layer materials. Since the carrier concentration of ultrathin 2D materials can be easily modulated by external piezocharges, layered composites of ferroelectric/2D materials also show promising piezotronic and piezo-phototronic properties.

The mechanisms leading to the development of premature atherosclerosis and vascular injury in systemic lupus erythematosus (SLE) remain to be fully elucidated. This is a comprehensive review of recent research developments related to the understanding of cardiovascular disease (CVD) in lupus.SLE patients with lupus nephritis display significantly increased risk of myocardial infarction and CVD mortality than SLE patients without lupus nephritis. SLE disease-related parameters could be taken into consideration when calculating CVD risks. The type I interferon pathway is detrimental to the vasculature and may contribute to the development of insulin resistance. The level of low-density granulocytes, a distinct subset of proinflammatory neutrophils present in SLE, was independently associated with coronary plaque burden and endothelial dysfunction. Invariant natural killer T cells may promote an atheroprotective effect in SLE patients with asymptomatic atherosclerotic plaques. Oxidized lupus high-density lipoprotein promotes proinflammatory responses in macrophages.Recent discoveries have further strengthened the critical role of SLE-related immune dysregulation and metabolic disturbances in promoting accelerated CVD. Understanding how these pathogenic factors promote vascular injury may provide better molecular candidates for therapeutic targeting, and ultimately to improve CVD outcomes.

With the continuous development of the internet of things (IoT) technology, large amount of data has been generated by lots of IoT devices which require large-scale data processing technologies and storage technologies. Cloud computation is a paradigm for handling such massive data. With the help of cloud computing, IoT devices can utilize the data more efficiently, conveniently and faster. Therefore, how to promote the better integration of the IoT and cloud computing is an interesting research problem. In the big data era, group sum evaluation over outsourced data stream collected by IoT devices is an essential building block in many stream applications, such as statistical monitoring, data mining, machine learning and so on. Thus it is very valuable to design a mechanism to verify the correctness of the group sum evaluation over the outsourced data streams, especially when the data streams are originated from multiple data sources. Recently, Liu et al. proposed such a scheme to solve this problem. However in this paper, we show their scheme is not secure. Concretely, the adversary can easily forge tags for outsourced data, thus the correctness of the group sum evaluation can not be guaranteed anymore. Furthermore, we give two improved schemes which can resist our attack and analyze their security. Finally, we roughly evaluate the performance of our two improved schemes. Our first scheme almost shares the same efficiency as Liu et al.’s proposal but with no security flaw, the second scheme shares the same structure with Liu et al.’s proposal and can be compatible with the existing composite order bilinear pairing cryptosystem.

Experimental measurements and numerical studies with CFD method were performed to investigate the deagglomeration performance including the deagglomeration mechanism and the smallest attainable size of nano-clusters in in-line HSM under different operating conditions and structural parameters. The results indicate that the deagglomeration is dominated by rupture mechanism under lower energy input while controlled by erosion mechanism at higher energy input. Besides, the smallest size of nano-clusters is 131 nm, regardless of operating conditions and structural parameters of rotor–stator head. The deagglomeration performance can be effectively improved through increasing rotor speed, employing self-cycle mode and appropriately reducing residence time. In addition, the deagglomeration performance is also significantly impacted by the structural parameters involving rotor tooth number, shear gap and rotor teeth inclination. An ANN model is established to correlate the Sauter mean diameter d32 with the investigated parameters, and the comparison between estimated data and experimental data suggests that this method achieved an accurate prediction of d32 for the whole dispersion.

We report the piezotronic effect on the performance of humidity detection based on a back-to-back Schottky contacted monolayer MoS2 device. By introducing an upswept mechanical strain, the in-plane electrical polarization can be induced at the MoS2/metal junction region. The polarization charges can modify the Schottky barrier height at the interface of MoS2/metal junction, subsequently improving the sensitivity of the humidity sensing. An energy band diagram is proposed to explain the experiment phenomenon of the humidity sensor. This work provides a simple way to enhance the sensitivity of ultrathin two-dimensional-materials-based sensors by the piezotronic effect, which has great potential applications in electronic skin, human–computer interfacing, gas sensing, and environment monitoring.

At present, concealed attacks such as exploit, generics, SQL injection and APT are becoming more and more serious, and shallow machine learning is no longer a good way to detect these hidden forms of attack. In this paper, an intrusion detection model based on principal component analysis optimization for Long Short Term Memory Networks is designed. The main principle is to remove the noise information in the sample data through principal component analysis, and utilize the memory function of Long Short Term Memory Networks and the powerful sequence data learning ability. The key issues of abnormal behavior detection combined with principal component analysis and Long Short-Term Memory Networks are studied in detail, including model structure, processing flow, hyperparameter analysis in LSTM and data preprocessing.

Background Immune dysregulation and organ damage are characteristic of systemic lupus erythematosus (SLE). We previously reported that mitochondrial reactive oxygen species (ROS) and the release of oxidized mitochondrial DNA (mtDNA) may be involved in autoimmunity and contribute to the generation of type I IFN responses, important mediators in the pathogenesis of SLE. Mitochondrial dysfunction and an imbalance in ROS production may lead to oxidative stress, mitochondrial lipid, protein and DNA modifications, and alterations in the production of adenosine triphosphate (ATP). Idebenone is a coenzyme Q10 synthetic analog with antioxidant properties previously tested in humans to treat different diseases where mitochondrial function is compromised. This study aimed to assess if idebenone mitigates murine lupus. Methods Two different doses of idebenone were given orally to MRL/lpr mice for 8 weeks. At euthanasia, treated and untreated mice were analyzed and compared for clinical, immunologic and metabolic parameters including autoantibody generation, proteinuria, kidney function and pathology, renal immune complex deposition, endothelium-dependent vasorelaxation, assessment of pro-inflammatory gene expression, quantification and characterization of neutrophil extracellular trap (NET) formation and mitochondrial ROS, measurement of complex II-specific activity and cardiac lipid peroxidation. Results Idebenone was well tolerated and led to significant attenuation in mortality and an improvement of glomerular inflammation, renal function, skin ulcers and splenomegaly. The levels of proinflammatory cytokines and inflammasome-related genes were significantly decreased by idebenone. In addition, we observed inhibition of NET formation both in lupus mice bone marrow neutrophils and in neutrophils from lupus patients. Enhanced complex II-specific activity and mitochondria specific gene transcription were shown in cells isolated from idebenone-treated lupus-prone mice, suggesting improved mitochondrial function and reduction of oxidative stress. Idebenone-treated mice also displayed reduced heart lipid peroxidation. Conclusions Idebenone improves murine lupus. These results suggest that idebenone and other drugs that improve mitochondrial function may have a therapeutic role in SLE. Funding Source(s): This study was supported by the Intramural Research Program, NIAMS/NIH (ZIA AR041199) and the Alliance for Lupus Research.

Low power and multifunctional nonvolatile memories are promising candidates for processing massive data in the Internet of Things era. However, the storage states in conventional memory devices are under the restricted control by electrical or optical signals. Herein, a new multibit tribotronic nonvolatile memory (T-NVM) based on a graphene/hexagonal boron nitride/molybdenum disulfide van der Waals heterostructure and triboelectric nanogenerator (TENG) is proposed. The programming/erasing states can be modulated by the triboelectric potential, which is determined by changing the distance between the two triboelectrification layers. Under the modulation of external mechanical actions, the device exhibits a high on/off ratio of 105 via manipulating mechanical distance from − 0.2 mm to + 0.2 mm, a long retention time up to 6000 s, a stable switching behavior for over 100 cycles, and a multilevel data storage capability of 14 stages by different external stimuli. Furthermore, a memory inverter circuit employing the triboelectric potential as input signals can serve as the conversion of logical signals. This work proves the great potential of tribotronic devices for direct interaction with external environment in lower power and broadening diverse applications of human-robot interactions, self-powered wearable devices, and intelligent instrumentation.

Flexible functional devices based on two dimensional (2D) materials are extremely suitable for malleable, portable and sustainable applications, such as health monitoring, electronic skin and optoelectronics. In this work, we developed a flexible photodetector based on a p-CuO/n-MoS2 heterojunction with an enhancement in photocurrent and detection sensitivity. Because of the non-centrosymmetric structure in monolayer MoS2, the piezo-potential induced by applied strain adjusts the band structure at the heterojunction interface and broadens the depletion region based on the piezo-phototronic effect. The border depletion can be discreetly used to improve the photo-generated carrier separation and transport to enhance photoresponse performance. When illuminated by a 532 nm laser, the photocurrent of the heterojunction can be enhanced 27 times under a tensile strain of 0.65% compared to strain free conditions and the detection sensitivity can reach up to 3.27 × 108 Jones. As a result, our research provides a new strategy for novel design and performance optimization of 2D material heterostructures in the application of optoelectronics.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with high mortality. Macrophages and neutrophils are responsible for inflammatory responses in ALI and ARDS, which are characterized by excessive production of proinflammatory mediators in bronchoalveolar lavage fluid (BALF) and plasma. Aberrant activation of the JAK/STAT pathway is critical for persistent inflammation in many conditions such as infection and autoimmunity. Given the importance of the STAT3 transcription factor in activating macrophages and neutrophils and augmenting inflammation, we investigated the therapeutic potential of inhibiting STAT3 activity using the small-molecule STAT3 inhibitor, LLL12. Our results demonstrate that LPS induces STAT3 activation in macrophages in vitro and in CD45+CD11b+ cells from BALF in the LPS-induced ALI model in vivo. LLL12 treatment inhibits LPS-induced lung inflammation in the ALI model, which is accompanied by suppression of LPS-induced STAT3 activation and an inhibition of macrophage and inflammatory cell infiltration in lung and BALF. LLL12 treatment also suppresses expression of proinflammatory genes including IL-1β, IL-6, TNF-α, iNOS, CCL2, and MHC class II in macrophages and inflammatory cells from BALF and serum as determined by ELISA. Furthermore, hyperactivation of STAT3 in LysMCre-SOCS3fl/fl mice accelerates the severity of inflammation in the ALI model. Both pre- and post-LPS treatment with LLL12 decrease LPS-induced inflammatory responses in mice with ALI. Importantly, LLL12 treatment attenuates STAT3 phosphorylation in human peripheral blood mononuclear cells induced by plasma from patients with ARDS, which suggests the feasibility of targeting the STAT3 pathway therapeutically for patients with ALI and ARDS.

Calcaneal fractures are rare in pediatric population, with more displaced intra-articular fractures encountered due to the increasing number of high-energy trauma. Operative interventions are gaining popularity because of the unsatisfactory outcomes of traditional conservative methods. This study investigated the clinical outcomes of a minimally invasive technique using the sinus tarsi approach and external fixator in the treatment of intra-articular calcaneal fractures in pediatric patients. Patients who underwent open reduction between January 2010 and January 2018 at our institute were included in this study and reviewed retrospectively. Radiological and clinical parameters were all recorded and analyzed. Overall, 29 patients were included in the study, including 23 boys and 6 girls (10.2 ± 2.2 years old). The average follow-up was 29.5 months postoperatively (range, 26–72 months). Bohler angle was 15.2 ± 3.3° preoperatively, and 34.0 ± 3.8° postoperatively (P

Active participation from human subjects can enhance the effectiveness of robot-assisted rehabilitation. Developing interactive control strategies for customized assistance is therefore essential for encouraging human-robot engagement. However, existing human-robot interactive control strategies lack precise evaluation indicators with effective convergence method to steadily and rapidly customize appropriate assistance during task-oriented training. This study proposes a performance-based iterative learning control algorithm for robot-assisted training, which aims at providing subject-specific robotic assistance to encourage active participation. Three performance indicators based on a Fugl-Meyer Assessment (FMA) regression model are introduced to associate clinical scales with robot-based measures, and a fuzzy logic is employed for comprehensive performance evaluation. To increase efficient training time, a piecewise learning rate based iterative law is applied to quickly converge to a subject-specific control parameter session by session. The proposed strategy is preliminarily estimated for a case of bilateral upper limb training with an end-effector based robotic system. Experimental results with human subjects indicate that the proposed strategy can obtain appropriate parameters after only several iterations and adapt to random perturbations (like muscle fatigue).

Introduction: Lateral condylar fracture (LCF) of the humerus in children is one of the commonest elbow injuries in children. Early recognition of the problem and appropriate management usually yields satisfactory outcomes. Closed or open reduction with Kirschner-wire (KW) is a cost-effective choice of fixation method for displaced fracture. However, various other methods, including partially threaded cannulated cancellous screw and biodegradable pin (BP), have also been used. This study aimed to investigate the efficacy of BP and compare its clinical outcomes with KW. Material and methods: Patients with LCF admitted from January 2008 to January 2016 at our institute were reviewed retrospectively. Baseline information and clinical data were collected from Hospital Database. Patients were divided into the KW group and BP group. Results: In all, 85 patients (male 50, female 35) in the KW group and 76 patients (male 47, female 29) in the BP group were included in this study. The average age of patients in the KW group was 5.2 years, and that of BP was 5.9 years. No nonunion or malunion was observed in either group. At the last follow-up visit, there was no statistically significant difference between the 2 groups with regard to elbow function and appearance. The incidence of long-term complications, including avascular necrosis, fishtail deformity, and lateral prominence, showed no significant difference between both the groups. The incidence of hardware prominence was higher in the KW (13/85, 15.6%) than BP (2/76, 2.6%) group (P

Background Self-assembling peptide scaffolds have been extensively applied in tissue engineering. Many investigations have modified self-assembling peptide scaffolds by integrating functional motifs, with promising applications. This study aimed to generate a novel RADA16 self-assembling peptide scaffold integrating a neural-cell adhesion molecule-derived mimetic-peptide (SIDRVEPYSSTAQ) and evaluated the effects on neuron proliferation. Material/Methods A 37-amino-acids peptide of RADA16-activation motif containing neural-cell adhesion molecule-derived mimetic-peptide (SIDRVEPYSSTAQ) was synthesized and self-assembled into a scaffold. Dorsal root ganglion (DRG) and spinal cord motor neurons (SCMN) were primarily isolated and identified. Neurons (DRG and SCMN) were divided into FRM, FRM-MP, and FRM-MP-LiCl groups. The adherence ability of neurons was evaluated using toluidine blue staining. Proliferation and apoptosis of neurons were assessed using CCK-8 and flow cytometry assay, respectively. Immunofluorescence assay was used to measure neurite extension. Western blot assay was used to assess GSK-3β/p-GSK-3β, Tau/p-Tau, and calpain expression in neurons. Results FRM-MP-LiCl released multiple-peptide with higher efficiency. FRM-MP-LiCl significantly enhanced proliferation and inhibited apoptosis compared to FRM and FRM-MP groups (p

Many of the state-of-the-art methods can only localize scene texts with rotated rectangle boundaries, which may result in incorrect rectification of the detected scene texts and erroneous elimination of proposals or detections during non-maximum suppression (NMS). A few existing methods that can detect scene texts with quadrilateral boundaries, are just based on one-stage architectures or sliding windows scanning and thus have sub-optimal performance. To address these problems, we propose an end-to-end two-stage network architecture for scene text detection, which can accurately localize scene texts with quadrilateral boundaries. At the first stage, we propose a quadrilateral region proposal network (QRPN) for generating quadrilateral proposals, based on a newly proposed quadrilateral regression algorithm. At the second stage, we introduce a novel weighted RoI pooling module with learned weight masks to pool the features, and then classify the proposals and refine their shapes with the proposed quadrilateral regression algorithm again. Specially, during training, we adopt a dual-branch structure of detection heads, that is, jointly train the quadrilateral detection head and an additional rotated rectangle detection head. Furthermore, we develop an accelerated NMS algorithm with O(nlogn) complexity, for redundant quadrilateral text proposals and detections eliminating during the first and the second stage, respectively. Experiments on several challenging benchmarks demonstrate the superior performance of the proposed method, which achieves state-of-the-art results on widely used benchmarks ICDAR 2017 MLT, RCTW, and ICDAR 2015 Incidental Scene Text benchmark.

Background Cancer is the leading cause of death in the developed world, and yet healthcare practitioners infrequently discuss goals of care (GoC) with hospitalized cancer patients. We sought to identify barriers to GoC discussions from the perspectives of staff oncologists, oncology residents, and oncology nurses. Methods This was a single center survey of staff oncologists, oncology residents, and inpatient oncology nurses. Barriers to GoC discussions were assessed on a 7-point Likert scale (1 = extremely unimportant; 7 = extremely important). Results Between July 2013 and May 2014, of 185 eligible oncology clinicians, 30 staff oncologists, 10 oncology residents, and 28 oncology nurses returned surveys (response rate of 37%). The most important barriers to GoC discussions were patient and family factors. They included family members’ difficulty accepting poor prognoses (mean score 5.9, 95% CI [5.7, 6.2]), lack of family agreement in the goals of care (mean score 5.8, 95% CI [5.5, 6.1]), difficulty understanding the limitations of life-sustaining treatments (mean score 5.8, 95% CI [5.6, 6.1]), lack of patients’ capacity to make goals of care decisions (mean score 5.7, 95% CI [5.5, 6.0]), and language barriers (mean score 5.7, 95% CI [5.4, 5.9]). Participants viewed system factors and healthcare provider factors as less important barriers. Conclusions Oncology practitioners perceive patient and family factors as the most limiting barriers to GoC discussions. Our findings underscore the need for oncology clinicians to be equipped with strong communication skills to help patients and families navigate GoC discussions. Electronic supplementary material The online version of this article (10.1186/s12885-019-5333-x) contains supplementary material, which is available to authorized users.

Smart energy textiles based on triboelectric nanogenerators (TENGs) are promising power supply and sensor arrays for wearable electronics and artificial intelligence. However, the challenges of the smart textile in large-scale industrialized production, facile and universal fabrication process, and enough robustness still remains. In this study, a textile-based triboelectric nanogenerator (t-TENG) is proposed through a facile and universal fabrication process. Liquid-metal/polymer core/shell fibers (LCFs) structure as the basic unit of TENG textiles, can be extensively achieved by pumping liquid metal into uniform ultrafine polymer hollow fibers, which contribute to the large-scale industrialized production of TENG textiles. In addition to gaining a high output, the t-TENG demonstrates excellent acid and alkali resistance, and high friction durability. Furthermore, profiting from the universal fabrication process, the polymer hollow fibers can be replaced by any type of fibers with various functions or colors according to practical applications (e.g., the silicone rubber could be an excellent choice for highly stretchable devices). Moreover, the fabricated t-TENGs demonstrate great capability in self-powered sensors for smart home controlling. All these advantages of the t-TENG exhibit its great potential for further application in wearable electronics and artificial intelligence and it will speed up the development of IoTs in the near future.

Over the past several decades, it has been well recognized that systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic vascular disease. The pathogenic mechanisms leading to this complication are complex and associated with the profound immune dysregulation characteristic of SLE. This chapter highlights the putative mechanisms promoting premature vascular damage in lupus and discusses potential therapeutic targets.

Hematoxylin and Eosin H&E stained breast tissue samples from biopsies are observed under microscopy for the gold standard diagnosis of breast cancer. However, a substantial workload increases and the complexity of the pathological images make this task time-consuming and may suffer from pathologist’s subjectivity. Facing this problem, the development of automatic and precise diagnosis methods is challenging but also essential for the field. In this paper, we propose a new hybrid convolutional and recurrent deep neural network for breast cancer pathological image classification. Our method considers the short-term as well as the long-term spatial correlations between patches through RNN which is directly incorporated on top of a CNN feature extractor. Experimental results showed that our method obtained an average accuracy of 90.5% for 4-class classification task, which outperforms the state-of-the-art method. At the same time, we release a bigger dataset with 1568 breast cancer pathological images to the scientific community, which are now publicly available from http://ear.ict.ac.cn/?page id=1576. In particular, our dataset covers as many different subclasses spanning different age groups as possible, thus alleviating the problem of relatively low classification accuracy of benign.

We evaluated the clinical performance of anti-CEP-1 in a Chinese rheumatoid arthritis (RA) cohort. A total of 264 subjects were tested, including 101 RA patients, 38 juvenile idiopathic arthritis (JIA) patients, 46 disease control (DC) and 79 healthy controls (HC). The presence of anti-CEP-1 in patients with RA, JIA, DCs and HC were 61.4%, 13.2%, 15.2% and 5.1%, respectively. Anti-CCP2 demonstrated the highest positive likelihood ratio of 10.11 in the diagnosis of RA, followed by RF (8.88) and anti-CEP-1 (5.82). Anti-CEP-1 positive RA patients displayed significantly higher DAS28 compared to anti-CEP-1 negative RA patients (p = .045). Significant associations were identified between anti-CEP-1 and joint erosions at anti-CEP-1 value of >124.78 U/ml (p = .0026) and between anti-CEP-1 and ILD at anti-CEP-1 value of >185.91 U/ml (p = .0222). Our findings indicate that anti-CEP-1 may not be able to replace anti-CCP2 for routine diagnosis for RA, but they may be helpful for subtyping of the disease.

By using the ANSYS model, this paper studied the fluence caused by tension control stress, ratio of reinforcement, ratio of CFRP bar and concrete strength on stress increment of concrete bridge deck unbonded partially prestressed with CFRP bars. A formula was fitted out about the relationship between the ultimate stress increment of CFRP tendons and comprehensive reinforcement parameter(β0).

Due to the limited computational resources of data owners and the developments in cloud computing, more and more data owners choose to store data on the cloud to reduce their own storage burden. When the data owner wants to re-select a new cloud service provider, the data needs to be transmitted from Cloud A to Cloud B. How to ensure that data has been safely transferred to Cloud B and Cloud A honestly implementing data deletion has become a hot topic for many scholars. To solve these problems, Liang et al. proposed a provable data transfer protocol based on provable data possession and deletion for secure cloud storage. However, we find a security flaw in their scheme. In this paper, we first review their scheme and then present our attack in detail. Finally, we propose an improved scheme which can resist the attack well.