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Firm survival in dynamic software markets depends on collaboration with ecosystem complementors and exploitative and/or explorative innovation. Such activities have been widely accepted as crucial antecedents for collaboration success, but few studies have analyzed the configurational effects of collaborative modes effect on firm performance. Based on a sample of 224 software firms and fuzzy set qualitative comparative analysis, results show that four causal configurations equivalently explain high innovation performance, in which exploitation, exploration, and collaboration with academic and governmental institutes are proven to be core causal conditions. Theoretically, this article contributes to the literature on collaborative innovation in terms of causality research and collaborative pathways but also enriches the literature on software ecosystems regarding partnerships and collaborative processes. Practical guidance and flexible choices for software firms to achieve high innovation performance are provided by offering four equivalent configurations.

Background: Spinal muscular atrophy (SMA) is a common neuromuscular disorder, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Population-wide SMA screening to quantify copy number of SMN1 is recommended by multiple regions. SMN1 diagnostic assay with simplified procedure, high sensitivity and throughput is still needed.Methods: Real-Time PCR with High-Resolution Melting for the quantification of the SMN1 gene exon 7 copies and SMN1 gene exon 8 copies was established and confirmed by multiplex ligation-dependent probe amplification (MLPA). The diagnosis of 2563 individuals including SMA patients, suspected cases and the general population were analyzed by the real-time PCR. The results were compared with the gold standard test MPLA. Results: In this study, the homozygous deletions, heterozygous deletions were identified by Real-Time PCR with High-Resolution Melting method with an incidence of 10.18% and 2.42%, respectively. In addition, the R value distribution (P>0.05) among the 8 replicates and the coefficient of variation (CVConclusions: The qPCR based on High-Resolution Melting provides a sensitive and high-throughput approach to large-scale SMA carrier screening with low cost and labor.

The kernel principal component analysis (KPCA) is widely used as a fault monitoring tool for complex nonlinear chemical processes in recent years. The cumulative contribution rate that extracts the kernel principal is usually obtained relied on a fixed model, which cannot be employed for time-varying chemical processes. Hence, a novel adaptive kernel principal component analysis (AKPCA) integrating grey relational analysis (GRA) (AKPCA-GRA) is proposed to dynamically monitor the fault occurrence. A moving window integrating the threshold method is used to adaptively extract the kernel principal for chemical processes. Then the corresponding T2 and Q statistics calculated by the selected kernel principal based on the AKPCA decides whether the fault has occurred. Moreover, the GRA method is used to analyze and calculate the correlation coefficient of abnormal features obtained based on the APKCA method, which provides the operational guidance for the nonlinear chemical process to find out the variable causing the fault. Finally, the proposed method is verified using the Tennessee Eastman (TE) process. The case results demonstrate that the proposed method outperforms the KPCA, the KPCA based on the threshold and the moving window principal component analysis, the support vector machine (SVM) and the Logistic Regression (LR) in terms of the missed alarm rate (MAR) and the false alarm rate (FAR), which can effectively analyze the variables causing the fault.

Multisource synthetic aperture radar (SAR) image registration is a difficult task in remote sensing due to the influence of speckle noise and geometric distortions between the images. The SAR scale-invariant feature transform (SAR-SIFT) is a prior option to extract features for automatic registration of SAR images. However, most registration methods based on the SAR-SIFT operator only use the image information (the geometric distribution of the pixels making up the feature) and do not consider the influences of the side-looking imagery mode and the topographic relief. In this article, we propose a novel registration method to address the above problems, which combines the optimized SAR-SIFT features and the imaging geometry of the SAR system. The major improvement of the algorithm is the use of the range-Doppler (RD) model in feature matching and geometric transformation estimation. A new local matching method aided by the RD model, transforming the global matching mode to the local one, is first introduced to avoid the gross errors and improve the matching efficiency. Then, an RD-model-based geometric transformation model is presented for multisource SAR images with obvious geometric distortions. In addition, the stationary wavelet transform (SWT) is brought in the feature extraction to optimize the SAR-SIFT keypoints to extract reliable and uniformed features. The experimental results fully demonstrate the applicability of the proposed method for registration of multisource SAR images in different acquiring configurations, especially with different passes.

Aiming at solving the problems of bad imperceptibility and low embedding rate of existing algorithms, a novel large-capacity reversible image watermarking based on improved difference expansion (DE) is proposed. Firstly, the smoothness calculation algorithm is used to calculate and sort the smoothness values of the divided image sub-blocks; then, the scrambled watermark is embedded into the sub-blocks with less smoothness after removing the abrupt point by using the generalized difference expansion (GDE); finally, the absolute difference operation is applied to the generated overflow pixels to make their pixel values within a reasonable range for embedding watermark information. Under the premise of ensuring a certain visual quality, multiple watermark embedding can effectively improve the embedding rate. The simulation results show that this algorithm not only realizes blind extraction, but also recovers the original images without loss. At the same time, this algorithm achieves a high embedding rate (the average embedding rate is as high as 77.91 dB) without decreasing the visual quality.

Background It is well known that the thalamus is not a unitary and homogeneous entity but a complex and highly connected archeocortical structure. Although many neuroimaging studies have reported alterations in the thalamus in major depressive disorder (MDD), the structural alterations in thalamic subfields remain unclear. This study aimed to investigate changes in gray matter volume (GMV) in thalamic subfields in MDD patients. Methods The present study included structural images of 848 MDD patients and 794 age-matched normal controls (NC) from 17 study sites of the REST-meta-MDD consortium. We performed voxel-based morphometric analyses to calculate the GMV in the entire thalamus and its subfields using three different automated anatomical labeling atlases and subsequently compared the differences between first-episode drug-naive major depressive disorder (FEDN), recurrent major depressive disorder (RMDD), and NC groups. We also evaluated the relationships between thalamic GMV and clinical symptoms in MDD patients. Results Compared to NC, the FEDN patients showed increased GMV in thalamic subfields but not in the entire thalamus, while RMDD patients showed no significant alterations in GMV in the entire thalamus and its subfields. Moreover, the mean GMV in the right anterior thalamus and left anteroventral thalamus in RMDD patients were mildly positively correlated with the Hamilton Anxiety Rating Scale scores. Limitations The main limitations are a single-modal analysis based on T1-weighted MR images and a cross-sectional design. Conclusions Our findings suggest that FEDN and RMDD patients show heterogeneous alterations across thalamic subfields, which may help us understand the pathophysiological mechanisms of MDD.

In all parts of the world, water is rapidly becoming an emerging issue. Mature technologies had been established in the water treatment process to overcome the issue. However, the water treatment technology advance does not mean it is not faced with its issues. In fact, it still leaves many problems for humans due to both technical issues and management problems. Understanding the water treatment process's proper perspective is required to achieve sustainable and equitable development for Muslim countries. In the other hand, Islam endeavors comprehensive guidelines on all aspects of human life and manages water resources. This mini-review article will give a brief explanation of some excellent technologies of water treatment and challenges associated with the advancing control over their beneficiation. Therefore, an Islamic perspective will be addressed to emphasize how Islamic-based policy and management can take a leading solution to overcome the fundamental problem for the future of water for the benefit of human life.

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity., Brown adipocytes contribute to energy balance, and adipocyte development and brown adipocyte thermogenesis are in part regulated by epigenetic modifications. Here the authors report that the histone demethylase Utx maintains brown adipocyte identity via demethylation of PRDM16, which in turn represses myogenic remodelling via DNMT1-mediated Myod1 promoter hypermethylation in mice.

Background Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear. Research Question Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations? Study Design and Methods This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost. Results A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027). Interpretation Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT02147015; URL: www.clinicaltrials.gov

Background The clinicopathological predictors of sentinel lymph node (SLN) metastasis in clinical T1-T2 N0 (cT1-T2 N0) patients with a normal axillary ultrasound (AUS) are unclear. Purpose To assess the association between clinicopathological characteristics of a primary tumor and SLN metastasis in cT1-T2 N0 patients with a normal AUS. Material and Methods Patients who were diagnosed with cT1-T2 N0 invasive breast cancer and who obtained normal AUS results between October 2016 and September 2018 in a single hospital were included. Clinicopathological data were collected to explore the predictors of SLN metastasis using a multivariate logistic regression model. Results SLN metastasis occurred in 26 patients (18.4%) among 141 AUS-normal patients, of which 24 cases (17.0%) had one or two nodal involvements. In the univariate analysis, tumor location, estrogen receptor (ER) status, progesterone receptor (PR) status, and lymphovascular invasion (LVI) were significantly associated with SLN metastasis ( P Conclusion Tumor location in the upper outer quadrant, positive PR, and LVI status were found to be significantly high-risk factors for SLN metastasis among cT1-T2 N0 breast cancer patients with a normal AUS result.

PURPOSE To investigate the corneal endothelium damage in Graves ophthalmopathy (GO) and its role as a promising quantitative index to evaluate GO activity. DESIGN Cross-sectional study. METHODS This study included 128 eyes of 64 patients with GO. All subjects underwent ophthalmologic examinations, including proptosis, tear break-up time (BUT), corneal fluorescein staining, and Schirmer test. Corneal endothelium was measured by noncontact specular microscope and ocular biometric parameters were measured by IOLMaster 700. Each eye was assigned a specific clinical activity score (CAS), then grouped as active (CAS ≥3 points) or inactive (CAS

Accurate assessment of mitral regurgitation (MR) severity is critical in clinical diagnosis and treatment. No single echocardiographic method has been recommended for MR quantification thus far. We sought to define the feasibility and accuracy of the mask regions with a convolutional neural network (Mask R-CNN) algorithm in the automatic qualitative evaluation of MR using color Doppler echocardiography images. The authors collected 1132 cases of MR from hospital A and 295 cases of MR from hospital B and divided them into the following four types according to the 2017 American Society of Echocardiography (ASE) guidelines: grade I (mild), grade II (moderate), grade III (moderate), and grade IV (severe). Both grade II and grade III are moderate. After image marking with the LabelMe software, a method using the Mask R-CNN algorithm based on deep learning (DL) was used to evaluate MR severity. We used the data from hospital A to build the artificial intelligence (AI) model and conduct internal verification, and we used the data from hospital B for external verification. According to severity, the accuracy of classification was 0.90, 0.89, and 0.91 for mild, moderate, and severe MR, respectively. The Macro F1 and Micro F1 coefficients were 0.91 and 0.92, respectively. According to grading, the accuracy of classification was 0.90, 0.87, 0.81, and 0.91 for grade I, grade II, grade III, and grade IV, respectively. The Macro F1 and Micro F1 coefficients were 0.89 and 0.89, respectively. Automatic assessment of MR severity is feasible with the Mask R-CNN algorithm and color Doppler electrocardiography images collected in accordance with the 2017 ASE guidelines, and the model demonstrates reasonable performance and provides reliable qualitative results for MR severity.

Social interaction is an important factor for many mobile applications, including mobile public welfare applications (MPWAs), to successfully attract users to keep using them. We explored the influence mechanism of social interaction on users' continuance of usage behavior in relation to MPWAs by constructing an interaction–experience–intention influence path. A survey was designed and distributed on QQ, WeChat moments, and via WeChat groups. Using this snowball sampling method, we collected 362 completed surveys. To test the research hypotheses we used structural equation modeling and hierarchial regression analysis. The results show that social interaction affected social presence positively, and social presence had a significant influence on emotional pleasure and continued usage intention. Emotional pleasure positively affected continued usage intention. Shared vision played a moderating role in the relationship between social presence and continued usage intention. These conclusions enrich the literature on social presence and personal participation in public welfare in the context of mobile applications, and also provide some useful suggestions for MPWA managers on how to ensure continued usage.

High complexity and low recognition rate are two common problems with the current finger vein recognition methods. To solve these problems, this paper integrates two-dimensional kernel principal component analysis (K2DPCA) plus two-dimensional linear discriminant analysis (2DLDA) (K2DPCA+2DLDA) into convolutional neural network (CNN) to recognize finger veins. Considering the row and column correlations of the finger vein image matrix and the classes of finger vein images, the authors adopted K2DPCA and 2DLDA separately for dimensionality reduction and extraction of nonlinear features in row and column directions, producing a dimensionally reduced compressed image without row or column correlation. Taking the dimensionally reduced compressed image as the input, the CNN was introduced to learn higher-level features, making finger vein recognition more accurate and robust. The public dataset of Finger Vein USM (FV-USM) Database was adopted for experimental verification. The results show that the proposed approach effectively overcome the common defects of original image feature extraction: the insufficient feature description, and the redundancy of information. When the training reached 120 epochs, the model basically realized stable convergence, with the loss approaching zero and the recognition rate reaching 97.3%. Compared with two-directional two-dimensional Fisher principal component analysis ((2D)2FPCA), our strategy, which integrates K2DPCA+2DLDA with CNN, achieved a very high recognition rate of finger vein images.

Objective Depression and resilience are different psychological outcomes caused by experiencing traumatic events. We aimed to 1) explore heterogeneity patterns of co-occurrence between depression symptoms and resilience among children and adolescents exposed to an earthquake and 2) assess covariates (trauma exposure, sex, age, ethnicity, and sleep quality) in identifying the best fitting solution. Methods Latent profile analysis (LPA) was used to examine patterns of self-reported depression and resilience in an epidemiological sample of 2,887 Chinese youth survivors 1 year after the Lushan earthquake. Results A suitable 3-class model were identified, which are mild depression/high resilience (65.0%), severe depression/high resilience (22.1%), and severe depression/low resilience (12.9%). Trauma exposure, demographic characteristics and sleep state can be used to identify the different latent classes. Conclusion Our results contribute to understanding the heterogeneous coexisting patterns of depression and resilience and provide suggestions for identifying high-risk youth survivors and offering effective interventions.

Natural image matting is an important problem that widely applied in computer vision and graphics. Recent deep learning matting approaches have made an impressive process in both accuracy and efficiency. However, there are still two fundamental problems remain largely unsolved: 1) accurately separating an object from the image with similar foreground and background color or lots of details; 2) exactly extracting an object with fine structures from complex background. In this paper, we propose an attention transfer network (ATNet) to overcome these challenges. Specifically, we firstly design a feature attention block to effectively distinguish the foreground object from the color-similar regions by activating foreground-related features as well as suppressing others. Then, we introduce a scale transfer block to magnify the feature maps without adding extra information. By integrating the above blocks into an attention transfer module, we effectively reduce the artificial content in results and decrease the computational complexity. Besides, we use a perceptual loss to measure the difference between the feature representations of the predictions and the ground-truths. It can further capture the high-frequency details of the image, and consequently, optimize the fine structures of the object. Extensive experiments on two publicly common datasets ( i.e. , Composition-1k matting dataset, and www.alphamatting.com dataset) show that the proposed ATNet obtains significant improvements over the previous methods. The source code and compiled models have been made publicly available at https://github.com/ailsaim/ATNet .

Glioma pathogenesis-related protein 1 (GLIPR1) was identified as an oncoprotein in some cancer types including gliomas, breast cancers, melanoma cancers, and Wilms tumors, but as a tumor suppressor in some other types of cancers, such as prostate cancers, lung cancers, bladder cancers, and thyroid cancers. In gliomas, GLIPR1 promotes the migration and invasion of glioma cells by interaction with the actin polymerization regulator Neural Wiskott-Aldrich syndrome protein (N-WASP) and then abolishes the negative effects of Heterogeneous nuclear ribonuclear protein K (hnRNPK). In prostate cancers, high levels of GLIPR1 induce apoptosis and destruction of oncoproteins. In lung cancers, overexpression of GLIPR1 inhibits the growth of lung cancer cells partially through inhibiting the V-ErbB avian erythroblastic leukemia viral oncogene homolog3 (ErbB3) pathway. However, the mechanisms that GLIPR1 performs its function in other tumors still remain unclear. The tumor suppressing role of GLIPR1 has been explored to the cancer treatment. The adenoviral vector-mediated Glipr1 (AdGlipr1) gene therapy and the GLIPR1-transmembrane domain deleted (GLIPR1-ΔTM) protein therapy both showed antitumor activities and stimulated immune response in prostate cancers. Whether GLPIR1 can be used to treat other tumors is an important topic to be explored. Among which, whether GLPIR1 can be used to treat lung cancer by atomizing inhalation is the key topic we care about. If it does, this therapy has a wide application prospect and is a great progression in lung cancer treatment.

Gestational exposure to PM2.5 is associated with adverse postnatal outcomes. PM2.5 can enter alveoli by using intratracheal instillation, even penetrate through lung cells into the blood circulation. Subsequently, they are transferred across the placenta and fetal blood brain barrier, causing the adverse birth outcomes of offspring. This study demonstrated that the gestational exposure resulted in cognitive and emotional disorders in female offspring although the offspring were not exposed to PM2.5. Placental metabolic pathways modulated fetal brain development and played a pivotal role for maternal-placental-fetal interactions in the fetal programming of adult behavioral and mental disorders. Samples of fetus, offspring hippocampus and placenta from the mice exposed to PM2.5 were investigated using a comprehensive approach including mass spectrometry-based lipidomics and three-dimensional imaging. The exposure induced the neuro-degeneration in hippocampus, impairment of placental cytoarchitecture, and reprogramming of lipidome, which might affect the modulation of maternal-fetal cross-talk and result in the behavior disorders of offspring. The variation of spatial distribution of lipids was profoundly affected in dorsal pallium and hippocampal formation regions of fetal brain, offspring hippocampus, as well as labyrinth and junctional zones of placenta. The abundance alteration of lipid markers associated with neurodegenerative diseases was validated in transgenic mouse model with Alzheimer’s disease and human cerebrospinal fluid from patients with Parkinson’s disease. The finding could help with the selection of more suitable heterogeneous-related substructures targeting PM2.5 exposure and the exploration of PM2.5-induced toxicological effects on neurodegenerative diseases.

Respiratory syncytial virus (RSV) is leading cause of respiratory tract infections in early childhood. Gut microbiota is closely related with the pulmonary antiviral immunity. Recent evidence shows that gut dysbiosis is involved in the pathogenesis of RSV infection. Therefore; pharmacological and therapeutic strategies aiming to readjust the gut dysbiosis are increasingly important for the treatment of RSV infection. In this study, we evaluated the therapeutic effects of a probiotic mixture on RSV-infected mice. This probiotic mixture consisted of Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3 was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection. We showed that administration of the probiotics protected against RSV-induced lung pathology by suppressing RSV infection and exerting an antiviral response via alveolar macrophage (AM)-derived IFN-β. Furthermore, administration of the probiotics reversed gut dysbiosis and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice, which consequently led to elevated serum SCFA levels. Moreover, administration of the probiotics restored lung microbiota in RSV-infected mice. We demonstrated that the increased production of IFN-β in AMs was attributed to the increased acetate in circulation and the levels of Corynebacterium and Lactobacillus in lungs. In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in future. [Image: see text]

Aim Depression and anxiety are both common psychological outcomes triggered via trauma-related experience. The current study aimed to identify the prevalence of depression and anxiety among youth survivors, explore the heterogeneity patterns of depression and anxiety symptoms in the chronic phase, and integrate early available information to predict patterns. Methods The study is a longitudinal study conducted at 2 weeks and 12 months after the Lushan earthquake. Finally, 1725 children and adolescents' survivors who accomplished both two-time stages assessments were included. The heterogeneous patterns of depression and anxiety symptoms assessed by latent profile analysis (LPA) were used to predict heterogeneity patterns of depression and anxiety symptoms by early attained variables. Results A three-class solution characterized mild depression/mild anxiety (64.3%), moderate depression/moderate anxiety (25.9%), and high depression/high anxiety (9.8%) parallel patterns was the most suitable model in our research. Demographic characteristics, earthquake-related exposures, sleep, and somatic symptoms were variables that can be used to predict the parallel profiles. Conclusions Detection of heterogeneity patterns, especially for youth survivors at high risk, based on the self-reported measurement attained at the early stage, is feasible. Our study may promote operational strategies by enabling targeted intervention.

Cross-efficiency in data envelopment analysis is widely used for performance evaluation of decision-making units (DMUs), but it neglects the reference relationship between each pair of DMUs. In order to address the problem, this paper introduces the concept of social network to clearly describe the reference relationship between DMUs and then a fully ranking can be made. A novel cross-efficiency approach is developed by integrating social network analysis in this study. Firstly, we propose a pairwise comparison model based on cross-efficiency evaluation to identify the superiority and inferiority between any pair of DMUs. Secondly, based on pairwise comparison, we build a non-weighted directed social network where a direction generates from one DMU to another DMU if the former one references the latter one. Each edge in the unweighted social network captures the learning procedure from worse-performance DMU to better-performance DMU. Comparing with traditional cross-efficiency approaches, our proposed approach considers the reference relationship among DMUs rather than only cross-efficiency scores. Thus, the importance of each DMU in the network can be measured by its centrality. Finally, the proposed approach is employed to environmental efficiency evaluation of the cities along the Xiangjiang River Basin, then, some beneficial universal policies have been summarized.

Background Infectious disease is the leading cause of fever of unknown origin (FUO). Serum inflammatory markers historically used to diagnose bacterial infection have sufficient diagnostic sensitivity but low specificity. This study aimed to develop a simple scoring system for differentiating bacterial infections from other causes of early-stage FUO. Methods This study included a retrospective cohort of patients presenting with FUO at the Huashan Hospital (January 2014 to June 2017). The diagnostic utility of serum inflammatory markers for bacterial infection was evaluated using the receiver operating characteristic (ROC) curve analysis. Relevant markers were subsequently measured prospectively in a separate cohort of FUO patients (December 2017 to May 2019). A scoring system was based on inflammatory markers and other test results. Results Bacterial infection was identified in 34% of patients in the retrospective cohort. The area under the ROC curve (AUC) was 0.644 (95% confidence interval [CI], .595–.693) for C-reactive protein, 0.624 (95% CI, .573–.675) for procalcitonin, and 0.646 (95% CI, .595–.697) for serum ferritin (SF) in diagnosing bacterial infection. Bacterial infection was found in 29% of cases in the prospective cohort. A model based on serum amyloid A (SAA) and SF levels and neutrophil percentage yielded an AUC of 0.775 (95% CI, .695–.854). Validation analysis indicated lower probability ( Conclusions A scoring system based on SAA and SF levels and neutrophil percentage can help distinguish bacterial infection from other causes of FUO, potentially reducing antibiotic use.

Background The outbreak of the 2019 novel coronavirus disease (COVID-19) not only caused physical abnormalities, but also caused psychological distress, especially for undergraduate students who are facing the pressure of academic study and work. We aimed to explore the prevalence rate of probable anxiety and probable insomnia and to find the risk factors among a longitudinal study of undergraduate students using the approach of machine learning. Methods The baseline data (T1) were collected from freshmen who underwent psychological evaluation at two months after entering the university. At T2 stage (February 10th to 13th, 2020), we used a convenience cluster sampling to assess psychological state (probable anxiety was assessed by general anxiety disorder-7 and probable insomnia was assessed by insomnia severity index-7) based on a web survey. We integrated information attained at T1 stage to predict probable anxiety and probable insomnia at T2 stage using a machine learning algorithm (XGBoost). Results Finally, we included 2009 students (response rate: 80.36%). The prevalence rate of probable anxiety and probable insomnia was 12.49% and 16.87%, respectively. The XGBoost algorithm predicted 1954 out of 2009 students (translated into 97.3% accuracy) and 1932 out of 2009 students (translated into 96.2% accuracy) who suffered anxiety and insomnia symptoms, respectively. The most relevant variables in predicting probable anxiety included romantic relationship, suicidal ideation, sleep symptoms, and a history of anxiety symptoms. The most relevant variables in predicting probable insomnia included aggression, psychotic experiences, suicidal ideation, and romantic relationship. Conclusion Risks for probable anxiety and probable insomnia among undergraduate students can be identified at an individual level by baseline data. Thus, timely psychological intervention for anxiety and insomnia symptoms among undergraduate students is needed considering the above factors.

The onset of depression and anxiety during the antenatal stage of pregnancy is common. Despite the conception of numerous interventions in the past decades, studies show no signs of decline in the prevalence of antenatal depression and anxiety. Recently, the use of midwife-supported psychotherapy to treat these psychosomatic disorders has garnered a lot of attention. However, no attempt to date has been made to synthesize the evidence evaluating the influence of midwife-supported psychotherapy on antenatal depression, anxiety, and overall maternal health-status. The aim of the present meta-analysis was to demonstrate the effectiveness of midwife-supported psychotherapy on depression, anxiety, and maternal health-status outcome during the antenatal stage of pregnancy. A systematic identification of literature was performed according to PRISMA guidelines on four academic databases: MEDLINE, Scopus, EMBASE and CENTRAL. A meta-analysis evaluated the influence of midwife-supported psychotherapy on depression, anxiety, and maternal health-status outcome as compared to conventional obstetric care. Of the 1,011 records, 17 articles, including 6,193 pregnant women (mean age: 28.9±2.2 years) were included in this meta-analysis. Eleven studies compared the effects of midwife-supported therapy on depression, 14 compared its effects on anxiety and 2 compared its effects on maternal health-status outcome. The meta-analysis reveals the beneficial effects of midwife-supported psychotherapy for reducing depression (Hedge's g: -0.9), anxiety (-0.8) and enhancing maternal health-status outcome (0.1), as compared to conventional obstetric care. The current systematic review and meta-analysis recommend the use of midwife-supported psychotherapy for the reduction of depression, anxiety and enhancing maternal health-status during the antenatal stage of pregnancy.

Objectives The rate of dermal toxicity has been shown to increase in patients receiving pegylated liposomal doxorubicin (PLD), particularly palmar-plantar erythrodysesthesia (PPE). However, it is difficult to diagnose and treat PLD-related PPE due to its delayed dermal performance, unclear pathogenetic mechanism, and the lack of specific preventive measures. The aim of this study was to provide potential management strategies for PPE associated with PLD. Methods The current article reviews the available data regarding the pharmacological and clinical aspects of PLD, including the formulation and pharmacokinetics of PLD, dose and schedule contribution to PPE, concomitant drugs affecting skin toxicity of PLD, the pathogenesis of PPE, and preventive measures and treatment of PLD-related PPE. Results The long circulation structure of polyethylene glycol liposomes may be one of the reasons for PPE. PLD has radically different pharmacokinetic characteristics, including prolonged blood circulation time, decreased body distribution volume, and slow clearance. Altering the schedules and doses of PLD or combining it with platinum compounds can optimise clinical efficacy and minimise the occurrence of PPE. Doses of 150–200 mg of pyridoxine daily have been widely used for the prevention and treatment of PPE. Regional cooling and plasma filtration have been used for PPE prophylaxis. Conclusions To date, the mechanism of PPE induced by PLD remains unclear, and no complete preventive medication has been established. Further research and prospective randomised studies are needed to understand the management options in PLD-related PPE.

PurposeInnovative use of enterprise systems (ES) by employees is essential for organisations to benefit from huge investments in such systems. Drawing on job demands-resources (JDR) theory, this study explores how stressors (i.e. challenge and hindrance stressors) influence employees' innovative use of ES, as well as considering the moderating effects of IT mindfulness.Design/methodology/approachData were collected from a longitudinal survey of 152 employees in a large financial service company in China. Hierarchical multiple regression was used to test the research model.FindingsResults showed that challenge stressors exerted a positive effect and hindrance stressors had no significant effect on innovative use of ES. Furthermore, we found that IT mindfulness weakened the positive effect of challenge stressors and the negative effect of hindrance stressors on innovative use of ES.Originality/valueThis study is among the first to extend the research of innovative use of ES by considering two types of stressors based on the JDR theory. Besides, new insights are provided on how to promote employees' innovative use of ES in the post-acceptance stage according to the different levels of IT mindfulness of employees.

Objective: Acupuncture combined with moxibustion (AM) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The present study aimed to confirm the effect and mechanism of AM treatment on the recovery of SCI. Design: Male Sprague–Dawley rats were used to establish the SCI model by impact method. SCI rat models were subjected to AM treatment at Dazhui (GV14) and Jiaji points (T7-T12), Yaoyangguan (GV3), Zusanli (ST36) and Ciliao (BL32). Outcome measures: Motor function and cell apoptosis in rats after SCI. The mRNA and protein expression levels of Shh and Gli-1 were determined by real-time quantitative polymerase chain reaction, western blot and immunohistochemistry. Results: After AM treatment, the hindlimb motor function of SCI rats was significantly increased than the SCI group at 7, 9, 11, 14 days (P

Background. Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. Methods. From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR≤2.74, 2.743.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. Results. During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR=1.39, 95%CI=1.01‐1.93, P=0.046) and CVD mortality (HR=1.81, 95%CI=1.22‐2.69, P=0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P<0.001) and CVD mortality (P=0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95%CI=1.26−3.23, P=0.003) and CVD mortality was 2.98 (95%CI=1.58−5.62, P=0.001) in the younger group (age<60 years). Conclusions. NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old.

With the popularity of social media, firms are prone to relying on the existing customers’ social contacts to acquire new customers. Referral reward programs (RRPs) have become one of the most effe...

Background Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC and to explore its related mechanisms. Methods The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cell apoptosis was induced by nutrient-deficient culture medium and detected by Cell Counting Kit-8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection. Results HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage, and lymph node metastasis. Compared with the low HIF1A-AS1 group, the high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines and was increased with the prolongation of nutrient-free culture. Inhibition of HIF1A-AS1 promoted starvation-induced HCC cell apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cell autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition. Conclusions HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy, promoting HCC cell progression.

Although neutrophil-to-lymphocyte ratio (NLR) is closely associated with pneumonia in the general population, its relationship is unclear in peritoneal dialysis (PD) patients. This is a cohort study consisting of 739 PD patients and dividing into two groups. Kaplan–Meier curves were applied to observe the incidence of the first occurrence of pneumonia, competitive risk analysis was conducted to compare whether there was a significant difference in each NLR group in the presence of other competing events, multivariable COX regression analysis was used to evaluate the hazard ratios (HRs), as well as forest plot was used to analyze the relationship between NLR and the first occurrence of pneumonia in different subgroups. Of all the patients, 116 cases of first-time pneumonia were recorded. The first-time pneumonia incidence rate was 71.67/1000 patient-years in high NLR group, which was markedly higher than that of 45.81/1000 patient-years in low NLR group. Kaplan–Meier curves indicated significant differences in the incidence of the first occurrence of pneumonia between two groups (log-rank test p = 0.015). The competitive risk model suggested a significant difference in the cumulative incidence of first pneumonia between the two groups (p = 0.032). Compared to low NLR group, adjusted Cox model showed that high NLR group was associated with increased risk of pneumonia incidence (HR, 1.51; 95% CI 1.04–2.21; p = 0.031). Forest plot showed no interaction was found in subgroups. The risk of pneumonia was significantly increasing in PD patients with high NLR, which may have a certain guiding significance for the clinic.

Tracing magnetically labeled cells with magnetic resonance imaging (MRI) is an emerging and promising approach to uncover in vivo behaviors of cells in cell therapy. Today, existing methods for the magnetic labeling of cells are cumbersome and time-consuming, which has greatly limited the progress of such studies on cell therapy. Thus, in this study, using the flow cytometric loading technology, we develop a sonoporation-based microfluidic chip (i.e., a microfluidic chip integrated with ultrasound; MCU), to achieve the safe, instant, convenient, and continuous magnetic labeling of cells. For the MCU we designed, a suitable group of operating conditions for safely and efficiently loading superparamagnetic iron oxide (SPIO) nanoparticles into DC2.4 cells was identified experimentally. Under the identified operating conditions, the DC2.4 cells could be labeled in approximately 2 min with high viability (94%) and a high labeling quantity of SPIO nanoparticles (19 pg of iron per cell). In addition, the proliferative functions of the cells were also well maintained after labeling. Furthermore, the in vivo imaging ability of the DC2.4 cells labeled using the MCU was verified by injecting the labeled cells into the leg muscle of the C57BL/6 mice. The results show that the excellent imaging outcome can be continuously achieved for 7 days at a density of 106 cells/mL. This work can provide insight for the design of magnetic cell labeling devices and promote the MRI-based study of cell therapies.

Hyperlipidemia is associated with chronic inflammation and intestinal dysbiosis. The purpose of this study was to investigate the protective effect of Nostoc sphaeroids Kütz (NO) on diet‐induced hyperlipidemia in mice. Experimental animals received a high‐fat diet (HFD) for 4 weeks, then an HFD supplemented with 2.5% or 7.5% NO for 6 weeks. HFD‐fed mice exhibited a significant increase in serum total cholesterol, triglycerides, and low‐density lipid cholesterol, and a decrease in high‐density lipid cholesterol. NO supplementation was associated with significantly lower dyslipidemia, decreased intestinal inflammation, and inhibition of toll‐like receptor 4 gene repression in HFD‐fed mice. Results suggest that NO treatment protected the integrity of the intestinal barrier. NO treatment was also associated with significant changes in the intestinal microbiota induced by HFD and an increase in the Firmicutes‐to‐Bacteroidetes ratio. Furthermore, NO treatment was also inversely correlated with mice obesity and hyperlipidemia NO and was associated with no significant in fecal short‐chain fatty acids. In conclusion, NO significantly ameliorated hyperlipidemia induced by a HFD in mice, potentially via a decrease intestinal inflammation, increase in intestinal barrier integrity, and amelioration in the gut microbiota., Nostoc sphaeroids Kütz ameliorates hyperlipidemia. Nostoc sphaeroids Kütz protects intestinal barrier. Nostoc sphaeroids Kütz ameliorates intestinal barrier.

Background A growing body of research suggests that major depressive disorder (MDD) is one of the most common psychiatric conditions associated with suicide ideation (SI). However, how a combination of easily accessible variables built a utility clinically model to estimate the probability of an individual patient with SI via machine learning is limited. Methods We used the electronic medical record database from a hospital located in western China. A total of 1916 Chinese patients with MDD were included. Easily accessible data (demographic, clinical, and biological variables) were collected at admission (on the first day of admission) and were used to distinguish SI with MDD from non-SI using a machine learning algorithm (neural network). Results The neural network algorithm distinguished 1356 out of 1916 patients translating into 70.08% accuracy (70.68% sensitivity and 67.09% specificity) and an area under the curve (AUC) of 0.76. The most relevant predictor variables in identifying SI from non-SI included free thyroxine (FT4), the total scores of Hamilton Depression Scale (HAMD), vocational status, and free triiodothyronine (FT3). Conclusion Risk for SI among patients with MDD can be identified at an individual subject level by integrating demographic, clinical, and biological variables as possible as early during hospitalization (at admission).

Hole transport layers (HTLs) play a vital role in organic solar cells (OSCs). In this work, a derivative of tetrathiafulvalene with four carboxyl groups TTA was introduced as a novel HTL to fabricate OSC with high performance. Displaying a better energy level match between HTL and active layers, the TTA based devices show a peak power conversion efficiency of 9.09%, which is comparable to the devices based on PEDOT:PSS. The favorable surface morphology recorded via atomic force microscopy, low series loss and charge recombination indicated by electrochemical impedance spectroscopy, synchronously verify the potential of TTA for application in OSCs as a valid kind of HTLs.

Objectives. The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention. Methods. In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model. Results. Of 1753 patients, the mean age was 51.1±14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29±1.75. During the follow-up period of 31.2±18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively (P<0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log rank=22.41, P<0.001). After adjusting for confounding factors, the highest MLR tertile was significantly associated with a hazard ratio (HR) for CVD mortality of 1.45 (95% confidence interval, 1.13-2.51, P=0.016). The Fine and Gray method analysis showed that using all-cause mortality as competing risk, the highest MLR tertile remained an independent predictor of CVD mortality (HR=1.39, 95% CI 1.10-2.47, P=0.021). Conclusions. Higher MLR levels at the commencement of PD may be independently associated with increased CVD mortality in PD patients.

The emerging threat of multi-drug resistance (MDR) in a wide range of diseases is a major public health problem, which prolongs treatment, imposes disabilities and reduces the expected life...

Over the past four decades, patients with advanced ovarian cancer (OC) has enjoyed greatly improved survival rate considering advances in combined chemotherapy with platinum and paclitaxel. We investigated the association between polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and short- and long-term efficacy of concurrent chemoradiotherapy (CCRT) in advanced OC. Patients with advanced OC and healthy females were selected in our study. Multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) were applied to detect homozygous deletions in GSTM1 and GSTT1, as well as codon 105 genetic polymorphisms in GSTP1 exon 5. All the patients with advanced OC were treated with CCRT. Toxicity of chemotherapy, short-term efficacy, recurrence and metastasis, respectively. Long-term survival outcomes were checked with a further examination and all patients were followed up for three years after CCRT.Compared with healthy females, patients with advanced OC showed higher frequencies of GSTT1 non-null genotype and homozygous mutation type GG of GSTP. GSTP1genetic polymorphisms were relevant to neutropenia resulted from CCRT in patients with advanced OC. Compared with patients with GSTT1non-null genotype, those with GSTT1 null genotype appeared to enjoy a better short-term efficacy, lower recurrence and metastasis rate, higher survival rate and longer mean survival time. Compared with patients with GG genotype, those with GSTP1 AA + AG genotype also enjoyed more positive results. Our results reveal that GSTT1 null genotype and GSTP1AA + AG genotype are associated with short- and long-term efficacy of CCRT in advanced OC.

Autophagy allows cancer cells to respond changes in nutrient status by degrading and recycling non-essential intracellular contents. Inhibition of autophagy combined with nutrient deprivation is an effective strategy to treat cancer. Pain is a primary determinant of poor quality of life in advanced cancer patients, but there is currently no satisfactory treatment. In addition, effective treatment of cancer does not efficiently relieve cancer pain, but may increase pain in many cases. Hence, few studies focus on simultaneous cancer therapy and pain relief, and made this situation even worse. Method: Ropivacaine was loaded into tumor-active targeted liposomes. The cytotoxicity of ropivacaine-based combination therapy in B16 and HeLa cells were tested. Moreover, a mice model of cancer pain which was induced by inoculation of melanoma near the sciatic nerve was constructed to assess the cancer suppression and pain relief effects of ropivacaine-based combination therapy. Results: Ropivacaine and ropivacaine-loaded liposomes (Rop-DPRL) were novelly found to damage autophagic degradation. Replicated administration of Rop-DPRL and calorie restriction (CR) could efficiently repress the development of tumor. In addition, administration of Rop-DPRL could relieve cancer pain with its own analgestic ability in a short duration, while repeated administration of Rop-DPRL and CR resulted in continuous alleviation of cancer pain through reduction of VEGF-A levels in advanced cancer mice. Further, dual inhibition of phosphorylation of STAT3 at Tyr705 and Ser727 by Rop-DPRL and CR contribute to the reduction of VEGF-A. Conclusion: Combination therapy with Rop-DPRL and nutrient deprivation simultaneously suppresses cancer growth and relieves cancer pain.

This study focuses on adopting Battery Performance and Cost model (BatPaC) to provide a comprehensive design of a high capacity lithium ion battery (LIB) pack with a silicon nanowire (SiNW) anode and a lithium nickel manganese cobalt oxide (LiNi1/3Mn1/3Co1/3O2, NMC) cathode for next-generation (NG) LIB technologies for electric vehicle (EV) applications. The battery pack is denoted as NMC-SiNW and configured to have a power output of 120 kW for powering an EV under the requirement of 320 km driving distance per charge. Three interconnected models--vehicle model, battery kinetic model, and battery configuration model--are adopted for the configuration of the NMC-SiNW battery pack. Then the cost modeling of the battery pack is developed. The configuration and cost results of the NMC-SiNW battery pack is then benchmarked with those of a conventional NMC-Graphite battery pack. It is found that compared with the NMC-Graphite battery pack, the NMC-SiNW battery pack has advantages of lighter weight (335 kg vs. 418 kg), higher energy density (190 Wh kg-1 vs. 152 Wh kg-1), lower total battery cost to the OEM ($10132 vs. $10702), and lower specific energy cost (160 $/kWh vs. 169 $/kWh). This study provides insights into the design of high capacity LIB technologies with nanostructured Si anode materials, demonstrates their advantages in advancing both technical and economic performances of LIB technologies, and thus indicates their promise for future large-scale applications in EVs.

Background Hypercholesterolemia is a disease associated with numerous health problems. Growing evidence indicates that hypercholesterolemia, hyperlipidemia is closely linked to chronic inflammation, which can lead to cardiovascular disease, fatty liver disease, and type 2 diabetes. Objective The purpose of this study was to investigate the protective effect of Nostoc sphaeroids Kutz (NO) on diet-induced hyperlipidemia in mice. Design At first, experimental animals received a high-fat diet (HFD) for 4 weeks, and then received a HFD supplemented with 2.5% or 7.5% NO for 6 weeks. In the current study, results show that treatment with NO decreases weight gain and liver index induced by HFD. In addition, the serum levels of TC, TG and LDL are significantly decreased in NO treatment groups. Results From the results of Oil Red staining and Hematoxylin and eosin staining (HE), treatment with NO significantly reduces liver lipid accumulation and protect liver structure. Further analysis reveals that NO has positive effects on liver lipid metabolism and inflammation, as showed by the lower protein expressions of FAS and SREBP-1, the lower concentrations of TNF-α, IL-1β, IL-6, and the lower gene expressions of TNF-α, IL-1β, IL-6 and NF-kB. Conclusions Our results indicate that NO may significantly ameliorate diet-induced hyperlipidemia, which is possibly associated with improving liver lipid metabolism and reducing chronic inflammation.

A series of economic, social and political issues have arisen with the aggravation of environmental issues. The public's higher expectations and requirements for environmental quality urge the reform for the most stringent environmental management system, which expedites the environmental tax reform. Pollutant discharge fee (PDF) is the earliest economic means adopted for environmental purpose in China. It has made important contributions to the cause of environmental protection by encouraging businesses to strengthen environmental management and reduce pollutant emissions, and raising environmental protection funds. However, some problems were revealed in the actual implementation process, such as insufficient enforcement rigidity, intervention of local governments and departments, and negotiated payment. On January 1, 2018, China launched the environmental protection tax (EPT) policy, which was China's first green tax aimed at environmental protection, putting an end to PDF that had been in effect for the past 40 years. The policy sets different pollutant equivalent values (PEVs) for pollution factors with different levels of hazard to tax high-hazard pollution factors more heavily. This regulates corporate behavior of pollutant discharge and encourages businesses to reduce pollutant emissions. By mean of rigid taxation, the policy gives full play to its regulatory functions. Overall, the EPT policy has been smoothly implemented for over one year, with some problems encountered in the process. The paper will evaluate the policy impacts in the first year, summarize experiences and identify problems in a timely manner, and propose measures to optimize the policy design and recommendations on tax collection and management, in the hope of facilitating further reform and innovation of China's environmental tax policy.

Objectives: Our objective was to present the experience on prenatal diagnosis of 1p36 terminal deletion, and further delineated the fetal presentation of the syndrome. Material and methods : This was a retrospective analysis of three new prenatal cases with pure 1p36 terminal deletion detected by chromosome microarray analysis (CMA) at a single Chinese medical center. We also reviewed 11 published prenatal cases with similar deletion sizes. Clinical data of all cases including indications for invasive testing, sonographic findings, maternal factors, and pregnancy outcomes were reviewed and analyzed. Results: Three new cases with pure 1p36 terminal deletion were prenatal diagnosed by CMA, the sizes of the deletion were 1.3 Mb, 5.0 Mb, and 4.9 Mb respectively. All cases were detected because of abnormal ultrasound findings, including central nervous system (CNS) abnormalities, congenital heart disease (CHD) and fetal growth restriction. Two pregnancies were terminated, and one was live-born but died three months after birth. Conclusions: The 1p36 terminal deletion results in many clinical manifestations, but the specificity of clinical features are not high. Prenatal sonographic findings such as CNS, CHD may act as suggestive signs of 1p36 deletion or other microdeletion/duplication syndromes.

High-fat (HF) diet-induced neuroinflammation and cognitive decline in humans and animals have been associated with microbiota dysbiosis via the gut-brain axis. Our previous studies revealed that excretory-secretory products (ESPs) derived from the larval Echinococcus granulosus (E. granulosus) function as immunomodulators to reduce the inflammatory response, while the parasitic infection alleviates metabolic disorders in the host. However, whether ESPs can improve cognitive impairment under obese conditions remain unknown. This study aimed to investigate the effects of E. granulosus-derived ESPs on cognitive function and the microbiota-gut-brain axis in obese mice. We demonstrated that ESPs supplementation prevented HF diet-induced cognitive impairment, which was assessed behaviorally by nest building, object location, novel object recognition, temporal order memory, and Y-maze memory tests. In the hippocampus (HIP) and prefrontal cortex (PFC), ESPs suppressed neuroinflammation and HF diet-induced activation of the microglia and astrocytes. Moreover, ESPs supplementation improved the synaptic ultrastructural impairments and increased both pre- and postsynaptic protein levels in the HIP and PFC compared to the HF diet-treated group. In the colon, ESPs reversed the HF diet-induced gut barrier dysfunction, increased the thickness of colonic mucus, upregulated the expression of zonula occludens-1 (ZO-1), attenuated the translocation of bacterial endotoxins, and decreased the colon inflammation. Notably, ESPs supplementation alleviated the HF diet-induced microbiota dysbiosis. After clarifying the role of antibiotics in obese mice, we found that broad-spectrum antibiotic intervention abrogated the effects of ESPs on improving the gut microbiota dysbiosis and cognitive decline. Overall, the present study revealed for the first time that the parasite-derived ESPs alleviate gut microbiota dysbiosis and improve cognitive impairment induced by a high-fat diet. This finding suggests that parasite-derived molecules may be used to explore novel drug candidates against obesity-associated neurodegenerative diseases.

PurposeThis study aims to validate the value of microRNA (miRNA) detection for triaging human papillomavirus (HPV)-positive women in the general population.Patients and MethodsmiR-375 detection in cervical exfoliated cells has been demonstrated to have the superior value to cytology in triaging primary HPV-positive women in the hospital population. In this study, residual samples of cervical exfoliated cells from 10,951 women in a general population were used to detect miRNA. The performance efficiency of miRNA detection in identifying high-grade cervical intraepithelial neoplasia (CIN) was evaluated. Pearson chi-square test and McNemar pairing test were used to compare miRNA detection and cytology.ResultsIn valid 9,972 women aged 25–65, miR-375 expression showed a downward trend along with an increase in cervical lesion severity. The expression level of miR-375 ≤1.0 × 10-3 was identified as positive. In the HPV-positive and 12 HPV genotypes other than 16/18 (HR12)-positive women, miR-375 detection showed equivalent sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to that of cytology (≥ASC-US) and higher or similar sensitivity and NPV but lower specificity and PPV than that of cytology (≥ASC-H) in identifying CIN3+ and CIN2+. In HPV 16-positive women, miR-375 positivity had higher sensitivity and NPV but lower specificity and PPV than that of cytology (≥ASC-H and HSIL) in identifying CIN3+ and CIN2+. The immediate CIN3+ risk of miR-375 positivity was 19.8% (61/308) in HPV-positive, 10.8% (22/204) in HR12-positive, and 43.5% (37/85) in HPV16-positive women, respectively.ConclusionThe detection of miR-375 in cervical exfoliated cells may be an optional method for triaging primary HPV-positive women in population-based cervical cancer screening.

Wafer direct bonding is an attractive approach to manufacture future micro-electro-mechanical system (MEMS) and microelectronic and optoelectronic devices. In this paper, a combined hydrophilic activated Si/Si wafer direct bonding process based on wet chemical activation and O2 plasma activation is explored. Additionally, the effect on bonding interface characteristics is comprehensively investigated. The mechanism is proposed to better understand the nature of hydrophilic bonding. The water molecule management is controlled by O2 plasma activation process. According to the contact angle measurement and FTIR spectrum analysis, it can be concluded that water molecules play an important role in the type and density of chemical bonds at the bonding interface, which influence both bonding strength and voids’ characteristics. When annealed at 350 °C, a high bonding strength of more than 18.58 MPa is obtained by tensile pulling test. Cross sectional SEM and TEM images show a defect-free and tightly bonded interface with an amorphous SiOx layer of 3.58 nm. This amorphous SiOx layer will induce an additional energy state, resulting in a lager resistance. These results can facilitate a better understanding of low-temperature hydrophilicity wafer direct bonding and provide possible guidance for achieving good performance of homogenous and heterogenous wafer direct bonding.

The sparse principal component analysis (SPCA) is widely used in the fault detection for nonlinear complex chemical processes in recent years. However, insufficient data processing, fixed models and fault type single classification cannot be used in the time-varying process. Therefore, a novel adaptive sparse principal component analysis (ASPCA) algorithm fused with improved variation mode decomposition (IVMD) (ASPCA-IVMD) is proposed for fault detection in chemical processes. The bat algorithm is innovatively integrated to optimize the parameters of the variable modulus decomposition. Then the optimized parameters are used for data preprocessing to suppress noise. In addition, based on the traditional SPCA, the threshold calculation is fused to realize the adaptive selection of principal components. After the principal components are determined, T2 and Q statistics are used for fault detection. Finally, the proposed method is verified by the Tennessee Eastman process case. The results demonstrate that the proposed method can select the principal components adaptively according to the data for having the real-time property of chemical process. Meanwhile, compared with traditional methods (principal component analysis, sparse principal component analysis, deep belief network integrating dropout, adaptive unscented Kalman filter integrating radial basis function and sparse deep belief network), the detection rate of the ASPCA-IVMD method is more than 99%, which shows superiority.

Undoubtedly, opioid drugs have been the most popular treatment for refractory pain since found, such as morphine. However, tolerance to the analgesic effects caused by repeated use is inevitable, which greatly limits the clinical application of these drugs. Nowadays, it has become the focus of the world that further development of non-opioid-based treatment along with efficient strategies to circumvent opioid tolerance are urgently needed clinically. Fortunately, electro-acupuncture (EA) provides an alternative to pharmaceutic treatment, remaining its potential mechanisms unclear although. This study was aimed to observe the effects of EA on morphine-induced tolerance in mice and discover its underlying mechanism. Tail-flick assay and hot-plate test were conducted to assess the development of tolerance to morphine-induced analgesia effect. As a result of repeated administration scheme (10 mg/kg, twice per day, for 7 days), approximately a two-fold increase was observed in the effective dose of 50% (ED50) of morphine-induced antinociceptive effect. Interestingly, by EA treatment (2/100Hz, 0.5, 1.0, and 1.5 mA, 30 min/day for 7 days) at the acupoints Zusanli (ST36) and Sanyinjiao (SP6), morphine ED50 curves was remarkably leftward shifted on day 8. In addition, the RNA sequencing strategy was used to reveal the potential mechanisms. Due to the well described relevance of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), extracellular regulated protein kinases (ERK), and cAMP response element-binding (CREB) in brainstem (BS) to analgesia tolerance, the cAMP-PKA/ERK-CREB signaling was deeply concerned in this study. Based upon Enzyme-Linked Immunosorbent Assay, the up-regulation of the cAMP level was observed, whereas reversed with EA treatment. Similarly, western blot revealed the phosphorylation levels of PKA, ERK, and CREB were up-regulated in morphine tolerant mice, whereas the EA group showed a significantly reduced expression level instead. This study observed an attenuating effect of the EA at ST36 and SP6 on morphine tolerance in mice, and suggested several potential biological targets by RNA-seq, which include the cAMP-PKA/ERK-CREB signaling pathway, strongly supporting a useful treatment for combatting the opioid epidemic, and opioid-tolerant patients.

Direct polarization using a single pulse is the simplest excitation scheme in nuclear magnetic resonance (NMR) experiments, capable of quantifying various compositions in many materials applications. However, this single-pulse excitation generally gives rise to NMR spectra with a severely distorted baseline due to the background signals arising from probe components and/or due to the radio-frequency (RF) acoustic ringing, especially in low-γ nuclei and wide-line NMR. In this work, a triple-pulse excitation scheme is proposed to simultaneously suppress the background signals and eliminate the RF acoustic ringing. The acoustic ringing is cancelled through subtraction in any two consecutive scans by alternating the receiver phase while keeping the phase of the pulse right before acquisition the same. While the triple-pulse scheme generates an additional flip-angle dependent scaling to the traditional single-pulse excitation profile in such a way that the scaling is one when the flip-angle is ∼90° but becomes almost zero when the flip-angle is very small. Therefore, the background signals arising from the materials outside the sample coil experiencing a very small fraction of the RF flip-angles can be effectively suppressed. Various samples containing 1H and quadrupolar nuclei (17O, 25Mg, and 23Na) have been used to demonstrate the effectiveness of this newly proposed triple-pulse excitation in terms of suppressing the background signals and eliminating the acoustic ringing effects.