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Background: Postoperative outcome following deep brain stimulation (DBS) of the subthalamic nucleus is variable, particularly with respect to axial motor improvement. We hypothesized a genetic underpinning to the response to surgical intervention, termed “surgicogenomics”. Objective: We aimed to identify genetic variants associated with clinical heterogeneity in DBS outcome of Parkinson’s disease (PD) patients that could then be applied clinically to target selection leading to improved surgical outcome. Methods: Retrospective clinical data was extracted from 150 patient’s charts. Each individual was genotyped using the genome-wide NeuroX array tailored to study neurologic diseases. Genetic data were clustered based on surgical outcome assessed by comparing pre- and post-operative scores of levodopa equivalent daily dose and axial impairment at one and five years post-surgery. Allele frequencies were compared between patients with excellent vs. moderate/poor outcomes grouped using a priori defined cut-offs. We analyzed common variants, burden of rare coding variants, and PD polygenic risk score. Results: NeuroX identified 2,917 polymorphic markers at 113 genes mapped to known PD loci. The gene-burden analyses of 202 rare nonsynonymous variants suggested a nominal association of axial impairment with 14 genes (most consistent with CRHR1, IP6K2, and PRSS3). The strongest association with surgical outcome was detected between a reduction in levodopa equivalent daily dose and common variations tagging two linkage disequilibrium blocks with SH3GL2. Conclusion: Once validated in independent populations, our findings may be implemented to improve patient selection for DBS in PD.

Graft-versus-host disease (GVHD) is an important complication after allogeneic haematopoietic stem cell transplantation (HSCT). Corticosteroids are the standard first-line treatment. Steroid-resistant/-dependent (SR/D) acute and chronic GVHD (aGVHD, cGVHD) lead to significant morbidity/mortality. The JAK2 inhibitor ruxolitinib has recently been shown in clinical trials to be effective in SR/D aGVHD and cGVHD. We retrospectively analysed the efficacy and safety of ruxolitinib in a cohort of SR/D aGVHD and cGVHD patients treated in a non-trial setting. In the aGVHD cohort, there were 14 men and 12 women, median age at 38 (19–63) years. At day 28 post-ruxolitinib, the overall response rate (ORR) was 86% (complete response, CR, 36%; partial response, PR, 50%). Continued ruxolitinib beyond day 28 resulted in a final CR of 68%. However, 3/15 (20%) of CR patients developed cGVHD. In the cGVHD cohort, there were 16 men and 15 women, median age at 33 (21–64) years. The ORR, CR and PR rates changed with continued ruxolitinib treatment, being 86%, 17% and 69% at 1 month; 79%, 38% and 41% at 3 months; and 83%, 52% and 31% at 6 months. Five patients had overlap GVHD, four of whom achieved CR. Multivariate analysis showed that superior overall survival and failure-free survival were associated with CR at day 28 for aGVHD, and CR at 1 year for cGVHD. Ruxolitinib treatment was efficacious for SR/D aGVHD and cGVHD, and continued treatment for at least 6 months was needed to maximize benefit.

BackgroundMKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC).MethodsOncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan–Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene–miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database.ResultsMKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways.ConclusionMKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.

Background Sex determining region Y-box 2 (SOX2) has been reported as a potential therapeutic target for cancer. However, the role of SOX2 in cervical cancer remains largely undetermined. This study was performed to evaluate the correlation of SOX2 with clinical characteristics and prognosis in cervical cancer. Methods Multiple databases were systematically searched for eligible publications. The combined odds ratios (ORs) or hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were used to assess the effect sizes. Results A total of 17 studies with 1906 participants were identified. SOX2 expression was higher in cervical cancer than in the normal control group (OR = 10.83, 95% CI = 6.64–17.67, P < 0.001), while no significant difference was observed between cervical cancer and cervical intraepithelial neoplasia. SOX2 expression was not associated with age, tumor stage, and lymph node metastasis, but was correlated with tumor grade (grade 2–3 vs. grade 1: OR = 4.59, 95% CI = 2.76–7.62, P < 0.001) and tumor size (≥4 cm vs. ≤4 cm: OR = 1.66, 95% CI = 1.05–2.60, P = 0.028). Based on multivariate Cox analysis, SOX2 expression was not correlated with overall survival, but was closely associated with poor recurrence-free survival (HR = 5.83, 95% CI = 1.35–25.16, P = 0.018) and progress-free survival HR = 2.29, 95% CI = 1.01–5.19, P = 0.046). Conclusion SOX2 may serve as a novel prognostic factor and a promising molecular target for cervical cancer.

Yu-Yan Wu,&ast; Yong Tan,&ast; Min Yan, Zhen Cheng, Xiang-Tao Pan Department of Hematology, Taicang Hospital of Soochow University, Taicang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang-Tao PanDepartment of Hematology, Taicang Hospital of Soochow University, No. 58. of South Changsheng Road, Taicang, Jiangsu, People’s Republic of ChinaTel +86 18915768003Email Panxt99xt@email.cnObjective: To investigate the characteristics of coagulation indicators, such as C-reactive protein (CRP), antithrombin (AT), and fibrinogen (FB) in patients with pulmonary thromboembolism (PTE) and their relationship with PTE.Methods: The clinical characteristics, CRP, AT, FB, plasma D-dimer (D-D) and platelet (PLT) counts, and blood coagulation indicators of 433 patients with PTE diagnosed by computed tomographic pulmonary angiography (CTPA) were comprehensively analyzed, and the relevant clinical significance was discussed.Results: The total incidence of PTE was 1.60% (433/270,983 cases), and the age group with the highest incidence was over 60 years old. D-D increased in 412 (95.2%) patients. PLT was normal in 331 (76.4%) cases, but decreased in 53 (12.3%) cases and increased in 49 (11.3%) cases. CRP increased in 76.0% (288/379 cases) and was normal in 24.0% (91/379 cases). AT decreased in 109 (25.2%) cases and FB increased in 102 (23.6%) cases. There were no significant changes in other coagulation indexes. CRP was positively correlated with PLT and FB (r = 0.1026, t = 2.0118, P < 0.05, and r = 0.5360, t = 12.2963, P < 0.01, respectively). CRP was negatively correlated with AT (r = – 0.2005, t = 4.0100, P < 0.01).Conclusion: The incidence of PTE was higher in hospitalized patients. Most patients with PTE have increased CRP and FB and decreased AT, and these levels may be related to the occurrence of PTE.Keywords: pulmonary thromboembolism, C-reactive protein, antithrombin, fibrinogen, D-dimer, platelets

Despite several recent advances, current therapy and prevention strategies for myocardial infarction are far from satisfactory, owing to limitations in their applicability and treatment effects. Nanoparticles (NPs) enable the targeted and stable delivery of therapeutic compounds, enhance tissue engineering processes, and regulate the behaviour of transplants such as stem cells. Thus, NPs may be more effective than other mechanisms, and may minimize potential adverse effects. This review provides evidence for the view that function-oriented systems are more practical than traditional material-based systems; it also summarizes the latest advances in NP-based strategies for the treatment and prevention of myocardial infarction.

This paper investigates decentralized composite optimization problems involving a common non-smooth regularization term over an undirected and connected network. In the same situation, there exist lots of gradient-based proximal distributed methods, but most of them are only sublinearly convergent. The proof of linear convergence for this series of algorithms is extremely difficult. To set up the problem, we presume all networked agents use the same non-smooth regularization term, which is the circumstance for most machine learning to implement based on centralized optimization. For this scenario, most existing proximal-gradient algorithms trend to ignore the cost of gradient evaluations, which results in degraded performance. To tackle this problem, we further set the local cost function to the average of a moderate amount of local cost subfunctions and develop an edge-based stochastic proximal gradient algorithm (SPG-Edge) by employing local unbiased stochastic averaging gradient method. When the non-smooth term does not exist, the proposed algorithm could be extended to some notable primal-dual domain algorithms, such as EXTRA and DIGing. Finally, we provide a simplified proof of linear convergence and conduct numerical experiments to illustrate the validity of theoretical results.

The pulsatile stress in the microcirculation may contribute to development or progression of chronic kidney disease. However, there is no prospective data confirming whether pulsatile stress in early life affect renal function in middle age. The authors performed a longitudinal analysis of 1738 participants aged 6–15 years at baseline, an ongoing Adolescent Prospective Cohort with a follow‐up of 30 years. The authors evaluated the association between pulsatile stress in childhood and adult subclinical renal damage (SRD), adjusting for related covariates. Pulsatile stress was calculated as resting heart rate × pulse pressure. Renal function was assessed with estimated glomerular filtration rate (eGFR) and urine albumin‐to‐creatinine ratio (uACR). The results showed that pulsatile stress in childhood was associated with adult SRD (Relative Risk, 1.43; p = .032), and the predictive value of combined pulse pressure and heart rate for SRD was higher than either of them alone. The high pulsatile stress in childhood increased the risk of adult SRD in males (RR, 1.92; p = .003), but this association was not found in females (RR, 0.91; p = .729). Further, the participants were categorized into four groups on the basis of pulsatile stress status in childhood and adulthood. Male patients with high pulsatile stress during childhood but normal pulsatile stress as adults still had an increased risk of SRD (RR, 2.04; 95% CI, 1.18–3.54), while female patients did not (RR, 0.96; 95% CI, 0.46–1.99). The study demonstrated that high pulsatile stress in childhood significantly increased the risk of adult SRD, especially in males. Adequate control of pulse pressure and heart rate from childhood, in the long‐term, is very important for preventing kidney damage.

Rapid investment casting based on additive manufacturing has been widely used because of rapid production of patterns without any tooling requirements. However, the precision wax patterns fabricated by commercial additive manufacturing machine directly is costly. The main objective of this study is to demonstrate a cost-efficient approach for low-volume production of wax patterns by integration of rapid tooling technology, low-pressure wax injection molding, and 3D optical inspection technologies. A dimensional compensation method was used to compensate dimensional changes in the manufacturing process of precision wax pattern. Finally, a case study was examined to illustrate the effectiveness of the proposed method. It was found that the radial and axial shrinkage of the entire manufacturing process are approximately 1.75% and 3.34%, respectively. A simple empirical formula that the dimensions of radial and axial in the design layout are compensated by approximately 0.75 mm and 1 mm when the wax pattern dimension is within 10 mm to 45 mm was proposed. The total production cost of fabricating twenty wax patterns by the proposed method in this study can be saved by about 86% compared to that of fabricating twenty wax patterns by commercial additive manufacturing machine directly. The remarkable findings in this study are very practical and provide the greatest application potential for the fabrication of precision wax pattern economically and efficiently in the investment casting industry.

In electronic bipolar resistive switching (eBRS), the electron trapping and detrapping at the defect sites within the switching layer, such as the highly defective TiO1.7 in this study, constitute the switching mechanism. It is an appealing candidate solution to the nonuniformity issue of resistive switching memory. However, TiO1.7-based eBRS has suffered from a lack of endurance and retention. In this study, a 7 nm-thick stoichiometric TiO2 layer is interposed between an Al bottom electrode and a 50 nm-thick TiO1.7 layer, which is in contact with an Al top electrode. Despite the minimal structural modification, improvements in the electrical performance were substantial. The off-to-on state resistance ratio of 20 and the resistance values could be retained up to 30 000 direct current sweep cycles and 106 alternating current pulse switching cycles. Data retention also significantly improves. Moreover, the device is electroforming-free and shows fully area-type switching characteristics. Such notable improvements are attributed to the favorable energy band structure of the Al/TiO1.7/TiO2/Al structure. The device shows almost linear potentiation and depression characteristics after the repeated pulse voltage applications, which significantly improves the accuracy of the neural network, the synapses of which are composed of the Al/TiO1.7/TiO2/Al memory cells.

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low‐salt diet (3.0 g) for 7 days, and a high‐salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt‐Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high‐salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high‐salt diet than on a low‐salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high‐salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low‐salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.

Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression. To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process. We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively. Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST. Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.

Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.

Aiming at the local fault diagnosis of planetary gearbox gears, a feature extraction method based on improved dynamic time warping (IDTW) is proposed. As a calibration matching algorithm, the dynamic time warping method can detect the differences between a set of time-domain signals. This paper applies the method to fault diagnosis. The method is simpler and more intuitive than feature extraction methods in the frequency domain and the time-frequency domain, avoiding their limitations and disadvantages. Due to the shortcomings of complex calculation, singularity and poor robustness, the paper proposes an improved method. Finally, the method is verified by envelope spectral feature analysis and the local fault diagnosis of gears is realised.

Aims Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. Method and results MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and type 2 innate lymphoid cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. Conclusion IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Translational perspective Accumulating evidence suggests that modulation of innate and adaptive immune responses is a promising therapeutic strategy for myocardial infarction. In this study, we demonstrate that IL-5 exerts cardioprotective effects on infarcted myocardium by promoting eosinophil accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Hence, regulation of cardiac IL-5 level or eosinophil count may become a therapeutic approach for post-myocardial infarction cardiac repair in humans.

Freezing of gait (FOG) is considered one of the most disturbing and least understood symptoms in Parkinson’s disease (PD). The reported prevalence rates of FOG in PD vary widely, ranging from 5 to 85.9%. We conducted a systematic review and meta-analysis to provide a reliable estimate of the average point prevalence of FOG in PD, and we further investigated the study characteristics that might have influenced the estimate. We searched different databases to identify studies that report the prevalence of FOG in PD or include relevant raw data for further calculation. The last inclusion date was February 20, 2020. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used for the quality assessment, and articles that met the predefined criteria were included in the quantitative analysis. Sixty-six studies were selected from 3392 references. A weighted prevalence of 50.6% in 9072 PD patients experienced FOG based on the special questionnaires (the FOG-Q and NFOG-Q), which was about twice as high as that assessed by the specific items of the clinical rating scales (UPDRS item2.14 and MDS-UPDRS item3.11) (23.2%) or simple clinical questions (25.4%). The weighted prevalence was 37.9% for early stage (≤ 5 years) and 64.6% for advanced stage (≥ 9 years). Moreover, a higher prevalence was calculated from the population-based studies than that in multicenter and single-center studies (47.3% vs. 33.5% and 37.1%, respectively). The result from this systematic review confirms that FOG is very common in PD and its prevalence is usually underestimated in hospital settings. Importantly, a more accurate assessment of FOG in future clinical researches would involve the use of special FOG scale rather than a single item on a scale or a general clinical inquiry.

Kai Yuan,1,2 Jin Long Zhang,2 Jie Yu Yan,2 Bing Yuan,1 Jin Xin Fu,2 Yan Wang,2 Xue Dong Sun,3 Yang Guan,2 Feng Duan,2 Mao Qiang Wang1,2 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Department of Interventional Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of ChinaCorrespondence: Mao Qiang WangDepartment of Interventional Radiology, The Fifth Medical Center, Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing, 100853, People’s Republic of ChinaTel +86 10-66937190Email wangmq@vip.sina.comPurpose: To assess the long-term outcome of performing uterine artery embolization (UAE) using small particles in women with symptomatic adenomyosis (AD).Methods: Twenty-seven consecutive women (median age 42 years, range 29– 53 years) with AD, in eight cases AD combined with fibroids, who underwent UAE between February 2015 and January 2019, were retrospectively analyzed. The embolization was performed using small-sized polyvinyl alcohol particles (100 μm and 300 μm). The patients completed the Uterine Fibroid Symptom and Quality of Life questionnaire at baseline and at a 42-month follow-up (range 24– 71). The junction zone (JZ) thickness and uterine volume were also calculated at baseline and at a three-month follow-up.Results: The total symptom severity score (SSS) decreased from a median of 59 (range 34– 78) at baseline to a median of 9 (range 3– 47) at the end of this study; the health-related quality of life score (HRQOL) increased from a median of 38 (range 23– 49) at baseline to a median of 84 (range 46– 97) at 42 months. Twenty of the 27 patients were asymptomatic. The clinical response of the remaining seven women was little improvement in their symptoms, and one of the seven women underwent a hysterectomy at 35 months. Twenty-six of the 27 (96%) patients had a preserved uterus at the 42-month follow-up. There was no difference after UAE in SSS, HRQOL, junction zone (JZ) thickness, and uterus volume between patients with pure AD and those with AD combined with fibroids (p = 0.729, 0.710, 0.973, and > 0.99). There was no difference in the JZ thickness and uterus volume at baseline between the asymptomatic women and the women with an insufficient response (p = 0.854 and 0.253), and there were no major complications afterwards.Conclusion: From the long-term follow-ups, it could be seen that UAE using small particles is safe and effective in treating AD, especially in preserving the uterus. There is no relationship between the clinical outcomes and the initial presence of AD, with or without fibroids, and the JZ thickness at baseline does not seem to be a predictor for the long-term outcome of UAE.Keywords: adenomyosis, uterine artery embolization, UFS–QoL, interventional radiology

In this paper, we present an experimental study in which an electroencephalogram (EEG) device was used to measure cognitive load in programmers as they attempted to predict the output of C code sni...

With the development of big data technology, the data management of complex applications has become more and more resource intensive. In this paper, we propose an automatic approach (DRLISA) to achieve NoSQL database index selection. For different workloads, we automatically select its corresponding indexes and parameters which can totally improve the database performance. Our DRLISA establishes an optimal index by building a deep reinforcement learning model which is able to adapt the dynamic change of workloads. We conducted our experiments in five aspects (the impact of data manipulation, the impact of operation count, comparison with random selection, comparison with existing method and the robustness of DRLISA) using the open source benchmark, YCSB. The experimental results showed that DRLISA has a high efficient index recommendation under the dynamic workloads.

Carbon fiber reinforced polymer confined concrete-filled steel tube (CFRP-CFST) columns are having promising utilization in offshore structures, which are usually subjected to the combination of axial forces, bending moments, and torsional moments. This paper thus presents a finite element (FE) study on CFRP-CFST columns under combined compression-bending-torsion load. The comprehensive FE modelling was established and then validated by the experimental data. Analysis of typical failure modes, load-deformation relations and full-range behavior was performed based on the FE simulation. Meanwhile, parametric analysis was conducted to reveal the sensitive parameters as well as their influence on the structural behavior and ultimate capacity of CFRP-CFST columns. Finally, correlation relations which can reasonably characterize the coupled ultimate capacity of columns were obtained and validated. Correspondingly, simplified design formulae for predicting the ultimate capacity correlation of CFRP-CFST columns under compression-bending-torsion load were proposed.

Background: The host innate immune system can recognize Pathogen-Associated Molecular Patterns (PAMPs) through Pattern Recognition Receptors (PRRs), thereby initiating innate immune responses and subsequent adaptive immune responses. PAMPs can be developed as a vaccine adjuvant for modulating and optimizing antigen-specific immune responses, especially in combating viral infections and tumor therapy. Although several PAMP adjuvants have been successfully developed they are still lacking in general, and many of them are in the preclinical exploration stage. Objective: This review summarizes the research progress and development direction of PAMP adjuvants, focusing on their immune mechanisms and clinical applications. Methods: PubMed, Scopus, and Google Scholar were screened for this information. We highlight the immune mechanisms and clinical applications of PAMP adjuvants. Results: Because of the differences in receptor positions, specific immune cells targets, and signaling pathways, the detailed molecular mechanism and pharmacokinetic properties of one agonist cannot be fully generalized to another agonist, and each PAMP should be studied separately. In addition, combination therapy and effective integration of different adjuvants can increase the additional efficacy of innate and adaptive immune responses. Conclusion: The mechanisms by which PAMPs exert adjuvant functions are diverse. With continuous discovery in the future, constant adjustments should be made to build new understandings. At present, the goal of therapeutic vaccination is to induce T cells that can specifically recognize and eliminate tumor cells and establish long-term immune memory. Following immune checkpoint modulation therapy, cancer treatment vaccines may be an option worthy of clinical testing.

Background and purpose. A single nucleotide polymorphism at nucleotide 196 (G/A) in the human brain-derived neurotrophic factor ( BDNF) gene produces an amino acid substitution (valine to methionine) at codon 66(Val66Met). It is unclear whether carriers of this substitution may have worse functional outcomes after stroke. We aimed to explore the distribution of Val66Met polymorphism and evaluate the effect of different genotypes on stroke functional recovery. Methods. Several databases were searched using the keywords BDNF or brain-derived neurotrophic factor, codon66, G196A, rs6265, or Val66Met, and stroke. Results. A total of 25 articles were relevant to estimate the distribution of alleles; 5 reports were applied in the meta-analysis to assess genetic differences on recovery outcomes. The genetic model analysis showed that the recessive model should be used; we combined data for AA versus GA+GG (GG—Val/Val, GA—Val/Met, AA—Met/Met). The results showed that stroke patients with AA might have worse recovery outcomes than those with GA+GG (odds ratio = 1.90; 95% CI: 1.17-3.10; P = .010; I2 = 69.2%). Overall, the A allele may be more common in Asian patients (48.6%; 95% CI: 45.8%-51.4%, I2 = 54.2%) than Caucasian patients (29.8%; 95% CI: 7.5%-52.1%; I2 = 99.1%). However, in Caucasian patients, the frequency of the A allele in Iranians (87.9%; 95% CI: 83.4%-92.3%) was quite higher than that in other Caucasians (18.7%; 95% CI: 16.6%-20.9%; I2 = 0.00%). Conclusion. Val66Met AA carriers may have worse rehabilitation outcomes than GA+GG carriers. Further studies are needed to determine the effect of Val66Met polymorphism on stroke recovery and to evaluate this relationship with ethnicity, sex, age, stroke type, observe duration, stroke severity, injury location, and therapies.

AIM: To compare the outcomes between early surgery and late surgery for intermittent exotropia (IXT) with a Meta-analysis. METHODS: Scientific databases including PubMed, Embase, Web of Science, Cochrane and China National Knowledge Infrastructure were searched prior to December 16, 2019. From this broad database search, we performed some Meta-analysis including eleven independent studies, to further evaluate the outcome(s) when comparing early versus late surgery for IXT. The boundaries between early and late surgery and the surgery methods were not inconsistent, so subgroup analyses were conducted by different boundaries of age at surgery and different surgical approaches. The pooled odds ratios (ORs) and the 95% confidence interval (CI) were estimated according to the random-effects model for high heterogeneity between studies. RESULTS: Eleven retrospective studies were included in this Meta-analysis. No significant difference between early and late surgery was observed for IXT patients (ORFirst follow-up= 0.88, 95%CI 0.53-1.44, P=0.61; ORFinal follow-up=1.48, 95%CI 0.94-2.31, P=0.09). However, sensitivity analysis performed by sequentially omitting individual studies showed that the final follow-up result was not stable. Subgroup analyses revealed that an earlier surgical procedure could lead to a better outcome in the 4-year boundary subgroup as well as the bilateral lateral rectus recession (BLR) subgroup for the final follow-up (OR4y=2.64, 95%CI 1.57-4.44, P=0.00; ORBLR=2.25, 95%CI 1.36-3.74, P=0.00). CONCLUSION: Early surgery for IXT provides a better long term follow-up outcome when patients are younger than 4 years old or choose the BLR surgical method.

The continuous increase in waste generation warrants global management of waste to reduce the adverse economic, social, and environmental impact of waste while achieving goals for sustainability. The complexity of waste management systems due to different waste management practices renders such systems difficult to analyze. System dynamics (SD) approach aids in conceptualizing and analyzing the structure, interactions, and mode of behavior of the complex systems. The impact of the underlying components can therefore be assessed in an integrated way while the impact of possible policies on the system can be studied to implement appropriate decisions. This review summarizes various applications of SD pertinent to the waste management practices in different countries. Practices may include waste generation, reduction, reuse/recovery, recycling, and disposal. Each study supports regional-demanding targets in environmental, social, and economic scopes such as expanding landfill life span, implementing proper disposal fee, global warming mitigation, energy generation/saving, etc. The interacting variables in the WMS are specifically determined based on the defined problem, ultimate goal, and the type of waste. Generally, population and gross domestic product can increase the waste generation. An increase in waste reduction, source separation, and recycling rate could decrease the environmental impact, but it is not necessarily profitable from an economic perspective. Incentives to separate waste and knowledge about waste management are variables that always have a positive impact on the entire system.

Objective Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans. Methods Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years. Results The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up. Conclusions This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.

Background Peripheral helper T (TPH) cells, a recently defined subset of Th cells, promote B cell differentiation and antibody production in inflamed tissues. This study investigated whether circulating TPH cells are associated with primary biliary cholangitis (PBC), a typical organ-specific autoimmune disease. Methods Twenty PBC patients and 20 age- and sex-matched healthy controls (HCs) were recruited. The circulating TPH cell subsets were analyzed by flow cytometry, and the associations of TPH cells with disease activity and plasma cells were determined. Functional analysis was performed using a TPH and B cell coculture experiment. Results The frequencies of circulating TPH cells, ICOS+ TPH cells, and CD28+ TPH cells were increased in patients with PBC. Furthermore, the ICOS+ TPH cell level was higher in PBC patients with or without cirrhosis than in HCs, and the level decreased after treatment. Moreover, ICOS+ TPH cell levels correlated positively with specific clinical parameters (including anti-mitochondrial antibodies against M2 antigen (AMA-M2), IgM) and plasma cell levels, suggesting that the TPH cell activation status is associated with the severity of PBC. Coculture results revealed an enhanced ability of TPH cells from PBC patients to induce B cell differentiation. Conclusions Elevated numbers of TPH cells may be involved in the pathogenesis of PBC, and the activation status of TPH cells is related to the severity of PBC. Additionally, TPH cells can be used as a useful biomarker for evaluating the progression of PBC and may serve as a therapeutic target for PBC patients in the future.

Purpose - The present study aimed to identify differently expressed peptides involved in BC as potential biomarkers. Experimental Design - The serum proteomic profiling of 128 serum samples from 64 BC patients and 64 healthy controls (HC), using magnetic beads based immobilized metal ion affinity chromatography (MB-IMAC-Cu) separation followed by MALDI-TOF MS. ClinProTools software identified a number of distinct markers. Then, we performed liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to identify the candidate serum biomarker based on serum proteomics analysis. Finally, enzyme-linked immunosorbent assays (ELISAs) were used to verify the expression of the candidate serum biomarker in BC patients. Results - BC patients could be identified with sensitivity of 87.32% and specificity of 89.46%. Of 41 m/z peaks that differed between BC and HC, six peaks were significantly different between BC and HC (P0.01, fold change1.5), with peak 1 upregulated and peaks 2-6 downregulated in the BC group. The upregulated peak 1 (m/z: 6638.63) is identified as a region of apolipoprotein C1 (APOC1), and validation showed that APOC1 expression increased from healthy controls to those with FA as well as mastopathy, and finally BC patients. Conclusions and Clinical Relevance - The present study indicates that APOC1 could serve as a candidate serum diagnostic biomarker for BC.

Stage 1 hypertension, newly defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline, has been the subject of significant interest globally. This study aims to assess the impact of the new blood pressure (BP) stratum on subsequent subclinical cardiovascular outcomes in low‐risk young adults. This longitudinal study consisted of 1020 young adults (47.7% female; ages 18–23 years) free of cardiovascular disease from the Hanzhong Adolescent Hypertension Cohort with up to 25‐year follow‐up since 1992–1995. Outcomes were available through June 2017. Young adults with stage 1 hypertension accounted for 23.7% of the cohort. When it comes to middle adulthood, subjects with early life stage 1 hypertension were more likely to experience BP progression, and they had a 1.61‐fold increased risk of high‐risk brachial‐ankle pulse wave velocity (baPWV) and a 2.92‐fold risk of left ventricular hypertrophy (LVH) comparing with their normotensive counterparts. Among participants without any active treatment in midlife, the risk associated with stage 1 hypertension for BP progression was 2.25 (95% confidence interval [CI] = 1.41–3.59), high‐risk baPWV was 1.58 (95% CI = 1.09–2.79), LVH was 2.75 (95% CI = 1.16–6.48), and subclinical renal damage (SRD) was 1.69 (95% CI = 1.02–2.82) compared with the normal BP group. Overall, young adults with stage 1 hypertension had significantly higher risks for midlife subclinical cardiovascular outcomes than normotensive subjects. BP management targeting low‐risk young adults is of importance from both clinical and public health perspectives.

Background In patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non-motor symptoms may fluctuate in a manner similar to motor symptoms. Objectives To validate a final version of a patient-rated questionnaire that captures the presence and severity of non-motor fluctuations in levodopa-treated PD patients (NoMoFA). Methods We recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test-retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire. Results Two hundred subjects and their care-partners participated in the study (age: 66.4 ± 9.6 years; disease duration: 9 ± 5.5 years; median Hoehn and Yahr [HY mean Unified Parkinson's Disease Rating Scale (UPDRS) III ON score: 27.4 ± 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach's alpha was 0.894. While eight items had "item-to-total" correlations below the cutoff of 0.4, removing these items did not improve Cronbach's alpha. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64-0.80). Concurrent validity was adequate with all Spearman's rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy. Conclusions The final 27-item self-administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non-motor symptoms in PD. © 2021 International Parkinson and Movement Disorder Society.

To improve the performance of optoelectronic devices, a high performance wide angle SiO2/Ti3O5 Distributed Bragg Reflector (DBR) mirror was designed and fabricated on double polished sapphire substrate. 17-pairs gradually varied DBR structure was applied in order to acquire a broad stopband reflectivity over 95% from 400 nm to 800 nm, covering the whole visible light region. The DBR mirrors deposited at the backside of optoelectronics devices are also demonstrated to remain a high reflectivity at wide incident angles, which improves the emission efficiency of LEDs and light absorption efficiency of InGaN/GaN photoelectrochemical cell (PEC).

The microinsurance market suffers from severe market failures; thus, government interventions are increasingly used to stimulate its functioning. Our article evaluates, from a law and economics perspective, whether these interventions are effective in increasing access to insurance without inducing moral hazard and adverse selection. We then use this framework to evaluate typical types of government interventions in the Chinese microinsurance market (subsidisation, simplification, use of group policy and established distribution channels). Using practical cases, we further identify solutions to remedy the market frictions induced by government interventions. We find that government interventions are only effective under certain conditions: (1) stable and smartly designed subsidies are provided or innovative market practices are subsidised; (2) insurance policies are easy to understand; (3) product distributors are properly trained or licensed; (4) group policies can be renewed.

Introduction: Programming directional leads poses new challenges as the optimal strategy is yet to be established. We designed a randomized control study to establish an evidence-based programming algorithm for patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation with directional leads. Methods: Fourteen consecutive patients were randomized to programming with either early or delayed (i.e., starting with a “ring mode”) steered stimulation. Motor scores, number of programming visits, calls to the clinic, battery consumption, and stimulation adjustments required were recorded and compared between groups, using the Wilcoxon signed-ranks test, after 3 months of open-label programming. Results: Thirteen patients (25 electrodes) were included, of which 23 were steerable. Nine out of 14 electrodes allocated to delayed steered stimulation were changed to steered mode due to side effects during the course of the study. No patients (11 electrodes) initially allocated to early steered stimulation were converted to ring mode. The 2 study arms did not differ in any of the considered measures at 3 months. Conclusion: Programming with early or delayed steered stimulation is equally effective in the short term. However, delayed steering is less time consuming and is not always needed.

Background Low back pain (LBP) is one of the most common occupational injuries that nurses experience in their daily work, which ultimately causes disability or difficulty in performing heavy physical activity. There is scarce information that presents a direct figure about the prevalence of LBP in Chinese nurses. Objective To systematically review and analyze the prevalence and influencing factors of LBP among nurses in China. Methods Related literature extracted from PubMed, Web of Science, Scopus, China National Knowledge Infrastructure databases were selected and reviewed based on the PRISMA guideline. Random effects models were used for data analysis, where heterogeneity was tested through I2. Egger's test was used to analyze the literature publication bias. Results The combined data indicated that the prevalence of LBP among nurses in China was 78% [95% confidence interval (CI) = 0.72–0.83]. The prevalence of LBP among nurses in China has declined in the past decade. Nurses presented a high risk of LBP in terms of female (OR = 2.38, 95% CI = 1.23–3.44, P < 0.0001), married (OR = 2.79, 95% CI = 1.57–3.86, P < 0.0001), 24 ≤ BMI < 28 (OR = 2.03, 95% CI = 1.18–3.08, P < 0.0001), and working for more than ten >10 years (OR = 2.54, 95% CI = 2.03–3.32, P < 0.0001). Conclusions There is a high prevalence of LBP among nurses in China. Interventions that include healthy dietary habits and physical activity mainly focusing on female married nurses who are working for at least 10 years should be implemented. Furthermore, nurses ought to apply ergonomic principles for personal protection at the workplace.

Background No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD). Objective Study's objective was to compare the efficacy and safety of levodopa versus dopamine agonist monotherapy after deep brain stimulation (DBS) in PD. Methods Thirty-five surgical candidates were randomly assigned to receive postoperative monotherapy with either levodopa or dopamine agonist in a randomized, single-blind study. All patients were reevaluated in short- (3 months), mid- (6 months), and long-term (2.5 years) follow-up after surgery. The primary outcome measure was the change in the Non-Motor Symptoms Scale (NMSS) 3 months after surgery. Secondary outcome measures were the percentage of patients maintaining monotherapy, change in motor symptoms, and specific non-motor symptoms (NMS). Analysis was performed primarily in the intention-to-treat population. Results Randomization did not significantly affect the primary outcome (difference in NMSS between treatment groups was 4.88 [95% confidence interval: -11.78-21.53, P = 0.566]). In short- and mid-term follow-up, monotherapy was safe and feasible in more than half of patients (60% in short- and 51.5% in mid-term follow-up), but it was more often possible for patients on levodopa. The ability to maintain dopamine agonist monotherapy was related to optimal contact location. In the long term, levodopa monotherapy was feasible only in a minority of patients (34.2%), whereas dopamine agonist monotherapy was not tolerated due to worsening of motor conditions or occurrence of impulse control disorders. Conclusions This trial provides evidence for simplifying pharmacological treatment after functional neurosurgery for PD. The reduction in dopamine receptor agonists should be attempted while monitoring for occurrence of NMSs, such as apathy and sleep disturbances. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background/objectives Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time. Subjects/methods To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD. Results In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR). Conclusions In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD.

The resistive switching (RS) behavior of a gallium oxide (Ga2O3) thin film for use in resistive random access memory (RRAM) was investigated. Ta/Ga2O3/Pt memory devices exhibited favorable RS behavior, such as a small distribution of switching parameters and switching cycles of more than 3 × 106. X-ray photoelectron spectroscopy and the current transport mechanism indicated that that the RS behavior was attributed to the local variation on the Schottky barrier near the Pt electrode interface due to oxygen vacancies. A hybrid system for self-powered data storage and deletion was built by combining the RRAM device with a commercial Pb(Zr1-xTix)O3 piezoelectric ceramic as a pressure sensor/power generator. The excellent anti-interference and reuse performance of the system indicated promising potential for the application of this memory device.

Transforming growth factor β (TGF-β)/Smad3 signaling plays a central role in chronic heart disease. Here, we report that targeting Smad3 with a Smad3 inhibitor SIS3 in an established mouse model of hypertension significantly improved cardiac dysfunctions by preserving the left ventricle (LV) ejection fraction (LVEF) and LV fractional shortening (LVFS), while reducing the LV mass. In addition, SIS3 treatment also halted the progression of myocardial fibrosis by blocking α-smooth muscle actin-positive (α-SMA+) myofibroblasts and collagen matrix accumulation, and inhibited cardiac inflammation by suppressing interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP1), intercellular cell adhesion molecule-1 (ICAM1) expression, and infiltration of CD3+ T cells and F4/80+ macrophages. Interestingly, treatment with SIS3 did not alter levels of high blood pressure, revealing a blood pressure-independent cardioprotective effect of SIS3. Mechanistically, treatment with SIS3 not only directly inactivated TGF-β/Smad3 signaling but also protected cardiac Smad7 from Smurf2-mediated proteasomal ubiquitin degradation. Because Smad7 functions as an inhibitor for both TGF-β/Smad and nuclear factor κB (NF-κB) signaling, increased cardiac Smad7 could be another mechanism through which SIS3 treatment blocked Smad3-mediated myocardial fibrosis and NF-κB-driven cardiac inflammation. In conclusion, SIS3 is a therapeutic agent for hypertensive heart disease. Results from this study demonstrate that targeting Smad3 signaling with SIS3 may be a novel and effective therapy for chronic heart disease., Graphical Abstract, Meng and colleagues developed a novel and effective therapy for hypertensive heart disease by specifically targeting Smad3, a key mediator of downstream TGF-β signaling, with a Smad3 inhibitor SIS3. They found that SIS3 treatment significantly improved cardiac dysfunctions and suppressed myocardial fibrosis and inflammation in an established mouse model of hypertension.

Corruption has been a major obstacle to economic growth around the world. In this paper, we examine how firms interact with corrupt government officials either to minimize the impact of corruption on their operations or to maximize their benefit of paying a bribe. Our estimates show that firms know exactly what they need and use their limited resources to bribe only relevant government authorities. In other words, firms are rational bribers who know exactly what they need and optimize their bribes to fulfill that need. This type of intentional bribery could be reduced by enhanced institutional environments and improved openness of the economy.

The efficacy and safety of low-dose anti-PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1-6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto-HSCT]: 18%), the overall response rate (ORR) by positron emission tomography-computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%). Median cumulative dose for achieving best response was 400 (300-800) mg. Median progression-free survival (PFS) was 35 months. Median overall survival (OS) was not reached. Adverse events (AEs) of grade 1-2 were observed in three patients. In the nivolumab cohort (N = 6), who had failed a median of three (2-6) therapies (BV: 50%; auto-HSCT: 17%; allogeneic HSCT: 34%), the ORR was 100% (mCR: 67%; PR: 17%; indeterminate response: 17%). Median cumulative dose for achieving best response was 160 (160-360) mg. Median PFS was 33 months. Median OS was not reached. AEs of grade 1-2 were observed in four patients, two of whom had pre-existing autoimmune conditions. Five patients with Epstein-Barr virus (EBV) positive Reed-Sternberg cells underwent monitoring of plasma EBV DNA, which became negative in four mCR patients but remained positive in one PR patient who died ultimately from refractory lymphoma. Low-dose pembrolizumab and nivolumab were highly efficacious and safe in relapsed/refractory cHL. These observations have significant financial implications in resource-constrained settings.

Background Dyslipidemia is a disorder of lipid metabolism and associated with insulin resistance. The relationship between longitudinal body mass index (BMI) changes from childhood to adulthood and long-term dyslipidemia was explored in this study. Methods We assessed the longitudinal relationship between BMI changes since childhood and dyslipidemia among 1738 participants in rural areas of Hanzhong City, Shaanxi. All participants were initially examined between the ages of 6 and 15 years in 1987 and were reexamined in 1995, 2013 and 2017; the total follow-up duration was 30 years. Anthropometric measurements and blood biochemistry indexes were measured. Results We found that gradual progression of normal weight to overweight (OR = 1.65; 95% CI = 1.27, 2.15) or persistent overweight (OR = 2.45; 95% CI = 1.52, 3.96) from childhood to adulthood was associated with an increased risk of dyslipidemia in adulthood. And these risks were largely disappeared if the overweight or obesity during childhood was resolved by adulthood. The higher the BMI in adulthood and the younger the age at which overweight begins, the higher the risk of dyslipidemia. Conclusions Early weight loss and any degree of weight loss from childhood to adulthood can help improve dyslipidemia in adulthood. We further emphasize the importance of weight management and control in public health primary prevention.

In order to improve fault feature extraction and diagnosis for rolling bearings, a fault diagnosis method based on fast dynamic time warping (fastDTW) and an adaptive Gaussian-Bernoulli deep belief network (AGBDBN) is proposed in this paper. Firstly, for the non-stationary vibration signal characteristics of the bearing, the fastDTW algorithm is used to calculate the residual vector of the fault signal, thereby enhancing the fault characteristic information. Then, according to the continuous vibration value of the bearing vibration signal, a standard deep belief network (DBN) is improved to deal with the problem that the optimal setting for the learning rate is difficult to achieve in the deep neural network training process and the AGBDBN model is used for fault diagnosis. Finally, the proposed method is compared with a variety of model diagnosis methods. The experimental results show that the proposed method achieved good diagnostic results.

In order to improve the accuracy of the segmentation of the breast ultrasound image lesion, Attention-Unet was improved, and an Attention-enhancing Unet (AE-Unet) model is proposed. First, the network loss function was improved. Based on the output value of the traditional network end, output weights of all attention gate were integrated. Compared with the standard lesion template, it was used to obtain accurate network loss values; Secondly, the network training method was improved, and the strategy of combining thickness and fineness was adopted. The overall loss function was used to train the overall network to make the network basically stable; then the partial loss function was used to alternately train the backbone network and the attention gate module in turn. Fine-tuning was used to further improve the accuracy of network parameters. The combination of the two greatly improves the accuracy of segmentation of the breast ultrasound lesion area. The experimental results on the breast ultrasound data actually collected in the hospital show that the proposed AE-Unet model has an M-IOU of 81.24%, precision of 85.88%, F1 of 80.58%, Acc of 93.85% and specificity of 97.48%, PPV is up to 85.88%, which has achieved better segmentation results than existing advanced algorithms.

Dual-active-bridge (DAB) circuit is an excellent candidate for a high-efficiency, high-power density, and bidirectional electric vehicle charger. Unlike resonant circuits employing auxiliary inductors and capacitors, DAB minimizes the usage of passive components. The challenge, however, lies in the difficulty of securing zero-voltage switching (ZVS), particularly at light-to-medium load when using the conventional single-phase-shift (SPS) control. This is of utmost importance not only for the sake of the efficiency, but also for minimizing the switch-bridge crosstalk caused by the hard switching- on , thereby enhancing the system reliability. Although dual-phase-shift (DPS) and triple-phase-shift (TPS) can be the answer, they do introduce side effects such as larger switching- off current. This article systematically integrates SPS, DPS, and TPS to maximize full-power ZVS range for both steady state and transient operations in EV chargers. This article plots ZVS boundaries over the full power range, categorizes all operations into nine modes, and proposes a smooth transition method among all operation modes. Dead band is also incorporated in the ZVS boundary setting. Experimental results on a SiC-based charger validate the effectiveness of this method of widening ZVS range for output voltage of 200–450 Vdc and power of 0–20 kW, achieving smooth transitions among various operation modes, and suppressing the switch crosstalk, thereby securing high charger reliability.

A compact planar directional coupled crossover with a wide fractional bandwidth is proposed in this letter, which is composed of overlapping planar 3-dB couplers based on the substrate integrated waveguide (SIW) and stripline techniques. In the proposed structure, the TE10 mode and TEM mode can be transmitted simultaneously without any interaction, which is helpful to design and integrate the SIW and stripline couplers for realizing a wideband directional coupled crossover with a compact footprint. A prototype with a center frequency of 26 GHz for 5G applications is designed and fabricated. The experimental results show that the measured crossover has high isolation among all ports and good directional coupling performance in orthogonal directions. The proposed crossover has a compact footprint and low loss, which can be a good candidate for developing the miniature feeding networks for multiple beam antennas.

Background The pathogenesis underlying the alterations of orbital architecture in Graves’ orbitopathy (GO) is not yet fully understood. The present study aimed to investigate the association of DNA methylation in peripheral blood and orbital volumetry in Chinese patients with GO. Methods A total of 35 GO subjects (70 orbits) were subjected to CT scan. The total cross-sectional area of the extraocular muscles (orbital muscles, OM), total orbit area (TOA), and the exophthalmometry were measured and OM/TOA ratio was calculated. Targeted bisulfite sequencing was performed on seven candidate genes. Results No significant correlation was established between the DNA methylation levels of these genes and exophthalmometry. The MBP methylation level was found to be correlated with OM/TOA ratio (P < 0.05). Multiple linear regression analysis on parameters including age, sex, TRAb, duration of GO, and DNA methylation levels of seven genes with OM/TOA ratio confirmed that MBP and OM/TOA ratio had a significant correlation (P < 0.05). The partial least squares analysis showed that the top three genes with the highest loadings were MBP, BOLL, and BECN1 and that OM/TOA ratio affected the DNA methylation block than exophthalmometry. Conclusions This study provided preliminary evidence that MBP is a potential gene associated with OM enlargement in GO patients according to the combination of DNA methylation sequencing and orbital CT measurement.