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Abstract Background SHR-1707 is a novel humanized anti-Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques or to promote the microglial phagocytosis of Aβ. Preclinical studies showed that SHR-1707 reduced brain Aβ deposition in 5xFAD transgenic mice. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR-1707 in healthy adult subjects. Methods Two randomized, double-blind, single-ascending-dose, phase 1 studies were conducted in China (Study CHN) and Australia (Study AUS). Study CHN consisted of 2 parts. In Part 1, eligible healthy young adults (18–45 years) were sequentially randomized 8:2 to receive SHR-1707 (five cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in Part 2, elderly subjects (55–80 years) were randomized 8:4 to receive SHR-1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across three dosing cohorts (2, 20, and 60 mg/kg). Results Sixty-two (part 1/2, n = 50/12; age range, 18–42/55–63 years) and 30 subjects (age range, 18–42 years) received SHR-1707 or placebo in Study CHN and Study AUS, respectively. In Study CHN, all treatment-related adverse events (TRAEs) were mild, with the most common being transient laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR-1707/placebo); the most common TRAEs with SHR-1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR-1707 increased in a slightly greater than dose-proportional manner over the dose range of 2–60 mg/kg in young adults; there was a dose-dependent increase in plasma Aβ42 concentration following SHR-1707 administration compared with the placebo group. The safety and PK and PD profiles of SHR-1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety, PK and PD of SHR-1707 was observed. Conclusions A single intravenous dose of SHR-1707 at 2–60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK and PD profiles are supportive for further clinical development. Trial registration NCT04973189 (retrospectively registered on Jul.21, 2021) and NCT04745104 (registered on Feb.6, 2021) on clinicaltrials.gov.

Underwater acoustic target recognition has always played a pivotal role in ocean remote sensing. By analyzing and processing ship-radiated signals, it is possible to determine the type and nature of a target. Historically, traditional signal processing techniques have been employed for target recognition in underwater environments, which often exhibit limitations in accuracy and efficiency. In response to these limitations, the integration of artificial intelligence (AI) methods, particularly those leveraging machine learning and deep learning, has attracted increasing attention in recent years. Compared to traditional methods, these intelligent recognition techniques can autonomously, efficiently, and accurately identify underwater targets. This paper comprehensively reviews the contributions of intelligent techniques in underwater acoustic target recognition and outlines potential future directions, offering a forward-looking perspective on how ongoing advancements in AI can further revolutionize underwater acoustic target recognition in ocean remote sensing.

The dynamic coefficients (dynamic stiffness coefficient and dynamic damping coefficient) of gas foil bearings (GFBs) are important for transient dynamics calculation and stability analysis of the GFBs-rotor system. Although the perturbation method can be used to calculate the dynamic coefficients, it can only consider a single whirl ratio. Moreover, the whirl ratio is assumed and not practical. Therefore, this paper proposes an identification method of dynamic coefficients of GFBs by simulated excitation. Firstly, based on single journal-single GFB model considering gas-structure interaction by coupled fields, harmonic excitations were applied to the rotor to obtain the shaft orbit. Next, frequency response function method and equivalence coefficient method were used to identify dynamic coefficients. The former method is suitable for the case where response and excitation are same frequency, namely linear problem. The latter method is fit for the situation in which the response has multiple frequency components, namely nonlinear problem. Finally, examples were carried out, and the results from different methods were compared and analyzed. This research work lays a theoretical foundation for the design of the GFBs-rotor system.

Abstract Single image dehazing has received a lot of concern and achieved great success with the help of deep-learning models. Yet, the performance is limited by the local limitation of convolution. To address such a limitation, we design a novel deep learning dehazing model by combining the transformer and guided filter, which is called as Deep Guided Transformer Dehazing Network. Specially, we address the limitation of convolution via a transformer-based subnetwork, which can capture long dependency. Haze is dependent on the depth, which needs global information to compute the density of haze, and removes haze from the input images correctly. To restore the details of dehazed result, we proposed a CNN sub-network to capture the local information. To overcome the slow speed of the transformer-based subnetwork, we improve the dehazing speed via a guided filter. Extensive experimental results show consistent improvement over the state-of-the-art dehazing on natural haze and simulated haze images.

Objectives: INS068 is a novel, soluble, and long-acting insulin analog. In this study, we evaluated the pharmacokinetics and relative bioavailability of two formulations of INS068 in healthy Chinese subjects: a reference formulation packaged in vials and administered via syringe (R), and a test formulation packaged and administered via pen injector (T).Methods: A randomized, open-label, two-period, two-sequence crossover study was conducted with 24 healthy Chinese subjects. Subjects were randomized and administered subcutaneously in the abdomen at 0.4 U/kg of test or reference INS068 injection according to an open crossover design. INS068 concentrations in the serum were measured using LC-MS/MS, and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC0–t and AUC0–∞) were used to evaluate relative bioavailability.Results: After a single dose at 0.4 U/kg, the median Tmax of INS068 was 12 h for both formulations, and the mean t1/2 for T and R was 13.0 h and 12.6 h, respectively. The geometric means of Cmax and AUC0–∞ were 3.99 nmol/L and 120 h·nmol/L for the T, and 4.05 nmol/L and 117 h·nmol/L for the R, respectively. The geometric mean ratios of Cmax, AUC0–t and AUC0–∞ of T over R were 98.7% (90% CI: 92.7%–105.2%), 102.6% (90% CI: 100.0%–105.3%) and 102.8% (90% CI: 100.1%–105.5%).Conclusion: The overall PK profile of the two formulations of INS068 injection was comparable in healthy subjects, and the pen injector of INS068 had adequate safety and tolerability, supporting it as a new formulation in a phase III study and bridging PK data from early phase clinical trials.Clinical Trial Registration:clinicaltrials.gov, identifier: NCT05336071

Objective To analyze the clinical data of elderly patients with peritoneal dialysis (PD) and compare patient and technique survival rates between Group 1 (65–74 years old) and Group 2 (≥75 years old).Methods This retrospective study enrolled 296 elderly patients (≥65 years old) on maintenance PD who were admitted to the Peritoneal Dialysis Center of the Second Hospital of Soochow University. The patients were categorized by outcome into ongoing PD, changed to hemodialysis, renal recovery dialysis stopped, or death groups. The patients were divided into Group 1 (65–74 years old) and Group 2 (≥75 years old). Patient survival and technique survival rates were calculated by the Kaplan–Meier method. Factors associated with patient survival were analyzed using the Cox regression model.Results There were 176 (59.5%) subjects in Group 1 and 120 (40.5%) subjects in Group 2. The primary causes of death were cardiovascular events, peritonitis, and other infections. The patient survival rates at 1, 3, and 5 years were 91.2%, 68.0%, and 51.3% in Group 1 and 76.8%, 37.5%, and 17.6% in Group 2 (p

Abstract To detect lanes at night, each detecting image is the fusion of the multiple images in a video sequence. The valid lane line detection region is identified on region merging. Then, the image preprocessing algorithm based on the Fragi algorithm and Hessian matrix is applied to enhance lanes; to extract the lane line center feature points, the image segmentation algorithm based on Fractional differential is proposed; and according to the possible lane line positions, the algorithm detects the centerline points in four directions. Subsequently, the candidate points are determined, and the recursive Hough transformation is applied to obtain the possible lane lines. Finally, to obtain the final lane lines, we assume that one lane line should have an angle between 25 and 65 degrees, while the other should have an angle between 115 and 155 degrees, if the detected line is not in the regions, the Hough line detection will be continued by increasing the threshold value until the two lane lines are got. By testing more than 500 images and comparing deep learning methods and image segmentation algorithms, the lane detection accuracy by the new algorithm is up to 70%.

Deep learning models can produce unstable results by introducing imperceptible perturbations that are difficult for humans to recognize. This can have a significant impact on the accuracy and security of deep learning applications due to their poorly understood interpretability. As a field critical to security research, this problem clearly exists in underwater acoustic target recognition for ocean sensing. To address this issue, this article investigates the reliability of state-of-the-art deep learning models by exploring adversarial attack methods that add small, exquisite perturbations on acoustic Mel-spectrograms to generate adversarial spectrograms. Experimental results based on real-world datasets reveal that these models can be forced to learn unexpected features when subjected to adversarial spectrograms, resulting in significant accuracy drops. Specifically, when employing the iterative attack method, the overall accuracy of all models experiences a significant decrease of approximately 70% for two datasets under stronger perturbations.

Abstract The objectives of this phase I study are to assess the safety, tolerability, and pharmacokinetics (PKs) of RO7049389 in healthy Chinese volunteers (HVs) and evaluate potential ethnic differences in the safety and PKs using data from this study and the first‐in‐human study (in which most of the HVs were non‐Asian). HVs randomly received a single dose of 200–600 mg of RO7049389 or a placebo in a single ascending dose (n = 28) or multiple doses of 200–400 mg of RO7049389 or a placebo in multiple ascending doses (n = 24). Safety and tolerability were monitored throughout the study. Serial blood samples were collected for PK analysis. RO7049389 was safe and well‐tolerated in the HVs. The time to maximum concentration ranged from 1.5 to 3.0 h, and terminal half‐life ranged from 3.66 to 14.6 h. A single dose of 200–600 mg and multiple doses of 200–400 mg exhibited nonlinear PKs. In general, the safety profiles were comparable between non‐Asian and Asian HVs, but the plasma exposure of RO7049389 in Chinese HVs was higher than that in non‐Asian HVs. The data generated from this study will provide guidance for future clinical studies on RO7049389 in Chinese/Asian patients with hepatitis B virus.

Nipah virus (NiV) is a newly emerged extremely dangerous zoonotic pathogen highly fatal to humans. Currently, no approved vaccine is available against NiV. This study employed a mammalian eukaryotic system to express NiV soluble G glycoprotein (NiV-sG), using CpG oligodeoxynucleotides (CpG)/Aluminum salt (Alum) as adjuvants to obtain a recombinant subunit vaccine candidate. We also evaluated the immunogenicity and efficacy of the protein in mice and pigs. The results showed that humoral and cellular immune responses were induced in all the vaccination groups in two animal models. The levels of specific and neutralizing antibodies and the proliferation levels of T helper(Th) cells were significantly higher than those in the control group. The protective efficacy of the subunit vaccines evaluated in the pseudovirus in vivo infection mouse model strongly suggested that this vaccine could provide protective immunity against NiV. A neoadjuvant (HTa) based on liposomes and cholera toxin combined with CpG/Alum was exploited and evaluated in mice. The neoadjuvant group showed a more protective efficacy than the CpG/Alum group. The aforementioned results indicated that the subunit vaccine could be used as a promising candidate vaccine for preventing Nipah virus infection.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a threat to the health of pigs worldwide, but commercially available vaccines offer limited protection against PRRSV infection. It is necessary to develop a more effective DNA vaccine. The immunological effects of DNA vaccines with three adjuvants were examined in pigs (Susscrofa domestica) challenged with PRRSV. These DNA vaccines, which encoded PRRSV GP3 and GP5, were formulated with A1, A2, and A3. Serum specific and neutralizing antibodies, IL-4, IFN-γ, IL-2, IL-10, CD4+ and CD8+T-lymphocytes, health status, histopathology, and viral loads were determined. The results showed that the use of adjuvant A3 led to higher levels of neutralizing antibodies and a lower viral load in pigs compared to the other adjuvants. The neutralizing antibody titers of the pVAX-GP35+A1 and pVAX-GP35+A3 groups reached a peak of 1:19 at 35 dpi. The maximum concentration of IL-4 was 136.77 pg/mL in the pVAX-GP35+A3 group. At 35 dpi, the IFN-γ concentration in the pVAX-GP35+A1 group was 227.4 pg/mL. pVAX-GP35+A3 group shows the highest IL-2 and IL-10 expression to the peak of 597.6 pg/mL and 189.1 pg/mL, respectively. We found a formulation demonstrated beneficial immune outcomes. This study provides an alternative vaccine to protect pigs from PRRSV.

Thousands of people die each year from Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV), probably due to exacerbation of the inflammatory response that impairs the course of the disease. Microglia are mononuclear phagocytic cells located within the parenchyma of the central nervous system; these play a key role in the innate immune response against JEV infections. However, the involvement of toll-like receptor 2 (TLR2) in the inflammatory response during the early stages of JEV infection in BV2 cells remains. Here, we evaluated protein profiles and determined the role of TLR2 in the inflammatory response of JEV-infected BV2 cells. High-depth tandem mass tags labeling for quantitative proteomics was used to assess JEV infected-BV2 cells and compare immune response profiles at 6, 12, and 24 h post-infection (hpi). In total, 212 upregulated proteins were detected at 6 hpi, 754 at 12 h, and 191 at 24 h. According to GO and KEGG enrichment analysis, the upregulated proteins showed enrichment for proteins related to the immune response. Parallel reaction monitoring tests, western blotting, and qPCR results showed that the adaptor protein MyD88 was not activated. The expression levels of key proteins downstream of MyD88, such as IRAK1, IRAK4, and TRAF6 did not increase; however, the expression levels of PI3K-AKT did increase. By inhibiting key proteins (TLR2, PI3K, and AKT) we confirmed that JEV activated TLR2, thus resulting in a robust inflammatory response. Consequently, the TLR2-PI3K-AKT signaling axis was proven to play a critical in the early stages of the JEV infection-induced inflammatory response in microglia.

This study investigates the influence of longitudinal through voids on vault lining. Firstly, a loading test was carried out on a local void model, and the CDP model was used for numerical verification. It was found that the damage to the lining caused by a longitudinal through void was primarily located at the void boundary. On the basis of these findings, an overall model of the vault’s through void was established using the CDP model. The effects of the void on the circumferential stress, vertical deformation, axial force, and bending moment of the lining surface were analyzed, and the damage characteristics of the vault’s through void lining were studied. The results indicated that the through void of the vault caused circumferential tensile stress on the lining surface of the void boundary, while the compressive stress of the vault increased significantly, resulting in a relatively uplifted vault. Furthermore, the axial force within the void range decreased, and the local positive bending moment at the void boundary increased significantly. The impact of the void increased gradually with the height of the void. If the height of the longitudinal through void is large, the inner surface of the lining at the void boundary will crack longitudinally, and the vault will be at risk of falling blocks or even being crushed.

Abstract Background Gout treatment is not optimized globally, often due to therapeutic inertia by physicians or poor adherence to urate‐lowering medications by patients. A patient decision aid (PDA) to facilitate shared decision making (SDM) in gout treatment may overcome these physician‐patient barriers. Objective The study explored the views of physicians and patients on a novel locally designed gout treatment PDA prototype. Design Qualitative descriptive design was used to gather data from in‐depth‐interviews (IDI) and focus group discussions (FGD). Data analysis was via thematic analysis. Emergent themes shaped a revised version of the PDA. Setting and participants Adult Asian patients with recent acute gout exacerbations and local Primary Care Physicians (PCP) in Singapore were purposefully chosen. 15 patients with gout and 11 PCPs participated across three IDIs and six FGDs, with the investigators exploring their views of a prototype gout treatment PDA. Results Patients and physicians generally concurred with the content and design of the PDA prototype. However, while patients preferred fewer treatment details, the PCPs desired more information. Patients preferred the display of statistics, while PCPs felt that numbers were not relevant to patients. The latter were hesitant to include treatment options that were unavailable in primary care. Both stakeholders indicated that they would use the PDA during a consultation. PCPs would need further training in SDM, given a lack of understanding of it. Conclusion and patient contribution Patients will be the prime users of the PDA. While their views differed partially from the physicians, both have jointly developed the novel gout treatment PDA.

Geoacoustic inversion is a challenging task in marine research due to the complex environment and acoustic propagation mechanisms. With the rapid development of deep learning, various designs of neural networks have been proposed to solve this issue with satisfactory results. As a data-driven method, deep learning networks aim to approximate the inverse function of acoustic propagation by extracting knowledge from multiple replicas, outperforming conventional inversion methods. However, existing deep learning networks, mainly incorporating stacked convolution and fully connected neural networks, are simple and may neglect some meaningful information. To extend the network backbone for geoacoustic inversion, this paper proposes a transformer-based geoacoustic inversion model with additional frequency and sensor 2-D positional embedding to perceive more information from the acoustic input. The simulation experimental results indicate that our proposed model achieves comparable inversion results with the existing inversion networks, demonstrating its effectiveness in marine research.

Objectives Concerns are increasing about the clinical characteristics of gram- negative bacterial peritonitis for providing reference for clinical diagnosis, treatment and prevention. Methods A retrospective analysis was performed examining patients who developed peritoneal dialysis-related peritonitis (PDRP) from 1 January 2009 to 31 December 2018. Results Among 898 PD patients, 677 episodes of peritonitis occurred in 344 patients. Over 10 years, the proportion of gram-negative bacterial peritonitis increased from 0% to 26.15% (p = .045). E. coli was the leading cause (38.51%) of the 148 cases of gram-negative bacterial peritonitis. The increase of E. coli peritonitis between the first 5 and the last 5 years was obvious (20.45% vs. 46.15%). The antimicrobial sensitivity of gram-negative organisms to cefotaxime decreased from 71.43% to 55.84% (p = .017). In the gram-negative group, the effluent white cell count (WCC) on the first day was larger (OR: 1.374;95%CI: 1.248–1.563; p

In view of the characteristics of strong penetration and extremely sensitive to delamination of materials, ultrasonic wave has unique advantages in coating defect detection. In order to quickly and accurately detect the defects of the outer coating of submarine oil and gas pipelines, and make up for the weakness of the existing coating detection technologies for oil and gas pipeline, such as low reliability, vulnerable to external interference, inaccurate positioning, etc., a pipeline coating defect detection method using ultrasonic pulse echo was proposed. Through ANSYS modeling and simulation calculation, the attenuation characteristics of reflected echo between intact coating interface and defective coating interface were compared, and obvious differences can be seen in the amplitude of echo after multiple reflections. The fifth echo signal was selected as the basis for determining the coating defects, and the reliability of simulation results was verified by designed test. This study shows that the method has high sensitivity to accurately detect coating defects. The operation is simple and reliable, not affected by the submarine complex environment, and meets the needs of continuous detection, so it can guarantee the safe and efficient operation of submarine oil and gas pipelines.

Objectives To investigate the effects of climatic variables on peritoneal dialysis-associated peritonitis (PDAP) among patients receiving PD, such as seasonal variations in temperature and humidity. Methods A retrospective analysis was performed on PD patients, from 1 January 2011, to 31 December 2019. We evaluated the influence of seasonal factors on peritonitis rates and outcomes. Results Over the 9-year study period, 667 peritonitis episodes occurred, in 401 PD patients. Diarrhea-associated peritonitis occurred more frequently in summer compared with other seasons. Eating raw and cold food was identified as the primary cause of peritonitis in the summer. More peritonitis episodes occurred during summer. The peritonitis rate associated with gram-negative bacteria (p = 0.050) during summer was higher than those in all other seasons. The gram-negative bacterial peritonitis rate was positively correlated with monthly mean temperature (r = 0.504, p

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a major post-transcriptional regulator of low-density lipoprotein receptor degradation. Recently, PCSK9 was shown to be overexpressed by liver cells in rats with proteinuria. However, the levels of PCSK9 in newly diagnosed primary nephrotic syndrome (PNS) patients and correlations involving PCSK9 and blood lipids are not clearly understood. Methods One hundred and sixteen patients who were newly diagnosed with PNS were enrolled in this study. Results Plasma PCSK9 levels in PNS patients were significantly higher than those in healthy controls [310.86 (250.87, 390.25) ng/ml vs 255.67 (202.26, 320.26) ng/ml, p = 0.002]. Plasma PCSK9 in PNS patients was positively correlated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (γ = 0.246, p = 0.008, and γ = 0.183, p = 0.049). When plasma PCSK9 was >267.60 ng/ml, the risk of developing hypercholesterolemia significantly increased in PNS patients (OR = 6.40, 95% CI 2.06–19.87, p = 0.001). When plasma PCSK9 was >255.05 ng/ml, the risk of developing higher levels of LDL-C significantly increased in PNS patients (OR = 3.83, 95%CI 1.25–11.68, p = 0.018). Conclusions Plasma PCSK9 levels in newly diagnosed PNS patients were markedly increased, and elevated PCSK9 abundance was positively correlated with elevated serum TC and LDL-C levels, suggesting that PCSK9 may emerge as a novel therapeutic target in NS-associated hypercholesterolemia.

Heterogeneous and mobile wireless sensor networks (HMWSNs) are generally practical in constructing smart Internet of Things. However, malware can easily propagate itself over HMWSNs and make harm such as data interception and unauthorized activities. To defend such malware, developing a model to disclose dynamics of malware propagation becomes urgently required. In this context, a heterogeneous and mobile vulnerable-compromised-quarantined-patched-scrapped (VCQPS) model is proposed by considering both the heterogeneity and mobility of HMSNs (heterogeneous and mobile sensor nodes). Then, differential equations of transition proportions among all states are achieved by analyzing the changeable quantities of HMSNs belonging to different states. Further, the existence of the stationary points of the VCQPS model is proved, upon which the malware propagation threshold is derived by calculating the reproduction number. The stability of the malware-free stationary-point is also proved. Experiments are performed to validate the stability of the malware-free stationary-point and show the effectiveness of the VCQPS model by comparing our model with traditional SIS and SIR models.

Japanese encephalitis virus (JEV), which uses a mosquito primary vector and swine as a reservoir host, poses a significant risk to human and animal health. JEV can be detected in cattle, goats and dogs. A molecular epidemiological survey of JEV was conducted in 3105 mammals from five species, swine, fox, racoon dog, yak and goat, and 17,300 mosquitoes from 11 Chinese provinces. JEV was detected in pigs from Heilongjiang (12/328, 3.66%), Jilin (17/642, 2.65%), Shandong (14/832, 1.68%), Guangxi (8/278, 2.88%) and Inner Mongolia (9/952, 0.94%); in goats (1/51, 1.96%) from Tibet; and mosquitoes (6/131, 4.58%) from Yunnan. A total of 13 JEV envelope (E) gene sequences were amplified in pigs from Heilongjiang (5/13), Jilin (2/13) and Guangxi (6/13). Swine had the highest JEV infection rate of any animal species, and the highest infection rates were found in Heilongjiang. Phylogenetic analysis indicated that the predominant strain in Northern China was genotype I. Mutations were found at residues 76, 95, 123, 138, 244, 474 and 475 of E protein but all sequences had predicted glycosylation sites at ′N154. Three strains lacked the threonine 76 phosphorylation site from non-specific (unsp) and protein kinase G (PKG) site predictions; one lacked the threonine 186 phosphorylation site from protein kinase II (CKII) prediction; and one lacked the tyrosine 90 phosphorylation site from epidermal growth factor receptor (EGFR) prediction. The aim of the current study was to contribute to JEV prevention and control through the characterization of its molecular epidemiology and prediction of functional changes due to E-protein mutations.

To study the mechanism of vault lining under different void heights and verify the strengthening effect of the attached steel plate, a CDP (concrete-damaged plasticity) model and the XFEM (extended finite element method) were used to construct the local numerical model of the vault void, and an experiment was carried out for verification. The strengthened structure of the steel plate was assembled with a combination of a two-component epoxy adhesive and chemical anchor bolts. Five lining models with various void thicknesses, together with their strengthened models, were evaluated. The results of the established numerical model were compared with the experimental results in terms of failure mode, vertical displacement, and load-deformation results. The results of the two numerical models were in good agreement with the experimental results, revealing the failure mechanism of the vault lining. The rigidity of the specimen after steel plate strengthening was significantly improved. When the void height was one-fourth of the secondary lining thickness, the lining cracks were reduced from 14 to 4, and the distribution width of the cracks was also reduced from 1.047 to 0.091 m after steel plate strengthening. The level of damage caused by cracking was significantly reduced, which proves the effectiveness of the surface-sticking method for steel plate strengthening.

Objectives: The objective of this work was to study the results of urine drug testing for ritalinic acid (RA), the major urinary metabolite of methylphenidate (MP) (e.g., Ritalin®). The impact of age from 4 to 65 years old and older on median levels of RA was investigated as well as potential variations in pH, specific gravity and creatinine content of the patient urine samples. Design and Methods: Samples from patients who were 1) prescribed MP and found to be positive for RA, 2) prescribed MP but found to be negative for RA and 3) not prescribed MP but tested positive for RA were examined by liquid chromatography – mass spectrometry/mass spectrometry (LC-MS/MS) for RA concentration. The levels of RA were examined for median and average levels and further normalized and transformed to reveal a near gaussian distribution. Results: Over 20,000 samples from patients who were prescribed MP were examined for this work. Analysis of these data for a subset of patients prescribed MP and testing positive for RA revealed statistically different median values of RA for school age patients of 6 years old through 17 years old from adult patients 18 through 64 years old. Another 6751 samples were positive for RA without a prescription but were not included in the overall assessment of these data. Conclusions: While not clear as to the reason, these data indicate that school age children under the age of 18 have much higher levels of RA than adult patients. These results can be used to estimate “normal” levels of RA in these chronically dosed populations.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker β-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti–SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis.Clinical Trial Registration:http://www.clinicaltrials.gov, NCT03870100.

Heterogeneous wireless sensor networks (WSNs) are widely deployed, owing to their good capabilities in terms of network stability, dependability, and survivability. However, they are prone to the spread of malware because of the limited computational capabilities of sensor nodes. To suppress the spread of malware, a malware spread model is urgently required to discover the rules of malware spread. In this paper, a heterogeneous susceptible-iNsidious-infectious-recovered-dysfunctional (SNIRD) model was proposed, which not only considers the communication connectivity of heterogeneous sensor nodes but also reflects the characteristics of malware hiding and dysfunctional sensor nodes. Then, the fraction evolution equations of heterogeneous sensor nodes in different states in discrete time were obtained. Furthermore, the existence of equilibria for the heterogeneous SNIRD model was proved, and the malware spread threshold was obtained, which indicates whether malware will spread or fade out. Finally, the heterogeneous SNIRD model was simulated and it was contrasted with the conventional SIS and SIR models to validate its effectiveness. The results construct a theoretical guideline for administrators to suppress the spread of malware in heterogeneous WSNs.

Objectives: The aim of the study was to evaluate the laboratory parameters and symptoms after parathyroidectomy (PTX) in dialysis patients with secondary hyperparathyroidism (SHPT), and to briefly analyze the different therapeutic effects of the three surgical methods. Methods: A total of 182 dialysis patients who underwent PTX between February 2012 and January 2018 at the Second Affiliated Hospital of Soochow University were included in this study and followed for 12 months. Laboratory parameters such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were measured before and after operation. According to the follow-up time and type of operation, we calculated the percentage of laboratory indicators reaching the recommended range of the KDIGO guidelines after surgery. We also analyzed the improvement of bone pain and pruritus, as well as surgical complications. Results: After the operation, the levels of iPTH, Ca, and P decreased significantly at each time point. ALP increased at the first postoperative week and gradually decreased to normal range after 3 months. Symptoms, such as bone pain and pruritus, were significantly relieved. According to the follow-up time and three surgical methods (subtotal parathyroidectomy, total parathyroidectomy, total parathyroidectomy plus autologous transplantation), we found that the ratio of each laboratory parameter reaching the recommended range of KDIGO guidelines was significantly different. Conclusion: PTX is a safe and effective therapy for treating SHPT that is refractory to medical therapies and accompanied by related signs and symptoms in dialysis patients. All three operative techniques were effective in controlling SHPT.

In waterproofing mountain tunnels, the tunnel joint is the weak link. To explore the waterproof failure mechanism of the tunnel joint waterstop belt and to propose an optimization method for the waterstop belt, this paper combines tests and numerical simulations, summarizes the waterproofing mechanism of the waterstop belt, establishes a finite element model of the waterstop belt considering bonding and extrusion, and studies the waterproofing ability and mechanical properties of the waterstop. The main conclusions are as follows: (1) The waterproofing capacity of the water stop belt depends on its surface contact pressure and bonding force. (2) Waterstop deformation will partially destroy the bonding between the waterstop and concrete, reducing the reliability of the waterproofing mechanism. (3) When the deformation of the waterstop belt reaches a certain degree, its stress value is too large to meet the requirements of its service life. (4) The design can be optimized from two aspects: the bond between the waterstop and concrete, and the size of the waterstop.

Until July 29th, the number of confirmed coronavirus (COVID-19) cases worldwide has risen to over 16 million, within which 655 k deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerges as the 11th global pandemic disease, showing the highest infectivity and lowest infection fatality rate. In this review, we compare the immunopathology among SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV2. SARS-CoV2 is similar to SARS-CoV; it can cause lymphocytopenia and a rising granulocyte count. Here we point out the human body and concentrated society make for an excellent incubator for virus evolution. Most research energies put into developing the SARS-CoV2 vaccine are trying to block virus infection. Sixty-five percent of severe patients die with multiple organ failure, inflammation, and cytokine storm, which indicates that the patient’s immune system maintains functionality. Finding a way to trigger the specific T cell subset and plasmablast in our body is the best shot to get away with SARS-CoV2.

Lean combustion technique and annular geometries are preferred in aero-engines and gas turbines, which however may lead to azimuthal combustion instabilities. Active control can be used to stabilize combustion instabilities. Due to its easy use, linear feedback controllers embedded with linear flame response models under weak perturbation amplitude are typically preferred. However, flame responses to oncoming disturbances are typically nonlinear; such controllers are not guaranteed to stabilize. Model-based control strategies generally focus on axisymmetric cases, even though symmetry breaking of azimuthal thermoacoustic modes often occurs in annular combustors. This work uses an improved thermoacoustic model to simulate combustion instabilities within annular combustors, providing a platform on which control strategies development can be performed. The improved model takes into account the nonlinear flame response and the symmetry breaking of azimuthal modes. Single-input single-output control strategies targeting on these nonlinear instabilities are developed in this work. Such controllers can achieve stability for linear and nonlinear fluctuations as well as in symmetric and non-axisymmetric cases. The controllers adopt the H ∞ loop-shaping control strategy and a satisfactory robust performance is obtained.

BACKGROUND:Hepatitis C virus core antigen (HCV Ag) assay has been proposed as a more economical alternative to HCV RNA detection. This study aimed to investigate the clinical utility of HCV Ag assay in the monitoring of direct-acting antivirals (DAAs) for chronic hepatitis C patients. METHODS:We analyzed serum samples from 110 patients treated with paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin. The levels for both HCV Ag and HCV RNA assessed by COBAS TaqMan HCV (CTM) Test or Abbott RealTime HCV (ART) assay were evaluated at baseline, week 2, 4, and 12 during treatment and 12 weeks after completion. RESULTS:Baseline HCV Ag levels showed good correlations with HCV viral load (r = 0.879; p

An electromagnetic acoustic transducer (EMAT) is suitable for measuring the propagation time more accurately without causing abrasion to the transducer during testing due to the principle of its excitation. This work designs a flux-concentrating EMAT with a radial-flux-focusing permanent magnet to significantly enhance static magnetic field strength. Through theoretical analysis and finite element simulation, two kinds of coils are designed according to the concentration areas of the horizontal and vertical components of the magnetic field. One is used to generate pure longitudinal waves, and the other is used to generate both longitudinal waves and shear waves. The experimental comparison shows that the amplitudes of the pure longitudinal wave and the dual-mode wave excited by the two kinds of coils with the radial-flux-focusing magnet are more than two times higher than those with the ordinary magnet. Therefore, the flux-concentrating EMAT with the appropriate coil provides an insight into realizing more accurate detection where longitudinal wave detection is required.

Malware propagation is an important security problem faced by wireless sensor network (WSN).From the perspective of game theory,the microscopic mechanism of malware propagationin WSN was analyzed.The attack-defense game model of WSN was built,and the mixed Nash equilibrium solution of the model was obtained.With the solution,the infection probability of malware was determined and the theoretical model for the malware propagation in WSN was established.Meanwhile,a cellular automata model was proposed to simulate malware propagation process in WSN.Simulation experiments reveal the relationship between the propagation speed and the game parameters.The results of this study are of significance for people to formulate measures to reduce the propagation speed of malware.

To apply intrusion detection system (IDS) efficiently so as to suppress WSN malware propagation,a cloud-based network infrastructure for realizing functions of WSN IDS was presented,considering the real basis that the resources of WSN nodes were limited whilst the resources of cloud computing platform were almost unlimited.Based on the analysis of the game process between a sensor node and the corresponding WSN IDS agent,a WSN-malware-propagation-suppression game model was constructed by employing the dynamic Bayesian game,and the requirements of energy consumption in sending monitored data and privacy protection for sensor nodes were satisfied.According to the proposed game type and refined Bayesian equilibrium,the optimal strategie for suppressing WSN malware was proposed as well the algorithm for actual application was given.The factors that influence WSN IDS agents to select their optimal strategies were analyzed,and the experimental foundation was provided for the application of the proposed approach.

In the title organic salt, C17H20F2N3O3+·C8H4FO4−, proton transfer leads to one protonated lomefloxacin molecule (HLf+) and one 3-carboxy-5-fluorobenzoate (5-F-Hip−) anion in the asymmetric unit. The HLf+ cation is bent, with a dihedral angle of 38.3 (1)° between the quinoline ring and the piperazinium moiety. In the crystal, two kinds of N—H...O and O—H...O hydrogen-bonded chains cross-link each other to produce a three-dimensional network structure that is additionally stabilized by weak C—H...O and C—H...F hydrogen bonds, as well as π–π interactions. The methyl group attached to the piperazinium ring is disordered over two sets of sites [refined ratio: 0.645 (5):0.335 (5)], indicating the presence of both enantiomers of the cation in the structure.

Purpose: Tumor enucleation (TE) and partial nephrectomy (PN) have both become main treatment strategies for T1 renal cell carcinoma (RCC), despite the discrepancy between their safety margin. We performed a meta-analysis on all the relevant trials in order to compare the clinical efficacy and safety of TE with those of PN for RCC treatment.Methods: In this meta-analysis, randomized controlled trials or retrospective studies were included if they compared TE and PN therapy in patients with localized renal cancer. The main outcomes extracted were perioperative data and post-operative outcomes. Subgroups for analyses were undertaken according to tumor size and duration of follow up. Data were pooled using the generic variance method with a fixed or random effects model and expressed as mean differences or odds ratios with 95% CI.Results: A total of 13 studies containing 1,792 patients undergoing TE and 3,068 undergoing PN were identified. Our study showed that the patients received TE had significantly shorter operative time (MD = −28.46, 95% CI = −42.09, −14.83, P < 0.0001), less hospital day (MD = −0.68, 95% CI = −1.04, −0.31, P = 0.0003), less estimate blood loss (MD = −59.90, 95% CI = −93.23, −26.58, P = 0.0004) and smaller change in estimated glomerular filtration rate (fixed effect: MD = 4.66, 95% CI = 1.67, 7.66, P = 0.002), fewer complications (fixed effect: OR = 0.65, 95% CI = 0.50, 0.85, P = 0.001) compared with those received PN. However, there were no significant differences in terms of warm ischemic time, positive margin rates, recurrence rates and survival rates between the two groups. All the subgroup analyses presented consistent results with the overall analyses.Conclusions: Our findings suggested that TE is not only less-traumatizing and beneficial for recovery, but also better for renal function protection. Moreover, it did not show the evidence of an increase relapse rate or mortality rate when compared with PN.

A valid aggregation operator can reflect the decision result more clearly and make the decision effect more correctly. In this article, a linguistic neutrosophic multiset is first proposed to handle the multiplicity information, which is an expanding of neutrosophic multiset. Two Heronian mean operators are proposed to aggregate the linguistic neutrosophic multiset, one is a linguistic neutrosophic multiplicity number generalized-weighted Heronian mean operator, the other is a linguistic neutrosophic multiplicity number improved-generalized-weighted Heronian mean operator, and then their properties are discussed. Furthermore, two decision-making methods are introduced based on linguistic neutrosophic multiplicity number generalized-weighted Heronian mean or linguistic neutrosophic multiplicity number improved-generalized-weighted Heronian mean operators under linguistic neutrosophic multiplicity number environment. Finally, an illustrative example is used to indicate the practicality and validity of these two methods.

In this paper, a novel signal detector based on matrix information geometric dimensionality reduction (DR) is proposed, which is inspired from spectrogram processing. By short time Fourier transform (STFT), the received data are represented as a 2-D high-precision spectrogram, from which we can well judge whether the signal exists. Previous similar studies extracted insufficient information from these spectrograms, resulting in unsatisfactory detection performance especially for complex signal detection task at low signal-noise-ratio (SNR). To this end, we use a global descriptor to extract abundant features, then exploit the advantages of matrix information geometry technique by constructing the high-dimensional features as symmetric positive definite (SPD) matrices. In this case, our task for signal detection becomes a binary classification problem lying on an SPD manifold. Promoting the discrimination of heterogeneous samples through information geometric DR technique that is dedicated to SPD manifold, our proposed detector achieves satisfactory signal detection performance in low SNR cases using the K distribution simulation and the real-life sea clutter data, which can be widely used in the field of signal detection.

Scheidweiler and colleagues have clinically tested and identified a reporting cutoff (10 ng/mL) of nicotine and cotinine in oral fluid that could reliably determine active smoking in patients. The results from that study were reevaluated using a large data set of oral fluid nicotine and cotinine results available from pain medication monitoring. Additionally, test results from patients using a nicotine transdermal patch delivery device are compared with those from smokers. Finally, oral fluid test results collected over a 2-year period were normalized and transformed to yield a near Gaussian distribution for nicotine. The normalized and transformed data reveal the presence of two independent populations: a larger population consistent with active smokers and a smaller population consistent with those passively exposed to smoke. Furthermore, application of this model to patients prescribed transdermal nicotine reveals oral fluid levels consistent with those of active smokers. The clinical delineation of smokers from non-smokers reported earlier is supported by the oral fluid nicotine data modelling presented herein. These data indicate that oral fluid is an acceptable sample matrix for determining the smoking status of patients. Further, these data indicate that oral fluid test results are indistinguishable between patients prescribed transdermal patches and active smokers; however, oral fluid testing can determine absence of patches or smoking. Keywords: Nicotine, Smoking, Transdermal, Cotinine, Oral fluid

In this research, the authors have addressed the collaboration calibration and real-time three-dimensional (3D) localization problem in the multi-view system. The 3D localization method is proposed to fuse the two-dimensional image coordinates from multi-views and provide the 3D space location in real time. It is a fundamental solution to obtain the 3D location of the moving object in the research field of computer vision. Improved common perpendicular centroid algorithm is presented to reduce the side effect of the shadow detection and improve localization accuracy. The collaboration calibration is used to generate the intrinsic and extrinsic parameters of multi-view cameras synchronously. The experimental results show that the algorithm can complete accurate positioning in indoor multi-view monitoring and reduce the complexity.

Background/Aims: The impact of early peritonitis on the outcome of elderly peritoneal dialysis (PD) patients has not been studied. We aimed to research the influence of early peritonitis on patient outcomes in elderly PD patients. Methods: This study involved elderly PD patients (age ≥65) who underwent PD between Jan 1, 2004 and Jul 31, 2013. Patient characteristics were collected in our database. Early peritonitis was defined as peritonitis within 6 months after the initiation of PD. Patient survival and technique were compared among the non-peritonitis, early peritonitis and late peritonitis groups using Cox regression analysis. Results: There were 155 subjects involved in this study. The patients were divided among a non-peritonitis group (n=78), early peritonitis group (n=32) and late peritonitis group (n=45). The organisms causing first peritonitis in the two groups did not differ significantly. After adjustment for age, diabetes, serum albumin and residual renal function, multivariable Cox regression model revealed that compared with the early peritonitis group, both the non-peritonitis group (HR 0.57, RI 0.32-0.99, p=0.046) and the late peritonitis group (HR 0.37, RI 0.16-0.75, p=0.004) exhibited a lower patient mortality rate. Conclusions: Early peritonitis is an independent risk factor for mortality in elderly peritoneal dialysis patients.

Background: To observe the treatment effects of different dialysis modalities on pruritus in elderly uremic patients. Methods: After screening, 67 elderly dialysis patients were selected, including 25 hemodialysis (HD) patients, 20 HD combined with hemodiafiltration (HD + HDF) patients, and 22 peritoneal dialysis (PD) patients. The β2-microglobulin (β2-MG) and intact parathyroid hormone (iPTH) levels were measured before the initial dialysis, and 8 and 12 weeks after the dialysis. During these periods, cutaneous pruritus scores were documented and the remission rate of itching was calculated. Results: There were significant differences in the plasma β2-MG and iPTH levels at 8 and 12 weeks after the initial dialysis in the HDF and PD groups (all p 0.05). After 12 weeks of treatment, the pruritus remission rates in the PD, HDF, and HD groups were 68.18%, 60.00%, and 24.00%, respectively. Conclusion: PD and HDF can clear β2-MG and iPTH and provide relief from cutaneous pruritus efficiently in elderly uremic patients.