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Abstract Objective Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α‐Synuclein (α‐Syn) species in plasma neuron‐derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs). Methods Nanoscale flow cytometry was used to detect α‐Syn‐containing NDEVs in plasma. Results A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α‐Syn, α‐Syn aggregates, and phosphorylated α‐Syn at Ser129 (pS129)‐containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (p

Abstract The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.

Abstract Background In clinical practice, the incidence of hypofibrinogenemia (HF) after tigecycline (TGC) treatment significantly exceeds the probability claimed by drug manufacturers. Objective We aimed to identify the risk factors for TGC-associated HF and develop prediction and survival models for TGC-associated HF and the timing of TGC-associated HF. Methods This single-center retrospective cohort study included 222 patients who were prescribed TGC. First, we used binary logistic regression to screen the independent factors influencing TGC-associated HF, which were used as predictors to train the extreme gradient boosting (XGBoost) model. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were used to evaluate the performance of the model in the verification cohort. Subsequently, we conducted survival analysis using the random survival forest (RSF) algorithm. A consistency index (C-index) was used to evaluate the accuracy of the RSF model in the verification cohort. Results Binary logistic regression identified nine independent factors influencing TGC-associated HF, and the XGBoost model was constructed using these nine predictors. The ROC and calibration curves showed that the model had good discrimination (areas under the ROC curves (AUC) = 0.792 [95% confidence interval (CI), 0.668–0.915]) and calibration ability. In addition, DCA and CICA demonstrated good clinical practicability of this model. Notably, the RSF model showed good accuracy (C-index = 0.746 [95%CI, 0.652–0.820]) in the verification cohort. Stratifying patients treated with TGC based on the RSF model revealed a statistically significant difference in the mean survival time between the low- and high-risk groups. Conclusions The XGBoost model effectively predicts the risk of TGC-associated HF, whereas the RSF model has advantages in risk stratification. These two models have significant clinical practical value, with the potential to reduce the risk of TGC therapy.

Abstract Background The objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China. Methods The prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse. Results A total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P

3D bioprinting technology, a subset of 3D printing technology, is currently witnessing widespread utilization in tissue repair and regeneration endeavors. In particular, light-based 3D bioprinting technology has garnered significant interest and favor. Central to its successful implementation lies the judicious selection of photosensitive polymers. Moreover, by fine-tuning parameters such as light irradiation time, choice of photoinitiators and crosslinkers, and their concentrations, the properties of the scaffolds can be tailored to suit the specific requirements of the targeted tissue repair sites. In this comprehensive review, we provide an overview of commonly utilized bio-inks suitable for light-based 3D bioprinting, delving into the distinctive characteristics of each material. Furthermore, we delineate strategies for bio-ink selection tailored to diverse repair locations, alongside methods for optimizing printing parameters. Ultimately, we present a coherent synthesis aimed at enhancing the practical application of light-based 3D bioprinting technology in tissue engineering, while also addressing current challenges and future prospects.

BackgroundThe latest published therapeutic drug monitoring (TDM) guidelines for vancomycin recommend changing trough-based monitoring to area under the concentration-to-time curve (AUC)-based monitoring. This study aimed to evaluate the implementation status and perceptions of vancomycin AUC-based TDM in China and to determine the challenges in performing AUC-based TDM.MethodsA nationwide cross-sectional survey was conducted in China using an online questionnaire. The questionnaire comprised a total of 25 questions with open- and closed-ended answers to collect information about the current implementation of vancomycin TDM and the participants’ perceptions of these practices. The questionnaire responses were collected via the Questionnaire Star platform and analyzed.ResultsA total of 161 questionnaires were completed by 131 hospitals and were included. Approximately 59.5% (78/131) of the surveyed hospitals conducted vancomycin TDM; however, only 10.7% (14/131) of these hospitals performed AUC-based vancomycin TDM. Of the eligible participants, 58.4% (94/161) had experience with vancomycin TDM, and only 37 participants (37/161, 23.0%) had the ability to estimate the AUC, primarily through Bayesian simulation (33/161, 20.5%). The participants considered the following challenges to implementing AUC-based monitoring: (1) the high cost of AUC-based monitoring; (2) inadequate knowledge among pharmacists and/or physicians; (3) the complexity of AUC calculations; (4) difficulty obtaining AUC software; and (5) unclear benefit of AUC-based monitoring.ConclusionThe majority of surveyed hospitals have not yet implemented AUC-based vancomycin TDM. Multiple challenges should be addressed before wide implementation of AUC-based monitoring, and guidance for trough-based monitoring is still needed.

ABSTRACT: The enclosed multistory poultry housing is a type of poultry enclosure widely used in industrial caged chicken breeding. Accurate identification and detection of the comb and eyes of caged chickens in poultry farms using this type of enclosure can enhance managers’ understanding of the health of caged chickens. However, the accuracy of image detection of caged chickens will be affected by the enclosure's entrance, which will reduce the precision. Therefore, this paper proposes a cage-gate removal algorithm based on big data and deep learning Cyclic Consistent Migration Neural Network (CCMNN). The method achieves automatic elimination and restoration of some key information in the image through the CCMNN network. The Structural Similarity Index Measure (SSIM) between the recovered and original images on the test set is 91.14%. Peak signal-to-noise ratio (PSNR) is 25.34dB. To verify the practicability of the proposed method, the performance of the target detection algorithm is analyzed both before and after applying the CCMNN network in detecting the combs and eyes of caged chickens. Different YOLOv8 detection algorithms, including YOLOv8s, YOLOv8n, YOLOv8m, and YOLOv8x, were used to verify the algorithm proposed in this paper. The experimental results demonstrate that compared to images without CCMNN processing, the precision of comb detection of caged chickens is improved by 11, 11.3, 12.8, and 10.2%. Similarly, the precision of eye detection for caged chickens is improved by 2.4, 10.2, 6.8, and 9%. Therefore, more complete outline images of caged chickens can be obtained using this algorithm and the precision in detecting the comb and eyes of caged chickens can be enhanced. These advancements in the algorithm offer valuable insights for future poultry researchers aiming to deploy enhanced detection equipment, thereby contributing to the accurate assessment of poultry production and farm conditions.

Abstract Background The accumulation of α-synuclein (α-syn), an essential step in PD development and progression, is observed not only in neurons but also in glia, including astrocytes. The mechanisms regulating astrocytic α-syn level and aggregation remain unclear. More recently, it has been demonstrated that a part of α-syn spreading occurs through extracellular vesicles (EVs), although it is unknown whether this process is involved in astrocytes of PD. It is known, however, that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders. Methods Primary astrocytes were transfected with A53T α-syn plasmid or exposed to α-syn aggregates. The level of astrocyte-derived EVs (AEVs) was assessed by nanoparticle tracking analysis and immunofluorescence. The lysosomal function was evaluated by Cathepsin assays, immunofluorescence for levels of Lamp1 and Lamp2, and LysoTracker Red staining. The Apogee assays were optimized to measure the GLT-1+ AEVs in clinical cohorts of 106 PD, 47 multiple system atrophy (MSA), and 103 healthy control (HC) to test the potential of plasma AEVs as a biomarker to differentiate PD from other forms of parkinsonism. Results The number of AEVs significantly increased in primary astrocytes with α-syn deposition. The mechanism of increased AEVs was partially attributed to lysosomal dysfunction. The number of α-syn-carrying AEVs was significantly higher in patients with PD than in HC and MSA. The integrative model combining AEVs with total and aggregated α-syn exhibited efficient diagnostic power in differentiating PD from HC with an AUC of 0.915, and from MSA with an AUC of 0.877. Conclusions Pathological α-syn deposition could increase the astrocytic secretion of EVs, possibly through α-syn-induced lysosomal dysfunction. The α-syn-containing AEVs in the peripheral blood may be an effective biomarker for clinical diagnosis or differential diagnosis of PD.

Background: Elemene injection could provide clinical benefit for the treatment of various cancers, but the clinical evidence is weak. Thus, its wide use in China has raised concerns about the appropriateness of its use.Methods: This was a multicenter retrospective study to evaluate the prevalence of inappropriateness of elemene injection for hospitalized cancer patients. Patients who met the inclusion criteria were retrospectively included, and demographic characteristics were extracted from the hospital information systems. The inappropriateness of elemene injection use was assessed using the preset criteria, and the prevalence was calculated. Multivariate logistic analysis was applied to identify any factors associated with inappropriate use.Results: A total of 275 patients were included in the analysis. The median age was 62 years, and 30.9% were females. The most common cancer was lung cancer (24.0%), and 68.2% of the patients were receiving chemotherapy. The overall prevalence of inappropriateness was 61.8%. The most common reason for inappropriateness was inappropriate indications, and the second was inappropriate doses. Age and oncological department were significant risk factors associated with inappropriate use, while lung cancer, liver cancer and admission to cardiothoracic surgery were associated with a low risk of inappropriate use.Conclusion: The prevalence of inappropriateness among hospitalized elemene injection users was high. More efforts, especially those to improve the appropriateness of indications, should be made to improve the rational use of elemene, as well as other complementary medicines. Physicians should take caution to avoid inappropriate use when prescribing drugs with limited clinical evidence.

Background: Due to the heterogeneity of critically ill patients, the pharmacokinetics of tigecycline are unclear, and the optimal dosing strategy is controversial.Methods: A single-center prospective clinical study that included critically ill patients who received tigecycline was performed. Blood samples were intensively sampled (eight samples each), and plasma drug concentrations were determined. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis and visual predictive checks. Monte Carlo simulation was conducted to optimize the dosage regimen.Results: Overall, 751 observations from 98 patients were included. The final PPK model was a two-compartment model incorporating covariates of creatinine clearance on clearance (CL), body weight on both central and peripheral volumes of distribution (V1 and V2), γ-glutamyl transferase and total bilirubin on intercompartment clearance (Q), and albumin on V2. The typical values of CL, Q, V1 and V2 were 3.09 L/h, 39.7 L/h, 32.1 L and 113 L, respectively. A dosage regimen of 50 mg/12 h was suitable for complicated intra-abdominal infections, but 100 mg/12 h was needed for community-acquired pneumonia, skin and skin structure infections and infections caused by less-susceptive bacteria.Conclusion: The Tigecycline PPK model was successfully developed and validated. Individualized dosing of tigecycline could be beneficial for critically ill patients.

Background: Vancomycin dosing is difficult in critically ill patients receiving continuous renal replacement therapy (CRRT). Previous population pharmacokinetic (PopPK) models seldom consider the effect of residual diuresis, a significant factor of elimination, and thus have poor external utility. This study aimed to build a PopPK model of vancomycin that incorporates daily urine volume to better describe the elimination of vancomycin in these patients.Methods: We performed a multicenter retrospective study that included critically ill patients who received intermittent intravenous vancomycin and CRRT. The PopPK model was developed using the NONMEM program. Goodness-of-fit plots and bootstrap analysis were employed to evaluate the final model. Monte Carlo simulation was performed to explore the optimal dosage regimen with a target area under the curve of ≥400 mg/L h and 400–600 mg/L h.Results: Overall, 113 observations available from 71 patients were included in the PopPK model. The pharmacokinetics could be well illustrated by a one-compartment model with first-order elimination, with the 24-h urine volume as a significant covariate of clearance. The final typical clearance was 1.05 L/h, and the mean volume of distribution was 69.0 L. For patients with anuria or oliguria, a maintenance dosage regimen of 750 mg q12h is recommended.Conclusion: Vancomycin pharmacokinetics in critically ill patients receiving CRRT were well described by the developed PopPK model, which incorporates 24-h urine volume as a covariate. This study will help to better understand vancomycin elimination and benefit precision dosing in these patients.

Perampanel is a promising option for the treatment of pediatric epilepsy, but its plasma concentration varies among patients. This retrospective study aimed to investigate the initial target attainment of perampanel plasma concentration in pediatric patients with epilepsy in China. Inpatients admitted from January 2020 to December 2021 in a tertiary hospital were retrospectively included according to pre-set criteria. Demographic characteristics of patients and dosing strategies and therapeutic drug monitoring results were collected. A total of 137 pediatric patients (84 females and 53 males, aged from 0.6 to 16.4 years) were include for analysis. The perampanel concentrations varied greatly from 60 to 1,560 mg/L among patients, but 89.8% had suitable perampanel concentrations (100–1,000 ng/mL). The concomitant use of enzyme-inductive antiepileptic drugs (AEDs) was the only identified risk factor associated with target nonattainment (OR = 5.92, 95% confidence interval 1.68–20.9). Initial perampanel target attainment in pediatric patients is satisfactory. Routine therapeutic drug monitoring to achieved the suggested concentration range for these patients may be unnecessary, except for those receiving combined enzyme inductive AEDs.

IntroductionThe differentiation between essential tremor (ET) and Parkinson’s disease (PD) can be difficult because of the symptom overlaps. Erythrocytes are the major source of peripheral α-synuclein (α-syn), which is the most studied pathological molecular of PD. We have reported that erythrocytic α-syn levels in PD patients are significantly increased compared to those in healthy controls (HCs). However, little is known about the levels of erythrocytic α-syn species in ET patients.MethodsThis study includes 15 patients with ET, 64 patients with PD, and 49 age and sex matched HCs. A well-established electrochemiluminescence assay was used to measure the erythrocytic total and aggregated α-syn levels. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic values of erythrocytic α-syn for ET diagnosis and differentiation. The correlations of erythrocytic α-syn levels with disease durations were tested using Spearman’s Rank Correlation analysis.ResultsWe found that both erythrocytic total and aggregated α-syn concentrations are significantly increased in PD and ET patients compared to those in HCs. Erythrocytic total α-syn levels are significantly higher in ET patients than those in PD group. Furthermore, the ratios of erythrocytic aggregated to total α-syn levels in ET patients are significantly decreased than those in PD and HC subjects. We also found a significant association of erythrocytic aggregated α-syn levels with the disease duration of ET patients.ConclusionOur findings suggest new insight into the changes of erythrocytic total and aggregated α-syn levels as potential biomarkers for ET patients.

ABSTRACT: Objective: We conducted this multicenter retrospective study to evaluate the prevalence, clinical patterns, and risk factors for tigecycline-induced liver injury, which is a type of drug-induced liver injury (DILI). Methods: Inpatients receiving intravenous tigecycline for ≥7 days were included. Patient information was collected to assess possible DILIs. The pattern and severity of tigecycline DILI were evaluated. A multivariable logistic regression model was used to identify the independent risk factors associated with tigecycline DILI. Results: A total of 986 patients were identified and 397 patients were included in this study. The prevalence of tigecycline DILI was 10.3% (95% confidence interval [CI] = 7.51–13.7%). The most common type of tigecycline DILI was cholestatic, with mild severity observed in most cases. Abnormal baseline alanine aminotransferase levels (odds ratio [OR] = 3.11, 95% CI = 1.55–6.24, P = 0.001), intensive care unit admission (OR = 2.63, 95% CI = 1.32–5.36, P = 0.006), and treatment length (in weeks) (OR = 1.25, 95% CI = 1.05–1.49, P = 0.011) were independent risk factors for tigecycline DILI. Conclusion: Our results indicate that the prevalence of tigecycline DILI is high, and that the patients at risk should receive special attention.

BackgroundCortical amyloid deposition is a common observation in Parkinson’s disease dementia (PDD) patients. Aβ1-42 is linked to a more rapid progression of dementia. Platelets, which degranulate upon activation, are a primary source of Aβ. It has been repeatedly reported that peripheral extracellular vesicles (EVs) can partially reach the central nervous system. Thus, we speculate that activated platelet-derived Aβ1-42-containing EVs (PEV-Aβ1-42) play a crucial role in the cognitive decline of PD patients.MethodsThe study included 189 participants: 66 with non-dementia PD, 73 with PDD, and 50 healthy controls. All participants underwent blood collection and clinical assessments. Twenty PD patients underwent re-examination and repeated blood collection 14 months later. A nano-scale flow cytometry assay was used to detect PEVs and PEV-Aβ1-42 using fluorescence-labeled CD62P and Aβ1-42 antibodies.ResultsParkinson’s disease dementia patients had higher PEV-Aβ1-42 concentrations than healthy controls (p = 0.028). The ratio of PEV-Aβ1-42 to PEV was significantly higher in PDD patients compared to those in non-dementia PD and healthy controls (pPD-ND

Abstract Background Immune system dysfunction, including higher levels of peripheral monocytes and inflammatory cytokines, is an important feature of Parkinson’s disease (PD) pathogenesis, although the mechanism underlying the process remains to be investigated. In the central nervous system, it is well-known that α-synuclein (α-syn), a key protein involved in PD, activates microglia potently, and it is also reported that α-syn exists in the peripheral system, especially in erythrocytes or red blood cells (RBC) at exceedingly high concentration. The current study focused on the possibility that RBC-derived α-syn mediates the sensitization of peripheral monocytes in PD patients. Methods The hyperactivation of monocytes was assessed quantitatively by measuring mRNA levels of typical inflammatory cytokines (including IL-1β, IL-6 and TNF-α) and protein levels of secreted inflammatory cytokines (including pro-inflammatory cytokines: IL-1β, IL-6, TNF-α, IL-8, IFN-γ, IL-2, and IL-12p70 and anti-inflammatory cytokines: IL-4, IL-10, and IL-13). Western blot, nanoparticle tracking analysis and electron microscopy were used to characterize RBC-derived extracellular vesicles (RBC-EVs). Inhibitors of endocytosis and leucine-rich repeat kinase 2 (LRRK2), another key protein involved in PD, were used to investigate how these two factors mediated the process of monocyte sensitization by RBC-EVs. Results Increased inflammatory sensitization of monocytes was observed in PD patients and PD model mice. We found that α-syn-containing RBC-EVs isolated from PD model mice or free form oligomeric α-syn induced the inflammatory sensitization of THP-1 cells, and demonstrated that endocytosis was a requirement for this pathophysiological pathway. Furthermore, the hyperactivation of THP-1 cells induced by RBC-EVs was associated with increased LRRK2 production and kinase activity. The phenomenon of inflammatory sensitization of human monocytes and increased LRRK2 were also observed by the treatment of RBC-EVs isolated from PD patients. Conclusions Our data provided new insight into how hyperactivation of monocytes occurs in PD patients, and identified the central role played by α-syn-containing RBC-EVs in this process.

Abstract With excellent electrical conductivity, fluidity, rheological property, and biocompatibility, gallium has been intensively studied in the fields of flexible electronics and devices, thermal management, and soft robotics. However, the large degree of supercooling of gallium presents a large limitation for phase transition‐related applications such as the very low temperature required for solidification, the impurities, and side effects brought in by nucleating agents. In this study, solidification process of liquid gallium by using solid gallium as a nucleating agent is discovered to be fast and facile at room temperature compared with other agent materials including copper, iron, and nickel. Quantificationally, solidified gallium as a nucleating agent, can effectively reduce the supercooling degree from about 66.3 to 14.8 °C. The freezing velocity can reach to 200 mm3 min−1. The possible mechanism is reducing the energy barrier via adding nucleation site, allowing rapid solidification at room temperature accompanying heat dissipation. Moreover, micromechanical properties are compared between raw solid Ga and the solidified Ga induced by Ga agent, which suggests a slight decrease in mechanical strength at room temperature with the nucleating agent. It will be beneficial to understand the phase change and also provide guidance for the application of gallium regarding its mechanical properties.

Cryptotanshinone (CTS) is a plant product extracted from Salvia miltiorrhiza Bunge with various pharmacological significances. In addition to its activities against coronary heart disease, hyperlipidemia, stroke, hepatitis and chronic renal failure, it demonstrates antimetastatic effects. However, its clinical use is limited due to its poor aqueous solubility and oral bioavailability. Herein, CTS nanocrystals were prepared with the precipitation method followed by high-pressure homogenization using Poloxamer 407 as the stabilizer. A stable product was further obtained by lyophilization. The particle size of the CTS nanocrystals was 315.67 ± 11.02 nm, and the zeta potential was near 0 mV. The crystallinity was confirmed by DSC and PXRD. The saturation solubility was substantially increased from 0.97 ± 0.12 μg/ml to 62.29 ± 1.91 μg/ml, and the dissolution rate was also significantly accelerated. A pharmacokinetic study in rats revealed an improvement in oral bioavailability (2.87-fold) with CTS nanocrystals compared to the raw drug. In conclusion, the results of this study suggest a feasible formulation for the oral delivery of CTS.

The way in which information is linguistically presented can impact audience attention, emotion, and cognitive responses, even if the content remains unchanged. The present study aims to examine the effects of rhetorical devices on audience responses by introducing a new theoretical framework, the augmented elaboration likelihood model (A-ELM), which integrates elements of the Elaboration Likelihood Model and narrative theory. The results show that the mediation effects of attention on the relationships between rhetorical devices and affective and cognitive elaborations are moderated by involvement. Nonnarrative evidence, combined narrative and numerical evidence, source credibility, and tropes versus the lack of figures of speech, elicit better audience responses in low-involvement situations, whereas numerical evidence outperforms narratives in high-involvement situations. This study not only offers a novel theoretical framework in the form of A-ELM, but also has important implications for advancing methodologies and practical applications.

The realization of the liquid metal heartbeat effect shows better controllability under non-periodic stimuli than spontaneous oscillation or periodic stimuli. However, adjusting the liquid metal heartbeat performance, drop spreading area, and frequency, solely by the magnitude of the voltage, has great limitations. Here, we demonstrate that the eGaIn drop can beat inside graphite ring electrodes under DC voltage in alkaline solutions on ratchet substrates. These sawtooth structures provide asymmetric textures which influence liquid metal deformation during the beating of the heart. We achieved heartbeat frequencies from 2.7 to 4.8 Hz, a 100% increase in the tunable frequency range compared to that on a flat surface. The oxidative spreading of the eGaIn drop on the ratchet substrate shows that the drop penetrates into the grooves of the sawtooth structure. Moreover, we investigated the physical mechanisms affecting the eGaIn heartbeat frequency and the influence on the spreading area of the eGaIn drop at various sawtooth sizes and orientations. These findings not only enhance our understanding of droplet manipulation on sawtooth-structured surfaces but also facilitate the design of microfluidic pump systems.

Heat stress is one of the most important environmental stressors facing poultry production. The presence of heat stress will reduce the antioxidant capacity and immunity of poultry, thereby seriously affecting the health and performance of poultry. The paper proposes an improved FPN-DenseNet-SOLO model for poultry heat stress state detection. The model uses Efficient Channel Attention (ECA) and DropBlock regularization to optimize the DenseNet-169 network to enhance the extraction of poultry heat stress features and suppress the extraction of invalid background features. The model takes the SOLOv2 model as the main frame, and uses the optimized DenseNet-169 as the backbone network to integrate the Feature Pyramid Network to detect and segment instances on the semantic branch and mask branch. In the validation phase, the performance of FPN-DenseNet-SOLO was tested with a test set consisting of 12,740 images of poultry heat stress and normal state, and it was compared with commonly used object detection models (Mask R CNN, Faster RCNN and SOLOv2 model). The results showed that when the DenseNet-169 network lacked the ECA module and the DropBlock regularization module, the original model recognition accuracy was 0.884; when the ECA module was introduced, the model's recognition accuracy improved to 0.919. Not only that, the recall, AP0.5, AP0.75 and mean average precision of the FPN-DenseNet-SOLO model on the test set were all higher than other networks. The recall is 0.954, which is 15, 8.8, and 4.2% higher than the recall of Mask R CNN, Faster R CNN and SOLOv2, respectively. Therefore, the study can achieve accurate segmentation of poultry under normal and heat stress conditions, and provide technical support for the precise breeding of poultry.

Introduction: Polymyxin B is a last-line therapy for carbapenem-resistant microorganisms. However, a lack of clinical pharmacokinetic/pharmacodynamic (PK/PD) data has substantially hindered dose optimization and breakpoint setting.Methods: A prospective, multi-center clinical trial was undertaken with polymyxin B [2.5 mg/kg loading dose (3-h infusion), 1.25 mg/kg/12 h maintenance dose (2-h infusion)] for treatment of carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI). Safety, clinical and microbiological efficacy were evaluated. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to determine the concentrations of polymyxin B in blood samples. Population pharmacokinetic (PK) modeling and Monte Carlo simulations were conducted to examine the susceptibility breakpoint for polymyxin B against BSI caused by CRKP.Results: Nine patients were enrolled and evaluated for safety. Neurotoxicity (5/9), nephrotoxicity (5/9), and hyperpigmentation (1/9) were recorded. Blood cultures were negative within 3 days of commencing therapy in all 8 patients evaluated for microbiological efficacy, and clinical cure or improvement occurred in 6 of 8 patients. Cmax and Cmin following the loading dose were 5.53 ± 1.80 and 1.62 ± 0.41 mg/L, respectively. With maintenance dosing, AUCss,24 h was 79.6 ± 25.0 mg h/L and Css,avg 3.35 ± 1.06 mg/L. Monte Carlo simulations indicated that a 1 mg/kg/12-hourly maintenance dose could achieve >90% probability of target attainment (PTA) for isolates with minimum inhibitory concentration (MIC) ≤1 mg/L. PTA dropped substantially for MICs ≥2 mg/L, even with a maximally recommended daily dose of 1.5 mg/kg/12-hourly.Conclusion: This is the first clinical PK/PD study evaluating polymyxin B for BSI. These results will assist to optimize polymyxin B therapy and establish its breakpoints for CRKP BSI.

A deep learning model named Cracklab for pixel level segmentation and measurement of concrete cracks is proposed. Cracklab excels at handling cracks at image edges and enhances scale adaptability, and it reduces physical occupation and increases efficiency by pruning. A crack database containing 685 images collected from complex scenes is established, with resolution ranging from 1024 to 2048 pixels. During training, focal loss is used to improve the recognition effect of complex background images. The results show that our method is more effective and accurate in detecting and quantifying cracks. Cracklab performed better in inference and comparative experiments, with mIoU at least 0.114 ahead and detection speeds 3.9 times faster compared to works that did not include pruning and scale adaptation. The proposed improved medial axis transform method has an error of 2.09 pixels at the maximum crack width, which is 19.6% lower than another work using distance transform method.

BackgroundThe definitive diagnosis of Multiple system atrophy (MSA) requires the evidence of abnormal deposition of α-Synuclein (α-Syn) through brain pathology which is unable to achieve in vivo. Deposition of α-Syn is not limited to the central nervous system (CNS), but also extended to peripheral tissues. Detection of pathological α-Syn deposition in extracerebral tissues also contributes to the diagnosis of MSA. We recently reported the increased expressions of α-Syn, phosphorylated α-Synuclein at Ser129 (pS129), and α-Syn aggregates in oral mucosal cells of Parkinson’s disease (PD), which serve as potential biomarkers for PD. To date, little is known about the α-Syn expression pattern in oral mucosa of MSA which is also a synucleinopathy. Here, we intend to investigate whether abnormal α-Syn deposition occurs in oral mucosal cells of MSA, and to determine whether α-Syn, pS129, and α-Syn aggregates in oral mucosa are potential biomarkers for MSA.MethodsThe oral mucosal cells were collected by using cytobrush from 42 MSA patients (23 MSA-P and 19 MSA-C) and 47 age-matched healthy controls (HCs). Immunofluorescence analysis was used to investigate the presence of α-Syn, pS129, and α-Syn aggregates in the oral mucosal cells. Then, the concentrations of α-Syn species in oral mucosa samples were measured using electrochemiluminescence assays.ResultsImmunofluorescence images indicated elevated α-Syn, pS129, and α-Syn aggregates levels in oral mucosal cells of MSA than HCs. The concentrations of three α-Syn species were significantly higher in oral mucosal cells of MSA than HCs (α-Syn, p

Since the beginning of 2016, China’s annual emissions of herbal residues (HR) have exceeded 30 million tons. As a kind of solid waste, HR still contains a large amount of organic matter, which requires further industrial extraction procedure. Most of the existing studies are concerned with the feasibility of utilizing traditional Chinese medicine residues, meanwhile there are very few studies regarding the kinetics of pyrolysis in the process of resource utilization of traditional Chinese medicine residues. In this study, we comprehensively studied the kinetics characteristics of raw materials with various heating rates (10, 20, 30, and 40°C/min) using a synchronous thermogravimetric analysis, and we adopted Coats-Redfern model to study the thermal kinetics and thermal analysis of GBR. A novel method combining Genetic algorithm and Adaboost algorithm (GA-Adaboost) is proposed to predict the thermogravimetric curve of the raw plant material with respect to the heating rate and temperature. The experimental result shows that the activation energy of the raw material was determined by the Kissinger-Akahira-Sunose (KAS) (E=148.71kJ/mol), and the correlation coefficient was greater than 0.99. The optimal reaction mechanism determined by the Coats - Redfern method was random nucleation and subsequent growth. The GA-Adaboost model achieved good performance (with a fitting degree of 99.88% on training data, 99.80% on verification data, and MSE of3.4173) while predicting the pyrolysis process of ginkgo biloba residue. This study will provide theoretical basis and technical support for the efficient resource utilization of pharmaceutical residues and reduce environmental pressure.

Abstract Allergic reactions are common reasons for withdrawal of oxcarbazepine treatment in patients with epilepsy. However, some patients are not responsive to other antiseizure medications. Herein, two pediatric patients with epilepsy and allergic to oxcarbazepine to whom oxcarbazepine therapy was successfully reintroduced are described. The reintroduction strategy used in this study was simple, feasible, and suitable for the reintroduction of oxcarbazepine in pediatric patients with epilepsy.

ObjectiveThe objective of this study was to assess the status and trends of antiviral treatment in outpatients with herpes zoster in China.MethodsPrescription data on antiviral drugs were extracted from the database of the Hospital Prescription Analysis Program of China according to the inclusion criteria. Yearly prescriptions and costs were calculated, and trends were analyzed. The trends were further stratified by age, sex, and specific drug use. The distribution of defined daily costs (DDCs) of valaciclovir and famciclovir were analyzed, and trends in the median DDCs were identified.ResultsA total of 132,911 prescriptions from 49 hospitals located in six major areas of China were included in the analysis. The yearly prescriptions containing antivirals increased from 8,819 in 2010 to 16,361 in 2019. The percentage of prescriptions for patients aged 65 years and above also increased (27.7% in 2010 to 31.0% in 2019), and the number of prescriptions for females was higher than those for males (P < 0.001). The average cost of antivirals per prescription decreased; thus, the yearly cost showed no increasing trend. The main prescribed antivirals were valaciclovir and famciclovir, which progressively increased in prescriptions. The use of acyclovir decreased during the study period. Prescriptions containing topical formulations, acyclovir and penciclovir, both increased. The DDCs of valaciclovir and famciclovir decreased dramatically.ConclusionThe use of antivirals has increased over the decade, while the cost has not. Antiviral treatments adhere well to recent recommendations, except for the use of topical antivirals. The findings of this study may benefit the healthcare source allocation and management of herpes zoster in China.

Background:The inappropriate use of pharmacological treatments for insomnia may increase patients' risk of serious adverse events. However, few epidemiological studies on the use of medications for insomnia in China have been conducted to date.ObjectiveWe aimed to investigate the current pharmacological treatments for insomnia and guide the rational use of drugs.MethodsThe prescription data of outpatients with insomnia between 2015 and 2019 in Zhejiang province were extracted from the Hospital Prescription Analysis Cooperative Project of China and evaluated. The demographic characteristics of insomnia and the proportion and prescription trends of different drugs were analyzed along with multidrug combinations for insomnia.ResultsThe number of patients with insomnia who were prescribed medications for insomnia increased from 2,385 in 2015 to 3,919 in 2019, with an increase of 64.32%, whereas the mean age of these patients decreased from 64.07 years to 60.94 years. There were nearly 1.42 times as many female patients prescribed medications for insomnia as male patients, and female patients tended to be younger than male patients. Benzodiazepines (53.99%) were the most common type of medicine for insomnia. The incidence of benzodiazepine usage decreased significantly yearly (P < 0.01), whereas the incidences of non-benzodiazepine receptor agonist (nBZRA) and antidepressant usage increased (P < 0.05). The most common benzodiazepine, nBZRA, antidepressant, and antipsychotic were estazolam, zolpidem, trazodone, and olanzapine, respectively. A total of 13.97% of outpatients with insomnia were prescribed multiple drugs for insomnia, even though nearly half of the drug combinations had similar pharmacological mechanisms.ConclusionsBenzodiazepines remained the most common medication for insomnia, but the prescription rates of nBZRAs and antidepressants increased. Attention should be paid to multidrug combinations for insomnia, which may lead to an increased risk of serious adverse effects.

The aim of this study was to assess the patterns and trends of pharmacological treatment for outpatients with postherpetic neuralgia (PHN) in China in the period 2015–2019. Prescription data for outpatients with PHN were extracted from the database of the Hospital Prescription Analysis Program of China according to the inclusion criteria. The trends in yearly prescriptions and corresponding costs were analyzed and stratified by drug class and specific drugs. A total of 19,196 prescriptions from 49 hospitals in 6 major regions of China were included for analysis. The yearly prescriptions increased from 2534 in 2015 to 5676 in 2019 (p = 0.027), and the corresponding expenditures increased from CNY 898,618 in 2015 to CNY 2,466,238 in 2019 (p = 0.027). Gabapentin and pregabalin are the most commonly used drugs for PHN, and more than 30% of these two drugs were combined with mecobalamin. Opioids were the second most frequently prescribed drug class, and oxycodone accounted for the largest share of the cost. Topical drugs and TCAs are rarely used. The frequent use of pregabalin and gabapentin was in accordance with current guidelines; however, the use of oxycodone raised concerns about rationality and economic burden. The results of this study may benefit the allocation of medical resources and management for PHN in China and other countries.

BackgroundPathological α-synuclein (α-Syn) is not only exclusive to the central nervous system (CNS) in Parkinson’s disease (PD), but also extended to biofluids and peripheral tissues including oral cavity. Both oral mucosa and nervous system are derived from ectodermal tissue, and potentially share common disease-specific characteristics. Oral mucosal exfoliative cytology is a non-invasive technique, which is an easily acceptable for patients and ordinary people. The purpose of this study was to determine the abnormal accumulation of α-Syn in oral mucosa of PD patients and to learn the diagnostic utility of oral mucosa α-Syn for PD.MethodsThe oral mucosa samples were obtained from 57 patients with PD and 51 age-matched controls by cytological brush. Immunofluorescence analysis was used to investigate the presence and subcellular localization of α-Syn, phosphorylated α-Syn at Ser129 (pS129) and oligomeric α-Syn in the oral mucosa cells of PD patients and controls. Images taken as Z-stacks were analyzed for 3D reconstruction to visualize the α-Syn intracellular localization. Then, the concentrations of α-Syn, pS129, and oligomeric α-Syn in oral mucosa samples were measured using electrochemiluminescence assays.ResultsImmunofluorescence images revealed the increased α-Syn, pS129, and oligomeric α-Syn levels in oral mucosa cells of PD patients than age-matched controls. The intracellular distributions of α-Syn species were determine by Z-stack images with 3D reconstruction, and α-Syn was detected in both the nucleus and cytoplasm. However, pS129 was mainly located in the cytoplasm, and oligomeric α-Syn was highly expressed in the nucleus and perinuclear cytoplasm. The concentrations of three α-Syn species were significantly increased in the oral mucosa cell samples of PD patients than controls (α-Syn, p = 0.001; pS129, p = 0.002; oligomeric α-Syn, p = 0.013). In PD patients, the oral mucosa α-Syn and oligomeric α-Syn levels were significantly correlated with Hoehn-Yahr scales (α-Syn, r = 0.495, p = 0.001; oligomeric α-Syn, r = 0.324, p = 0.03). The area under curve (AUC) of ROC analysis using an integrative model including α-Syn, pS129, and oligomeric α-Syn for PD diagnosis was 0.749, with 66.7% sensitivity and 72.5% specificity.ConclusionThis study for the first time demonstrated increased expressions of α-Syn, pS129, and oligomeric α-Syn in oral mucosa cells from PD patients, which serve as useful and non-invasive PD diagnostic biomarkers.

Abstract Background The introduction of non-VKA oral anticoagulants (NOACs) has changed the landscape of preventing thromboembolism events in many countries. However, the prescription trends of oral anticoagulant (OAC) in China are still unclear, which were evaluated in this study through data extracted and summarized from 5 major cities as representatives. Methods This study was designed as a time-series study which was based on pharmacy prescription data. Analysis was performed on yearly aggregated visits and expenditure. The results were also stratified by indications and specialties. Results A total of 189,006 prescriptions of 67 hospitals in 6 years were included in the study. The average growth rates of overall visit and expenditure of OAC were 15.8 and 57.5%, respectively. The share of warfarin decreased and NOACs had taken 92% of cost, covering 28% of patients in 2017. The more frequently used NOACs were rivaroxaban and dabigatran. The use of OAC was differed by indication and specialty. Conclusion The use of NOACs was found increasing rapidly in both visits and cost, sharing a majority of cost with a minority of patients. Attentions should be paid on the rational use of NOACs.

BackgroundErythrocytes contain most of the peripheral α-synuclein (α-syn), which is the key pathological molecular of α-synucleinopathies including Parkinson’s disease (PD). Our objectives were to assess the efficiency of erythrocytic total and oligomeric α-syn levels as PD diagnostic biomarkers, and to identify the correlations between erythrocytic α-syn levels and physiological/psychiatrical assessment scales.MethodsHome-brewed electrochemiluminescence assays were applied to assess the concentrations of erythrocytic total and oligomeric α-syn levels in a cohort including 124 patients with PD and 79 healthy controls (HCs). The correlations between erythrocytic α-syn levels and clinical measurements were assessed using Spearman’s rank test.ResultsBoth the erythrocytic total and oligomeric α-syn levels were significantly higher in PD patients than HCs. The biomarkers adjusted for age and sex discriminated PDs from HCs well with 80% sensitivity, 89% specificity and 79% sensitivity, 83% specificity, respectively. Combining erythrocytic total and oligomeric α-syn levels by using binary logistic regression analysis with the controlling of age and sex generated a factor discriminates PDs from HCs with 88% sensitivity and 85% specificity. The erythrocytic total but not oligomeric α-syn levels adjusted for age and sex significantly correlated with anxiety scales and the MDS-UPDRS III scales in PD patients, respectively.ConclusionWe showed the usefulness of erythrocytic total and oligomeric α-syn levels as biomarkers for PD. Our results also suggest the capability of erythrocytic α-syn as a potential pathological factor and therapeutic target for psychiatric symptoms in PD patients.

ObjectiveThe use of attention-deficit hyperactivity disorder (ADHD) medication is increasing worldwide, but its status in China is unknown. This research aimed to assess the trends of ADHD medication use in young Chinese patients between 2010 and 2019.MethodsDispensing data related to ADHD medication use were extracted from the Hospital Prescription Analysis Cooperative Project of China. The trends in the yearly prescription number of ADHD drugs and corresponding cost were analyzed. We further stratified the data by age, sex, and specific drug.ResultsFrom 2010 to 2019, sampled prescriptions for ADHD medication increased from 902 to 4531, and the total expenditure increased rapidly from 276,580 to 2,412,308 Chinese Yuan. Prescriptions for males were almost fourfold more than that for females. Patients aged 6–11 years had the highest number of prescriptions for ADHD medication each year, accounting for more than 50% of the total number of prescriptions. The percentage of methylphenidate prescriptions decreased from 91.9% in 2010 to 76.9% in 2019, and the corresponding cost declined from 77.3% to 66.8%. In contrast, atomoxetine prescriptions increased progressively and accounted for about 24.5% of the total prescriptions at the end of the study.ConclusionsThe use of ADHD drugs and the corresponding cost increased rapidly in China, and methylphenidate was the most frequently prescribed medicine. The increase in ADHD prescriptions requires attention to ensure that it reflects appropriate use, especially in patients aged 6–11 years.

Concrete cracks have always been the focus of research because of the serious damage they cause to structures. With the updating of hardware and algorithms, the detection of concrete structure surface cracks based on computer vision has received extensive attention. This paper proposes an improved algorithm based on the open-source model Deeplabv3+ and names it Deeplabv3+ BDF according to the optimization strategy used. Deeplabv3+ BDF first replaces the original backbone Xception with MobileNetv2 and further replaces all standard convolutions with depthwise separable convolutions (DSC) to achieve a light weight. The feature map of a shallow convolution layer is additionally fused to improve the detail segmentation effect. A new strategy is proposed, which is different from the two-stage training. The model training is carried out in the order of transfer learning, coarse-annotation training and fine-annotation training. The comparative test results show that Deeplabv3+ BDF showed good performance in the validation set and achieved the highest mIoU and detection efficiency, reaching real-time and accurate detection.

The prevalence of dry eye disease (DED) in old patients are high, corresponding to a substantial economic burden. In this cross-sectional study, we analyzed the trends in the topical prescriptional treatment of old patients with DED in six major areas of China. Information on topical drug prescriptions for DED patients aged above 60 years was extracted from the Hospital Prescription Analysis Cooperative Program of China database. Trends in yearly prescriptions and cost were analyzed. The data were further stratified by patient age and sex, drug class, and specific drug. A total of 130,734 prescriptions from 52 hospitals located in six major areas of China were analyzed. The number of prescripptions per year for patients with DED increased from 13,308 in 2013 to 22,074 in 2019, with a corresponding increase in cost of all topical drugs from 1,490,014 Chinese Yuan (CNY) to 2,618,206 CNY. Drugs for the treatment of DED accounted for the largest proportion of the total cost in each year. Ocular lubricants were the main pharmacotherapy agent. Sodium hyaluronate use increased over time, and the drug was used by 65.9% of patients by the end of the study. Pranoprofen was the second most frequently used drug. The most frequently used drugs for co-incident disease were antimicrobials. Treatment patterns for DED haven’t changed, and the most frequently used drug combination was sodium hyaluronate and pranoprofen. In summary, prescription for old patients with DED and the cost of treatment are increasing. Ocular lubricants are the main treatment option, while sodium hyaluronate is the most frequently used drug. The observed trends can lead to more efficient allocation of health care resources in China.

Abstract Aramid fibers are widely used in many cutting‐edge fields, including space, aviation, military, and electronics. However, their poor UV resistance and surface inertness seriously hinder their utilization, especially in harsh environments. Here, a dual‐layer ultrathin Al2O3–TiO2 coating with a thickness of 70–180 nm is fabricated on aramid fibers by a modified atomic layer deposition (ALD) method. The tenacity of ALD‐coated aramid fibers decreases only by ≈0.85% after exposure to intense UV light (4260 W m−2) under high temperature (>200 ℃) for 90 min, which equals to continuous exposure to sunlight for about 17 500 days. The as‐prepared aramid fibers also show excellent laundering durability, thermal and chemical stabilities. This work presents a green and damage‐free approach to achieve the highly anti‐UV aramid fibers without sacrificing their outstanding performance, which is expected to guide material design for future innovations in functional fibers and devices.

Existing push robots mainly use magnetic induction technology. These devices are susceptible to external electromagnetic interference and have a low degree of intelligence. To make up for the insufficiency of the existing material pushing robots, and at the same time solve the problems of labor-intensive, labor-intensive, and inability to push material in time at night, etc., in this study, an autonomous navigation pusher robot based on 3D lidar is designed, and an obstacle avoidance strategy based on the improved artificial potential field method is proposed. Firstly, the 3D point cloud data of the barn is collected by the self-designed pushing robot, the point cloud data of the area of interest is extracted using a direct-pass filtering algorithm, and the 3D point cloud of the barn is segmented using a height threshold. Secondly, the Least-Squares Method (LSM) and Random Sample Consensus (RANSAC) were used to extract fence lines, and then the boundary contour features were extracted by projection onto the ground. Finally, a target influence factor is added to the repulsive potential field function to determine the principle of optimal selection of the parameters of the improved artificial potential field method and the repulsive direction, and to clarify the optimal obstacle avoidance strategy for the pusher robot. It can verify the obstacle avoidance effect of the improved algorithm. The experimental results showed that under three different environments: no noise, Gaussian noise, and artificial noise, the fence lines were extracted using RANSAC. Taking the change in the slope as an indicator, the obtained results were about −0.058, 0.058, and −0.061, respectively. The slope obtained by the RANSAC method has less variation compared to the no-noise group. Compared with LSM, the extraction results did not change significantly, indicating that RANSAC has a certain resistance to various noises, but RANSAC performs better in extraction effect and real-time performance. The simulation and actual test results show that the improved artificial potential field method can select reasonable parameters and repulsive force directions. The optimized path increases the shortest distance of the obstacle point cloud from the navigation path from 0.18 to 0.41 m, where the average time is 0.059 s, and the standard deviation is 0.007 s. This shows that the optimization method can optimize the path in real time to avoid obstacles, basically meet the requirements of security and real-time performance, and effectively avoid the local minimum problem. This research will provide corresponding technical references for pusher robots to overcome the problems existing in the process of autonomous navigation and pushing operation in complex open scenarios.

The pushing robot working in the complex farming environment encounters several problems. For example, the precision of its navigation path extraction is low, and its working quality is greatly affected by the weather. In view of this, a method of farm operation path extraction based on machine vision is proposed in this study in order to solve the problems above and realize the autonomous and intelligent operation of the robot. First of all, the RGB images of the working area in front of the robot are obtained by using an RGB camera installed on the machine. Then, the collected images are preprocessed by means of sky removal, denoising and grayscale transformation. After that, the image is segmented to obtain the front fence, feed belt and ground data. Finally, the navigation path is obtained by extracting the features of the feed belt. The test results show that the absolute deviation of the pushing robot at different initial lateral distances is less than ±15 cm, and the deviation between the actual navigation route and the target route is within the expected range. The absolute value of the maximum lateral deviation in five test areas is 8.9 cm, and the absolute value of the average maximum lateral deviation is 7.6 cm. These experimental results show that the pushing robot can work stably without disturbing the feeding of cows. Particle swarm optimization is used to optimize the parameters of the PID and find the optimal parameters. This makes the system balanced and more responsive. Through this test, it is found that the initial direction of the robot will have a certain impact on the path production and tracking efficiency, and this effect is more significant when the robot changes the working area or turns. In which case, the trajectory of the robot should be in such a way that it immediately faces the next row at a small angular deviation, thus ensuring smoother motion. The method proposed in this study can provide support for the automatic navigation of pushing robots in dairy farms.

This study aimed to assess the national trends in anti-seizure medication (ASM) prescription in Chinese adult outpatients with epilepsy over a 6-year period from 2013 to 2018. Prescriptions for adult outpatients with epilepsy from hospitals in six major cities were extracted from the database of the Hospital Prescription Analysis Cooperative Project. Trends in the annual prescriptions and expenditure of ASM were analyzed. Prescription patterns (monotherapy or combination therapy) were also assessed. A total of 225,767 prescriptions from 60 hospitals were eligible and extracted for analysis. The number of ASM prescriptions increased from 28,360 in 2013 to 44,110 in 2018, and the corresponding cost increased from 9,452,990 Chinese Yuan (CNY) in 2013 to 14,627,865 CNY in 2018. The share of newer ASM use increased continuously, accounting for 56.75% of prescriptions and 85.03% of expenditure in 2018. The most frequently prescribed ASMs were sodium valproate and levetiracetam. The proportion of sodium valproate use decreased, while the proportion of levetiracetam use increased dramatically in terms of both ASM prescriptions and expenditure. Monotherapy was more frequent than combination therapy. The three most common combination therapies were sodium valproate/lamotrigine, levetiracetam/oxcarbazepine, and sodium valproate/levetiracetam. In summary, ASM use increased rapidly in terms of the number of ASM prescriptions and cost during the 6-year period, which raises concern regarding the rational use and pharma-economic profiles of ASMs. In place of valproate, levetiracetam became the most frequently used ASM. The development of ASM prescription is in line with therapy guidelines and reflects the current state of research in China.

Summary: Nature-inspired superamphiphilic surfaces have drawn tremendous attention owing to its extreme liquid-loving behaviors. Herein, a micro-organized nano-channel (Mo-Na) superamphiphilic anodic aluminum oxide (AAO) surface with long-lasting superamphiphilic property is prepared by a facile one-step anodization method with controllable temperature change. Analysis of dynamic wetting behaviors on superamphiphilic Mo-Na AAO surfaces for various liquids reveals that the spreading factor is in negative correlation with the surface tension and liquid polarity. Detailed observation of the three-phase contact line shows a micro-scale capillary film on superamphiphilic Mo-Na AAO surfaces, which results from the horizontal component of the capillary force. Taking advantage of the superamphiphilic property, water droplets can spread completely on these Mo-Na AAO surfaces within a short time, which can be applied for efficient heat dissipation. Moreover, the unique AAO surface with Mo-Na structures also offers an effective template for future efforts in AAO-based composite devices.

The feeding behaviour of cows is an essential sign of their health in dairy farming. For the impression of cow health status, precise and quick assessment of cow feeding behaviour is critical. This research presents a method for monitoring dairy cow feeding behaviour utilizing edge computing and deep learning algorithms based on the characteristics of dairy cow feeding behaviour. Images of cow feeding behaviour were captured and processed in real time using an edge computing device. A DenseResNet-You Only Look Once (DRN-YOLO) deep learning method was presented to address the difficulties of existing cow feeding behaviour detection algorithms’ low accuracy and sensitivity to the open farm environment. The deep learning and feature extraction enhancement of the model was improved by replacing the CSPDarknet backbone network with the self-designed DRNet backbone network based on the YOLOv4 algorithm using multiple feature scales and the Spatial Pyramid Pooling (SPP) structure to enrich the scale semantic feature interactions, finally achieving the recognition of cow feeding behaviour in the farm feeding environment. The experimental results showed that DRN-YOLO improved the accuracy, recall, and mAP by 1.70%, 1.82%, and 0.97%, respectively, compared to YOLOv4. The research results can effectively solve the problems of low recognition accuracy and insufficient feature extraction in the analysis of dairy cow feeding behaviour by traditional methods in complex breeding environments, and at the same time provide an important reference for the realization of intelligent animal husbandry and precision breeding.

The objective of this study was to investigate the current status and trends in antidepressant use and expenditure in China from 2013 to 2018. The study had a retrospective design based on prescribing data on antidepressant drugs, which was sourced from the Hospital Prescription Analysis Cooperative Project. The trends in hospital visits and corresponding expenditure on antidepressant drugs were examined. Subgroup analyses were carried out by sex, age, and drug class. A total of 1,795,230 outpatient prescriptions were collected from 79 hospitals in six major cities in China. Hospital visits with antidepressant prescriptions rose significantly from 244,626 in 2013 to 348,718 in 2018, reflecting a 42.6% increase (P < 0.05). The antidepressant expenditure also rose, increasing from 48.0 million Chinese yuan in 2013 to 64.8 million Chinese yuan in 2018. There were approximately 1.6 times more antidepressant prescriptions written for women than for men. The most frequent age category for antidepressant prescriptions was 45–64 years. The most commonly prescribed antidepressants were selective serotonin reuptake inhibitors (N06AB) and other antidepressants (N06AX), whereas tricyclic antidepressants (N06AA) accounted for only a small part of the total antidepressant prescriptions. Flupentixol/melitracen and escitalopram were the most frequently prescribed antidepressants. Antidepressant prescribing rates continue to increase in China, although the prescribing patterns have changed over the past few years. The wide use of expensive antidepressants and those with weak clinical evidence raises concerns regarding the rational use of antidepressants. This study provides a basis for future stewardship by the government and medical institutions.

OBJECTIVE:To evaluate the prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017. METHODS:A descriptive analysis using pharmacy prescription data was conducted. Outpatient prescription data was extracted from the Hospital Prescription Analysis Cooperative Project. Prescribing patterns, trends of visits, and corresponding expenditures for glaucoma medications were analyzed. RESULTS:A total of 84297 ambulatory prescriptions were included in the current study. Visits by glaucoma patients increased from 13808 in 2013 to 20060 in 2017. Over the same period, the yearly expenditure for glaucoma drugs increased from 2.33 million to 3.95 million Chinese Yuan (CNY). Among all the six classes of glaucoma drugs (prostaglandin analogues, carbonic anhydrase inhibitors, α-receptor agonists, β-receptor antagonists, cholinergic agonists and fixed combinations), β-receptor antagonists were the most commonly prescribed in 2013, accounting for 34.3% of patients, but gradually decreased to 27.1% in 2017. Prostaglandin analogues became the most frequently prescribed drugs in 2017, accounting for 30.2% of the visits. Prostaglandin analogues are the most expensive and yielded a total expenditure of 2.34 million CNY in 2017, followed by carbonic anhydrase inhibitors, α-receptor agonists, β-receptor antagonists, fixed combinations, and cholinergic agonists. Combination therapy became increasingly prescribed in 2017. CONCLUSION:Glaucoma prescribing practices exhibited substantial changes over the study period. The number of glaucoma prescriptions continuously increased from 2013 to 2017, leading to increased prescription costs. These findings implied a similar trend observed in previous studies, as well as recommendations in the appropriate guidelines.

[This corrects the article DOI: 10.1371/journal.pone.0227595.].

Topical anti-infectives are important in the management of ocular infections, but little is known about their current status and trends in their use in China. Thus, we carried out a prescription-based, cross-sectional study using the database of Hospital Prescription Analysis Projection of China, and aimed to analyze the trend in the use of ocular topical anti-infectives for outpatients of the ophthalmology department from 2013 to 2019. A total of 2,341,719 prescriptions from 61 hospitals located in six major areas written by ophthalmologists for outpatients were identified, and 1,002,254 of the prescriptions contained at least one anti-infective. The yearly anti-infective prescriptions increased continuously from 126,828 prescriptions in 2013 to 163,434 prescriptions in 2019. The cost also increased from 4,503,711 Chinese Yuan (CNY) in 2013 to CNY 5,860,945 in 2019. However, the use rate of anti-infectives decreased slightly from 46.5% in 2013 to 41.1% in 2019. Patients aged between 19 and 45 years old had the highest anti-infective use rate. Levofloxacin was the most frequently used anti-infective and kept on increasing among all age groups, occupying 67.1% of the total cost at the end of the study. Tobramycin was more frequently used in pediatric patients than in adults, but the use still decreased. Ganciclovir was the preferred anti-viral drug over acyclovir. In conclusion, the prescriptions and cost of ocular topical anti-infectives for outpatients both increased progressively. The increasingly widespread use of levofloxacin raised concerns regarding safety in pediatrics and resistance development. The observed trends can lead to the more efficient management of ocular anti-topical anti-infectives in China.

According to the International Energy Agency (IEA)’s forecast, China will fully electrify its railway system by 2050. However, the development of electrified railways is limited in the weak areas of China’s power grid. To surpass these limitations, we turn our attention to new railway energy sources, among which the most suitable is photovoltaic power generation. To evaluate the feasibility of integrating railway systems and photovoltaic power generation in China, this paper analyzes the geographical conditions and railway layout of China, gives a potential method for evaluating railway asset energy transformation measures and asset energy transformations that are suitable for China’s national conditions, and proposes an application of railway system energy transformation on this basis. Then, this method is used to evaluate the potential of a substation section of the Lanxin high-speed railway in China for reference. The results show that the green energy potential and scheduling potential of China’s railway assets are great and can effectively alleviate the energy anxiety of China’s railway system.

BACKGROUND:Meropenem exhibits time-dependent antimicrobial activity and prolonged infusion (PI) (extended infusion or continuous infusion, EI or CI) of meropenem can better achieve pharmacodynamics target when comparing with intermittent bolus (IB). However, the clinical outcomes between two groups remain inconclusive. OBJECTIVE:To evaluate current published literatures by meta-analysis to ascertain whether PI of meropenem can improve clinical outcomes. METHODS:Medline, Cochrane database and EMBASE were searched. Randomized control trails (RCT) and observational studies which compared the clinical outcomes of PI and IB groups were included and evaluated for quality. The data of studies were extracted and meta-analysis was performed using Revman 5.3 software. RESULTS:Six RCTs and 4 observation studies with relatively high quality were included in this analysis. Compared to IB group, PI group had a higher clinical success rate (odd ratio 2.10, 95% confidence interval 1.31-3.38) and a lower mortality (risk ratio 0.66, 95% confidence interval 0.50-0.88). The sensitivity analysis showed the results were stable. CONCLUSION:PI of meropenem was associated with a higher clinical improvement rate and a lower mortality. It is recommended for patients with severe infection or infected by less sensitive microbial.