Adequacy of the Dosing and Infusion Time of Ceftazidime/Avibactam for the Treatment of Gram-Negative Bacterial Infections: A PK/PD Simulation Study.

Introduction: Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets. Methods: This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR. Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%fT ≥ MIC and 100%fT ≥ CT=1.0 mg/L. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ CT=4.0 mg/L targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions. Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.

From graphite of used lithium-ion batteries to holey graphite coated by carbon with enhanced lithium storage capability.

The efficient recycling of waste graphite anode from used lithium-ion batteries (LIBs) has attracted considerable concerns mainly owing to the environment protection and reutilization of resources. Herein, we reported a rational and facile strategy for the synthesis of holey graphite coated by carbon (hG0.01@C0.10) through the separation, purification and creation of holey structures of waste graphite by using NaOH and carbon-coating by using phenolic resin. The holey structures facilitate the hG0.01@C0.10 with the quick penetration of electrolytes and rapid diffusion of Li+. The carbon coating is more favorable for hG0.01@C0.10 with improved electronic conductivity and less alleviated volume during the cycles. Benefiting from the synergistic effect of holey structures and carbon coating, the hG0.01@C0.10 as anode for LIBs displays a high reversible capacity of 377.6 mAh g-1 at 0.5 C and superior rate capabilities (e.g., 348.0 and 274.7 mAh g-1 at 1 and 2 C, respectively) and maintains a high reversible capacity of 278.7 mAh g-1 at 1 C after 300 cycles with an initial capacity retention of 80.0 %.

Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma.

Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.

Detection of α-Synuclein in Oral Mucosa by Seed Amplification Assay in Synucleinopathies and Isolated REM Sleep Behavior Disorder.

OBJECTIVE: Evidence of abnormal α-synuclein (α-Syn) deposition in the brain is required for definitive diagnosis of synucleinopathies, which remains challenging. The seed amplification assay (SAA) is an innovative technique that can detect the seeding activity of misfolded α-Syn, enabling the amplification and detection of minute quantities of pathogenic α-Syn aggregates. This study aimed to evaluate oral mucosa α-Syn SAA as possible diagnostic and prodromal biomarkers for synucleinopathies. METHODS: A total of 107 Parkinson's disease (PD) patients, 99 multiple system atrophy (MSA) patients, 33 patients with isolated rapid eye movement sleep behavior disorder (iRBD) and 103 healthy controls (HC) were included. The SAA was applied to detect the seeding activity of α-Syn from oral mucosa. A combination of morphological, biochemical, and biophysical methods was also used to analyze the fibrils generated from the oral mucosa α-Syn SAA. RESULTS: Structured illumination microscopy images revealed the increased α-Syn species in oral mucosa of PD, MSA, and iRBD patients than in HCs. Oral mucosa α-Syn SAA distinguished patients with PD from HC with 67.3% sensitivity and 90.3% specificity. Oral mucosa was α-Syn SAA positive in 53.5% MSA patients and 63.6% iRBD patients. Furthermore, the α-Syn fibrils generated from MSA demonstrated greater resistance to proteinase K digestion and exhibited stronger cytotoxicity compared to those from PD patients. CONCLUSION: Oral mucosa α-Syn seeding activity may serve as novel non-invasive diagnostic and prodromal biomarkers for synucleinopathies. The α-Syn aggregates amplified from the oral mucosa of PD and MSA exhibited distinct biochemical and biophysical properties. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Molecular beacon-based detection of circulating microRNA-containing extracellular vesicle as an α-synucleinopathy biomarker.

Early and precise diagnosis of α-synucleinopathies is challenging but critical. In this study, we developed a molecular beacon-based assay to evaluate microRNA-containing extracellular vesicles (EVs) in plasma. We recruited 1203 participants including healthy controls (HCs) and patients with isolated REM sleep behavior disorder (iRBD), α-synucleinopathies, or non-α-synucleinopathies from eight centers across China. Plasma miR-44438-containing EV levels were significantly increased in α-synucleinopathies, including those in the prodromal stage (e.g., iRBD), compared to both non-α-synucleinopathy patients and HCs. However, there are no significant differences between Parkinson's disease (PD) and multiple system atrophy. The miR-44438-containing EV levels negatively correlated with age and the Hoehn and Yahr stage of PD patients, suggesting a potential association with disease progression. Furthermore, a longitudinal analysis over 16.3 months demonstrated a significant decline in miR-44438-containing EV levels in patients with PD. These results highlight the potential of plasma miR-44438-containing EV as a biomarker for early detection and progress monitoring of α-synucleinopathies.

An enhancement algorithm for head characteristics of caged chickens detection based on cyclic consistent migration neural network.

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.

Trends and prescribing patterns of antimigraine medicines in nine major cities in China from 2018 to 2022: a retrospective prescription analysis.

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 <  0.001). The most frequently prescribed preventive medication classes were calcium channel blockers (CCBs; 51.59%), followed by antidepressants (20.59%) and anticonvulsants (15.82%), which accounted for 21.90%, 34.18%, and 24.15%, respectively, of the total preventive expenditures. Flunarizine (51.41%) was the most commonly prescribed preventive drug. Flupentixol/melitracen (7.53%) was the most commonly prescribed antidepressant. The most commonly prescribed anticonvulsant was topiramate (9.33%), which increased from 6.26% to 12.75% (both P <  0.001). A total of 3.88% of the patients received combined therapy for acute migraine treatment, and 18.63% received combined therapy for prevention. The prescriptions for 69.21% of opioids, 38.53% of caffeine-containing agents, 26.61% of NSAIDs, 13.97% of acetaminophen, and 6.03% of triptans were considered written medicine overuse. CONCLUSIONS: Migraine treatment gradually converges toward evidence-based and guideline-recommended treatment. Attention should be given to opioid prescribing, weak evidence-based antidepressant use, and medication overuse in migraine treatment.

Prevalence of inappropriateness of elemene injection for hospitalized cancer patients: a multicenter retrospective study.

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.

Model-Informed Precision Dosing of Imipenem in an Obese Adolescent Patient with Augmented Renal Clearance and History of Schizophrenia.

Imipenem is a broad-spectrum antibiotic that has been used in treating severe infections and exhibits a time-dependent PK/PD profile. Its dose should be adjusted based on renal function. However, there is little experience with imipenem dosing in obese adolescent patients with augmented renal clearance (ARC) and history of schizophrenia. This case reported successful dosing of imipenem in an obese adolescent patient with ARC based on therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD). A 15-year-old male adolescent patient with history of schizophrenia was diagnosed with ventilator-associated pneumonia due to carbapenem-susceptible Klebsiella pneumoniae and received imipenem treatment (0.5 g every 8 hours with a 1-hour infusion). However, the exposure of imipenem was suboptimal due to ARC, and there is no available model for MIPD in this patient. Thus, we utilized prediction error to find a population pharmacokinetic model that fit this patient and ran Maximum a posteriori Bayesian estimation and Monte Carlo simulation based on screened models to predict changes in drug concentrations. The dose of imipenem was adjusted to 0.5 g every 6 hours with a 2-hour infusion, and subsequent TDM revealed that dosing adjustment was accurate and successful. Finally, the patient's status of infection improved. This study will be beneficial to imipenem dosing in similar cases in the future, thereby improving the safety and effectiveness of imipenem or other antibiotics.

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)-rich ADEVs in patients with AQP4-Abs-positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE130-149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor-related protein 1 (LRP1) could block the restorative effects of APOE130-149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE-/- mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.

Population pharmacokinetics and individualized dosing of tigecycline for critically ill patients: a prospective study with intensive sampling.

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.

GV-971 attenuates α-Synuclein aggregation and related pathology.

RATIONALE: Synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), share a distinct pathological feature, that is, a widespread accumulation of α-synuclein (α-syn) in the brain. There is a significant clinical unmet need for disease-modifying treatments for synucleinopathies. Recently, a seaweed-derived mixture of oligosaccharides sodium oligomannate, GV-971, was approved for Phase 2 clinical trials for PD. This study aimed to further evaluate the therapeutic effects of GV-971 on synucleinopathies using cellular and animal models and explore its associated molecular mechanisms. METHODS: α-Syn aggregation was assessed, in vitro and ex vivo, by ThT assay. A dopaminergic neuron cell line, Prnp-SNCAA53T mice, and brain slices from PD and DLB patients were used to determine the efficacy of GV-971 in ameliorating α-syn pathology. Measurements of motor functions, including pole, cylinder, and rotarod tests, were conducted on Prnp-SNCAA53T mice 4 weeks after intragastric administration of GV-971 (200 mg day-1 kg-1 ). RESULTS: GV-971 effectively prevented α-syn aggregation and even disassembled pre-aggregated α-syn fibrils, in vitro and ex vivo. In addition, GV-971 was able to rescue α-syn-induced neuronal damage and reduced release of extracellular vesicles (EVs), likely via modulating Alix expression. In the Prnp-SNCAA53T mouse model, when treated at the age of 5 months, GV-971 significantly decreased α-syn deposition in the cortex, midbrain, and cerebellum regions, along with ameliorating the motor dysfunctions. CONCLUSIONS: Our results indicate that GV-971, when administered at a relatively early stage of the disease process, significantly reduced α-syn accumulation and aggregation in Prnp-SNCAA53T mice. Furthermore, GV-971 corrected α-syn-induced inhibition of EVs release in neurons, contributing to neuronal protection. Future studies are needed to further assess GV-971 as a promising disease-modifying therapy for PD and other synucleinopathies.

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy.

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.

Erythrocytic alpha-synuclein as potential biomarker for the differentiation between essential tremor and Parkinson's disease.

Introduction: The 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. Methods: This 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. Results: We 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. Conclusion: Our findings suggest new insight into the changes of erythrocytic total and aggregated α-syn levels as potential biomarkers for ET patients.

α-Synuclein-carrying astrocytic extracellular vesicles in Parkinson pathogenesis and diagnosis.

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.

Conductive Polyaniline-Based Microwire Arrays for SO2 Gas Detection.

Polyaniline-based conductive polymers are promising electrochemical sensor materials due to their unique physical and chemical properties, such as good gas absorption, low dielectric loss, and chemical and thermal stabilities. The sensing performance is highly dependent on the structure and dimensions of the polyaniline-based conductive polymers. Although in situ oxidative polymerization combined with the self-assembly process has become one of the main processes for the preparation of flexible polyaniline-based gas sensors, how to prepare polyaniline materials into uniformly arranged microwire arrays is still an urgent problem. In this paper, an in-depth study was conducted on the preparation of polyaniline microwire arrays by combining a wettability interface dewetting process and a liquid-film-induced capillary bridges method. The factors influencing the preparation of polyaniline microwire arrays, including solution concentration, template width, evaporation temperature, and evaporation time, were investigated in detail. The wire formation rates were recorded from the results of SEM images. 100% microwires formation rate can be obtained by using a 1.0 mg mL-1 concentration of polyaniline solution and a 10 µm silicon template at an evaporation temperature of 80 °C for 18 h. The prepared microwire arrays can realize sulfur dioxide sensing at room temperature with a response speed of about 20 s and can detect sulfur dioxide gas as low as 1 ppm. Thus, the liquid-film-induced capillary bridge method shows a new possibility to prepare gas sensor devices for insoluble polymers.

Comparison of biospecimens for α-synuclein seed amplification assays in Parkinson's disease: A systematic review and network meta-analysis.

BACKGROUND AND PURPOSE: Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is limited consensus regarding the diagnostic and differential diagnostic performance of α-syn SAAs on biofluids and peripheral tissues. METHODS: A comprehensive research was performed in PubMed, Web of Science, Embase and Cochrane Library. Meta-analysis was performed using a random-effects model. A network meta-analysis based on an ANOVA model was conducted to compare the relative accuracy of α-syn SAAs with different specimens. RESULTS: The pooled sensitivity and specificity of α-syn SAAs in distinguishing PD from healthy controls or non-neurodegenerative neurological controls were 0.91 (95% confidence interval [CI] 0.89-0.92) and 0.95 (95% CI 0.94-0.96) for cerebrospinal fluid (CSF); 0.91 (95% CI 0.86-0.94) and 0.92 (95% CI 0.87-0.95) for skin; 0.80 (95% CI 0.66-0.89) and 0.87 (95% CI 0.69-0.96) for submandibular gland; 0.44 (95% CI 0.30-0.59) and 0.92 (95% CI 0.79-0.98) for gastrointestinal tract; 0.79 (95% CI 0.70-0.86) and 0.88 (95% CI 0.77-0.95) for saliva; and 0.51 (95% CI 0.39-0.62) and 0.91 (95% CI 0.84-0.96) for olfactory mucosa (OM). The pooled sensitivity and specificity were 0.91 (95% CI 0.89-0.93) and 0.50 (95% CI 0.44-0.55) for CSF, 0.92 (95% CI 0.83-0.97) and 0.22 (95% CI 0.06-0.48) for skin, and 0.55 (95% CI 0.42-0.68) and 0.50 (95% CI 0.35-0.65) for OM in distinguishing PD from multiple system atrophy. The pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.84 (95% CI 0.73-0.91) for CSF, 0.92 (95% CI 0.83-0.97) and 0.88 (95% CI 0.64-0.99) for skin and 0.63 (95% CI 0.52-0.73) and 0.86 (95% CI 0.64-0.97) for OM in distinguishing PD from progressive supranuclear palsy. The pooled sensitivity and specificity were 0.94 (95% CI 0.90-0.97) and 0.95 (95% CI 0.77-1.00) for CSF and 0.94 (95% CI 0.84-0.99) and 0.86 (95% CI 0.42-1.00) for skin in distinguishing PD from corticobasal degeneration. CONCLUSIONS: α-Synuclein SAAs of CSF, skin, saliva, submandibular gland, gastrointestinal tract and OM are promising diagnostic assays for PD, with CSF and skin α-syn SAAs demonstrating higher diagnostic performance.