•We develop a new method on solving the high-dimensional ODEs with variable coefficients, based on which we get the analytical solution of the stationary distribution of the voltage uctuation driven ...by a single nACh receptor.•We put forward a new concept on the energy consuming efficiency of the membrane system. The ratio of the depolarized potential to the dissipated power is used to characterize it.•By comparison of the energy consuming efficiency of two models with same kinetic structure but different parameter values, the ways of several factors that influence the efficiency are clarified.
The depolarization of the postsynaptic membrane potential in neuromuscular junction, which is conducted by the (stochastic) opening of nicotinic acetylcholine (nACh) receptors distributed in postsynaptic folds, is an inevitable stage in transmitting the electric signals from neural ends to muscle fibers. To perform this work, free energy must be dissipated. Being the first step in understanding the speech-accuracy-energy trade-off, we calculate the energy dissipation of a tiny membrane system that contains a single nACh receptor, i which firstly the stationary distribution of voltage is calculated based on our new method on solving the high-dimensional ODEs with variable coefficients. The ratio of the extent of depolarized-potential to the dissipated power is used to characterize the energy consuming efficiency of the system.
Left atrial appendage occlusion (LAAO) provides an alternative for poor candidates of long-term oral anticoagulant (OAC) therapy; however, anticoagulant therapy after surgical procedures has limited ...use due to associated uncertainties. We aimed to evaluate the effectiveness and safety of the short-term use of direct oral anticoagulant (DOAC) and warfarin after LAAO.
Electronic databases such as PubMed, Embase, Medline, and Cochrane Library databases were searched up to November 11, 2022. Our study compared DOAC therapy and warfarin in patients after LAAO. A meta-analysis was conducted with the Review Manager software (version 5.4).
The meta-analysis included 13 cohort studies with a total of 32,607 patients. Our findings indicated that the incidence of stroke/TIA/SE, peri-device leaks>5 mm, device-related thrombosis, and all-cause mortality were not significantly different between the two groups after LAAO (P > 0.05). The DOAC group had a significantly lower incidence of major bleeding (OR = 0.83, 95 % CI: 0.74-0.94, P = 0.003), any bleeding (OR = 0.34, 95 % CI: 0.23-0.51, P < 0.001), stroke/TIA/SE and major bleeding (OR = 0.57, 95 % CI: 0.34-0.95, P = 0.03), and any major adverse event (OR = 0.89, 95 % CI:0.82-0.97, P = 0.010) than the warfarin group. The subgroup analysis revealed that the rate of stroke/TIA/SE was similar in the two groups in terms of the different regions, follow-up time, study type, anticoagulant strategy, and bleeding risk. The incidence of major bleeding in the DOAC group was significantly lower than that in the warfarin group in North America, as well as at follow-up period ≤6 months, retrospective cohort, HAS-BLED average score ≥ 3. In addition, the risk of major bleeding was higher with the combination of OAC and single antiplatelet therapy (SAPT) than with OAC alone. Finally, in the North American region, retrospective cohort, and HAS-BLED average score ≥ 3, the incidence of any serious adverse event in the DOAC group was still significantly lower than that in the warfarin group.
Compared to warfarin, DOAC reduced the risk of major bleeding and any serious adverse event in patients after LAAO. This advantage was particularly notable in North America and high-risk populations for bleeding. In addition, the incidence of device-related thrombosis, peri-device leaks, stroke/TIA/SE and all-cause mortality were similar in both groups. The risk of major bleeding was lower in patients taking OAC alone compared with those taking OAC plus SAPT, without increasing the risk of thrombosis.
Microseismic monitoring technology has become an important technique to assess stability of rock mass in metal mines. Due to the special characteristics of underground metal mines in China, including ...the high tectonic stress, irregular shape and existence of ore body, and complex mining methods, the application of microseismic technology is more diverse in China compared to other countries, and is more challenging than in other underground structures such as tunnels, hydropower stations and coal mines. Apart from assessing rock mass stability and ground pressure hazards induced by mining process, blasting, water inrush and large scale goaf, microseismic technology is also used to monitor illegal mining, and track personnel location during rescue work. Moreover, microseismic data have been used to optimize mining parameters in some metal mines. The technology is increasingly used to investigate cracking mechanism in the design of rock mass supports. In this paper, the application, research development and related achievements of microseismic technology in underground metal mines in China are summarized. By considering underground mines from the perspective of informatization, automation and intelligentization, future studies should focus on intelligent microseismic data processing method, e.g., signal identification of microseismic and precise location algorithm, and on the research and development of microseismic equipment. In addition, integrated monitoring and collaborative analysis for rock mass response caused by mining disturbance will have good prospects for future development.
Electrospun (e-spun) nanofibers for wound dressing have attracted wide attention due to its large specific surface area, large porosity and breathability. Compared with solution electrospinning ...(e-spinning), melt e-spinning is more bio-friendly without toxic solvent participation, which provides the possibility of in situ e-spinning on wounds directly. However, previously reported melt e-spinning devices were usually bulky and cumbersome due to their necessary heating unit, and different components were separated to avoid electrostatic interference.
In this article, we report on a self-powered hand-held melt e-spinning gun which can work without any external power supply (outdoors). The problem of electrostatic interference for this integrated device was solved by using a special high heat transfer insulation unit. The apparatus is easy and safe to operate by a single hand due to its small volume (24 × 6 × 13 cm
) and light weight (about 450 g). Some biodegradable polymers, for example, polycaprolactone (PCL) fibers were successful e-spun onto wounds directly by using this dressing gun.
PCL fibrous membrane has good biocompatibility and can be in situ electrospun to wound surface as a wound dressing by the portable melt e-spinning gun. Besides wound dressing, this hand-held melt e-spinning gun may be used in 3D printing and experimental teaching demonstration aids.
Background and Aims: Type 2 diabetes (T2D) is a global and complex public health challenge, and dietary management is acknowledged as critical in its prevention. Recent studies have highlighted the ...involvement of micronutrients in T2D pathophysiology; our study aims to assess the association between B vitamin intake and T2D risks and the mediating role of inflammation. Methods: In a prospective cohort design, data on B vitamins intake, including thiamine (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), folate (B9), and cobalamin (B12), was obtained using a validated food frequency questionnaire (FFQ), and blood inflammatory biomarkers were analyzed according to standard protocol in the local hospitals at baseline from 44,960 adults in the Shanghai Suburban Adult Cohort and Biobank (SSACB). Incident T2D cases were identified according to a physician’s diagnosis or medication records from the electronic medical information system. We employed logistic and weighted quantile sum regression models to explore the associations of single and combined levels of B vitamins with T2D and mediation analyses to investigate the effects of inflammation. Results: Negative correlations between B vitamins and T2D were observed in the single-exposure models, except for B3. The analyses of joint exposure (B1, B2, B6, B9, and B12) also showed an inverse association (OR 0.80, 95% CI 0.71 to 0.88), with vitamin B6 accounting for 45.58% of the effects. Further mediation analysis indicated a mediating inflammatory impact, accounting for 6.72% of the relationship. Conclusions: Dietary intake of B vitamins (B1, B2, B6, B9, B12) was associated with a reduced T2D risk partially mediated by inflammation in Shanghai residents.
To tackle the network congestion problem caused by ground gateway stations arranged within a limited area in low earth orbit (LEO) satellite networks, a routing algorithm based on segment routing for ...traffic return is proposed. Light and heavy load zones are dynamically divided according to the relative position relationship between gateways and the reverse slot. The pre-balancing shortest path algorithm is used in the light load zone, and the minimum weight path defined by congestion index is the routing rule in the heavy load zone. Then, the consistent forwarding is performed referring to segment routing in all zones. Simulation conditions are different sizes of heavy load zone, different traffic density distributions, and different traffic demands. Simulation results confirm that the load-balancing performance is improved significantly with the extension of the heavy load zone size in terms of the average rejection ratio, the average relative throughput, the maximum link utilization, and the average delay. The proposed algorithm is an alternative solution and guidance for routing strategy in LEO satellite networks.
Treating persistent, recurrent, or metastatic cervical cancer remains challenging. Although pembrolizumab, combined with chemotherapy and bevacizumab, offers a promising first-line option, its ...cost-effectiveness within the Chinese healthcare system has not been established.
A partitioned survival model was constructed using patient data from the KEYNOTE-826 trial. Efficacy, safety, and economic data from both trial and real-world practices were utilized to determine the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of the treatment strategies. Comprehensive insights were gained through the sensitivity and subgroup analyses.
Over five years, the combination of pembrolizumab, chemotherapy, and bevacizumab offered an additional 1.18 QALYs compared to that provided by standard treatments. This regimen increased the costs by US$ 134,502.57, resulting in an ICER of US$ 114,275.67 per QALY, relative to traditional treatment costs. The ICER for the pembrolizumab regimen was further calibrated to be US$ 52,765.69 per QALY. Both ICER values surpassed China's established willingness-to-pay threshold. Importantly, subgroup analysis revealed enhanced cost-effectiveness in patients presenting with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥10.
Introducing pembrolizumab alongside chemotherapy and bevacizumab may not be a cost-effective primary strategy for advanced cervical cancer against current standards. However, for patients with a PD-L1 CPS ≥10, the therapeutic and economic outcomes could be improved by adjusting the pembrolizumab price.
The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a history of intracranial hemorrhage ...(ICH) remain controversial. We performed a systematic review and meta-analysis to compare the safety and efficacy of starting oral anticoagulation (OAC) and non-oral anticoagulation in these patients.
PubMed, Cochrane Library, and Embase were searched from inception to 01 May 2022 for randomized controlled trials and cohort studies, reporting effectiveness and safety outcomes for anticoagulation therapy in atrial fibrillation patients with intracranial hemorrhage. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration tool were used to evaluate bias risks for all randomized controlled trials (RCTs) and cohort studies. An effects model was applied to calculate adjusted hazard ratios (aHRs) for randomized controlled trials and cohort studies.
We analyzed data from two randomized controlled trials (304 patients) and seven Cohort studies (17,477 patients). Compared to non-oral anticoagulation, starting oral anticoagulation therapy reduced the risk of Ischemic Stroke/Systemic Embolism (SE) (aHR: 0.64, 95% CI: 0.55-0.57) and all-cause death (aHR: 0.53, 95% CI: 0.35-0.80) in atrial fibrillation patients and a prior history intracranial hemorrhage. Starting oral anticoagulation therapy did not increase the risk of recurrent intracranial hemorrhage (aHR: 1.07, 95% CI: 0.66-1.74), but increased the risk of major bleeding (aHR: 1.38, 95% CI: 1.00-1.91) than no oral anticoagulation therapy. The DOACs had a lower risk of Ischemic Stroke/SE (aHR: 0.84, 95% CI: 0.70-1.00), recurrent intracranial hemorrhage (aHR: 0.63, 95% CI: 0.49-0.82), and all-cause death (aHR: 0.65, 95% CI: 0.48-0.88) compared to warfarin. According to subgroup analyses, starting oral anticoagulation therapy have a higher risk of recurrent intracranial hemorrhage than non-oral anticoagulation therapy (aHR: 1.57, 95% CI: 1.36-1.81) for Asians.
After intracranial hemorrhage in atrial fibrillation patients, restarting or initiating oral anticoagulation therapy decreased the risk of Ischemic Stroke/SE and all-cause death but did not increase the risk for recurrent intracranial hemorrhage. Direct oral anticoagulations have better efficacy and safety than warfarin if oral anticoagulation therapy is started. However, starting oral anticoagulation increases the risk for recurrent intracranial hemorrhage in the Asian region.
Objectives
This study aimed to establish a neural‐related gene risk score (NRGRS) for the prediction of head and neck squamous cell carcinoma prognosis and explore its predictive value on the benefit ...of immune checkpoint inhibitor therapy.
Methods
Based on the transcriptome data of HNSCC patients (n = 546) from The Cancer Genome Atlas database, 37 neural‐related hub genes were identified by weighted gene co‐expression network analysis. Four genes (ITGA5, PYGM, GNG7 and ATP2A3) were identified to construct NRGRS using Lasso‐Cox regression method based on the derivation cohort and validated in the Gene Expression Omnibus cohort (n = 109). The survival analysis was performed to validate the prognostic value of NRGRS and immune characteristics in NRGRS‐defined subgroups were analyzed.
Results
NRGRS‐high patients had a worse overall survival than NRGRS‐low patients. Tumors with high NRGRS were more likely to have high infiltration of naive CD4+ T cells, M0, M2 macrophages and resting mast cells, which illustrated suppressive immunity and less benefit from immunotherapy therapy.
Conclusion
NRGRS strongly correlates with survival and is a promising biomarker to predict immunotherapy benefits for head and neck cancer patients. This study provides evidence for the potential correlation between neural‐related transcriptome alteration and immune activity.
•We get the analytical solution of the power spectrum of the voltage fluctuation driven by a single nACh receptor.•For the first time, it is revealed that the voltage fluctuations show the 1/ω4-type ...noise, which is different from the commonly known 1/ω2 noise.•The results may be used to infer the kinetic structures of the receptor; and the analytical method can be applied to other kinds of ligand-gated channels.
Being the primary mean of translating the chemical signal into the electric signal in neuromuscular junction, the nACh receptor is the first kind of ligand-gated channel that its kinetic structure has been known clearly. The next problem is to know quantitatively how it works in a living system. In this paper, we construct a piece-wise deterministic process to mimic the membrane voltage fluctuation driven by a single nACh receptor. The power spectrum of the voltage fluctuation is solved analytically, which reveals the 1/ω4-type noise.
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