Evolutionary Subnetworks in Complex Systems

Links in a practical network may have different functions, which makes the original network a combination of some functional subnetworks. Here, by a model of coupled oscillators, we investigate how such functional subnetworks are evolved and developed according to the network structure and dynamics. In particular, we study the case of evolutionary clustered networks in which the function of each link (either attractive or repulsive coupling) is updated by the local dynamics. It is found that, during the process of system evolution, the network is gradually stabilized into a particular form in which the attractive (repulsive) subnetwork consists only the intralinks (interlinks). Based on the properties of subnetwork evolution, we also propose a new algorithm for network partition which is distinguished by the convenient operation and fast computing speed.Comment: 4 pages, 4 figure

Bioequivalence and Population Pharmacokinetic Modeling of Two Forms of Antibiotic, Cefuroxime Lysine and Cefuroxime Sodium, after Intravenous Infusion in Beagle Dogs

To investigate the bioequivalence and the population pharmacokinetics of cefuroxime lysine and cefuroxime sodium in healthy beagle dogs. A randomized 2-period crossover design in 18 healthy beagle dogs after receiving 20, 40, and 80 mg/kg of cefuroxime lysine or cefuroxime sodium was conducted. A 3-compartment open model was used as the basic model for the population pharmacokinetic study. Both of the antibiotics exhibited dose-proportional pharmacokinetics over the dose range of 20–80 mg/kg. The mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium was 1.05 (range, 0.71 to 1.42), with a significant difference between males and females. The estimates of population pharmacokinetic of CL, V1, Q2, V2, Q3, V3 were 3.74 mL/h, 1.70 mL, 29.5 mL/min, 3.58 mL, 0.31 mL/min, and 158 mL for cefuroxime lysine and 4.10 mL/h, 1.00 mL, 38.5 mL/min, 4.19 mL, 0.06 mL/min, and 13.6 mL for cefuroxime sodium, respectively. The inter-individual variability was determined to be less than 29.1%. A linear pharmacokinetic was revealed for cefuroxime lysine and cefuroxime sodium in dogs after intravenous infusion, and the bioequivalence of these forms of the antibiotic was observed with the significant gender-related differences in mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium

Design and assessment of a reconfigurable behavioral assistive robot: a pilot study

IntroductionFor patients with functional motor disorders of the lower limbs due to brain damage or accidental injury, restoring the ability to stand and walk plays an important role in clinical rehabilitation. Lower limb exoskeleton robots generally require patients to convert themselves to a standing position for use, while being a wearable device with limited movement distance.MethodsThis paper proposes a reconfigurable behavioral assistive robot that integrates the functions of an exoskeleton robot and an assistive standing wheelchair through a novel mechanism. The new mechanism is based on a four-bar linkage, and through simple and stable conformal transformations, the robot can switch between exoskeleton state, sit-to-stand support state, and wheelchair state. This enables the robot to achieve the functions of assisted walking, assisted standing up, supported standing and wheelchair mobility, respectively, thereby meeting the daily activity needs of sit-to-stand transitions and gait training. The configuration transformation module controls seamless switching between different configurations through an industrial computer. Experimental protocols have been developed for wearable testing of robotic prototypes not only for healthy subjects but also for simulated hemiplegic patients.ResultsThe experimental results indicate that the gait tracking effect during robot-assisted walking is satisfactory, and there are no sudden speed changes during the assisted standing up process, providing smooth support to the wearer. Meanwhile, the activation of the main force-generating muscles of the legs and the plantar pressure decreases significantly in healthy subjects and simulated hemiplegic patients wearing the robot for assisted walking and assisted standing-up compared to the situation when the robot is not worn.DiscussionThese experimental findings demonstrate that the reconfigurable behavioral assistive robot prototype of this study is effective, reducing the muscular burden on the wearer during walking and standing up, and provide effective support for the subject's body. The experimental results objectively and comprehensively showcase the effectiveness and potential of the reconfigurable behavioral assistive robot in the realms of behavioral assistance and rehabilitation training

Decaying Hidden Dark Matter in Warped Compactification

The recent PAMELA and ATIC/Fermi/HESS experiments have observed an excess of electrons and positrons, but not anti-protons, in the high energy cosmic rays. To explain this result, we construct a decaying hidden dark matter model in string theory compactification that incorporates the following two ingredients, the hidden dark matter scenario in warped compactification and the phenomenological proposal of hidden light particles that decay to the Standard Model. In this model, on higher dimensional warped branes, various warped Kaluza-Klein particles and the zero-mode of gauge field play roles of the hidden dark matter or mediators to the Standard Model.Comment: 15 pages; v4, several clarifications added, update on Fermi/HESS result

Deaths and adverse events from adjuvant therapy with immune checkpoint inhibitors in solid malignant tumors: A systematic review and network meta‐analysis

Abstract Background By prolonging overall survival and reducing disease recurrence rates, immune checkpoint inhibitors (ICIs) are an emerging adjuvant therapy option for patients with resectable malignant tumors. However, the safety profile (deaths and adverse events [AEs]) of adjuvant ICIs has not been fully described. Methods We searched the literature for phase III randomized clinical trials that compared PD‐1, PD‐L1, and CTLA‐4 inhibitors in solid malignant tumors. Incidences of death, discontinuation, AEs of any cause, treatment‐related adverse events (TRAEs), and immune‐related adverse events (IRAEs) were extracted for the network meta‐analysis. Network meta‐analyses with low incidence and poor convergence are reported as incidences with 95% confidence intervals (95% CIs). Results Ten randomized clinical trials that included 9243 patients who received ICI adjuvant therapy were eligible. In total, 21 deaths due to TRAEs were recorded, with an overall incidence of 0.40% (95% CI: 0.26–0.61). The treatment‐related mortality rates for ipilimumab (0.76%, 95% CI: 0.31–1.55) and atezolizumab (0.56%, 95% CI: 0.18–1.31) were higher than for pembrolizumab (0.24%, 95% CI: 0.10–0.56) and nivolumab (0.30%, 95% CI: 0.08–0.77). The most frequent causes of death were associated with the gastrointestinal (0.10%, 95% CI: 0.04–0.24) and pulmonary (0.08%, 95% CI: 0.03–0.21) systems. Compared with the control arm, we found that nivolumab (odds ratio [OR]: 2.73, 95% CI: 0.49–15.85) and atezolizumab (OR: 12.43, 95% CI: 2.42–78.48) caused the fewest grade ≥3 TRAEs and IRAEs. Commonly reported IRAEs of special interest were analyzed, and two agents were found to have IRAEs with incidences >10%, i.e., hepatitis for atezolizumab (14.80%, 95% CI: 12.53–17.32) and hypophysitis for ipilimumab (13.53%, 95% CI: 11.38–15.90). Conclusions Ipilimumab and atezolizumab were correlated with higher treatment‐related death rates than pembrolizumab and nivolumab, in which the gastrointestinal and pulmonary systems were mostly involved. Regarding severe TRAEs and IRAEs, nivolumab and atezolizumab are likely to be the safest agent, respectively. This study will guide clinical practice for ICI adjuvant therapies

Neutrophil extracellular traps in relationship to efficacy of systemic therapy for metastatic renal cell carcinoma

Abstract Background The efficacy of systemic therapy regimens, such as immune checkpoint inhibitors and tyrosine kinase inhibitors (IO‐TKI) and targeted therapy, for metastatic clear cell renal cell carcinoma (ccRCC) remains unpredictable due to the lack of effective biomarkers. Neutrophil extracellular trap (NET) plays an important role in promoting ccRCC. This study explores the NET predictive value of the efficacy in metastatic ccRCC. Methods In this retrospective study, patients with metastatic ccRCC who received targeted drugs and IO‐TKI were included. Immunofluorescence staining was utilized to quantify the levels of tissue NETs through cell counts of H3Cit(+) and MPO(+) cells. Results A total of 183 patients with metastatic ccRCC were enrolled, including 150 patients who received TKIs and 33 patients who received IO‐TKI. The levels of NETs in tumor tissue were significantly higher than in para‐tumor tissue (p < 0.001). In terms of predicting drug efficacy, a correlation between NET levels and progression‐free survival (PFS) was observed in the TKI with metachronous metastasis group (HR 1.73 [95% CI 1.02–2.91], log‐rank p = 0.037), while no correlation was observed in the TKI with synchronous metastasis group and IO‐TKI group. Regarding overall survival (OS), activated NET levels were associated with poor OS in both TKI (HR 1.60 [95% CI 1.05–2.43], log‐rank p  = 0.017) and IO‐TKI group (HR 4.35 [95% CI 1.06–17.82], log‐rank p =0.047). IMDC score (HR 1.462 [95% CI 1.030–2.075], p = 0.033) and tumor tissue NET levels (HR 1.733 [95% CI 1.165–2.579], p = 0.007) were independent prognostic risk factors for OS in patients with metastatic ccRCC.NET level was associated with poor OS in both TKI (HR 1.60 [95% CI 1.05–2.43], log‐rank p  = 0.017). Conclusions The active NET levels in tumor tissue can predict drug efficacy in patients with metastatic ccRCC who received systemic therapy. Elevated levels of NETs in tumor tissue were also associated with poor efficacy in OS