Laplacian eigenvalue distribution, diameter and domination number of trees

For a graph $G$ with domination number $\gamma$, Hedetniemi, Jacobs and Trevisan [European Journal of Combinatorics 53 (2016) 66-71] proved that $m_{G}[0,1)\leq \gamma$, where $m_{G}[0,1)$ means the number of Laplacian eigenvalues of $G$ in the interval $[0,1)$. Let $T$ be a tree with diameter $d$. In this paper, we show that $m_{T}[0,1)\geq (d+1)/3$. However, such a lower bound is false for general graphs. All trees achieving the lower bound are completely characterized. Moreover, for a tree $T$, we establish a relation between the Laplacian eigenvalues, the diameter and the domination number by showing that the domination number of $T$ is equal to $(d+1)/3$ if and only if it has exactly $(d+1)/3$ Laplacian eigenvalues less than one. As an application, it also provides a new type of trees, which show the sharpness of an inequality due to Hedetniemi, Jacobs and Trevisan

Prediction of pediatric dose of tirzepatide from the reference adult dose using physiologically based pharmacokinetic modelling

Tirzepatide is an emerging hypoglycemic agent that has been increasing used in adults, yet its pharmacokinetic (PK) behavior and dosing regimen in pediatric population remain unclear. This study aimed to employ the physiologically based pharmacokinetic (PBPK) model to predict changes of tirzepatide exposure in pediatric population and to provide recommendations for its dose adjustments. A PBPK model of tirzepatide in adults was developed and verified by comparing the simulated plasma exposure with the observed data using PK-Sim&MoBi software. This model was then extrapolated to three specific age subgroups, i.e., children (10–12 years), early adolescents (12–15 years), and adolescents (15–18 years). Each subgroup included healthy and obese population, respectively. All known age-related physiological changes were incorporated into the pediatric model. To identify an appropriate dosing regimen that yielded PK parameters which were comparable to those in adults, the PK parameters for each aforementioned subgroup were predicted at pediatric doses corresponding to 87.5%, 75%, 62.5%, and 50% of the adult reference dose. According to the results of simulation, dose adjustments of tirzepatide are necessary for the individuals aged 10–12 years, as well as those aged 12–15 years with healthy body weights. In conclusion, the adult PBPK model of tirzepatide was successfully developed and validated for the first time, and the extrapolated pediatric model could be used to predict pediatric dosing regimen of tirzepatide, which will provide invaluable references for the design of future clinical trials and its rational use in the pediatric population

Weighted Graph Clustering for Community Detection of Large Social Networks

AbstractThis study mainly focuses on the methodology of weighted graph clustering with the purpose of community detection for large scale networks such as the users’ relationship on Internet social networks. Most of the networks in the real world are weighted networks, so we proposed a graph clustering algorithm based on the concept of density and attractiveness for weighted networks, including node weight and edge weight. With deep analysis on the Sina micro-blog user network and Renren social network, we defined the user's core degree as node weight and users’ attractiveness as edge weight, experiments of community detection were done with the algorithm, the results verify the effectiveness and reliability of the algorithm. The algorithm is designed to make some breakthrough on the time complexity of Internet community detection algorithm, because the research is for large social networks. And the another advantage is that the method does not require to specify the number of clusters

Efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus: a Bayesian network meta-analysis

BackgroundAs a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a Bayesian network meta-analysis was conducted to evaluate the efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus (T2DM).MethodsWe systematically searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing teneligliptin with placebo or active comparators in T2DM patients for at least 12 weeks were included in the study. Data analysis was performed using R 4.2.3 and Stata 17.0 software. Each outcome was presented as a mean difference (MD) or an odds ratio (OR) along with 95% confidence interval (CI) and the surface under the cumulative ranking curve value (SUCRA).ResultsA total of 18 RCTs with 3,290 participants with T2DM were included in this study. Generally, compared to placebo, sitagliptin, vildagliptin, metformin, and bromocriptine, 20 mg of teneligliptin showed better efficacy in reducing HbA1c (MD [95% CI], −0.78 [−0.86 to −0.70], −0.08 [−0.36 to 0.19], −0.04 [−0.72 to 0.60], −0.12 [−0.65 to 0.42], and −0.50 [−0.74 to −0.26], respectively) and fasting plasma glucose (FPG) (MD [95% CI], −18.02 [−20.64 to −15.13], 1.17 [−9.39 to 11.70], −8.06 [−30.95 to 14.35], −2.75 [−18.89 to 13.01], and −34.23 [−45.93 to −22.96], respectively), and 40 mg of teneligliptin also showed better efficacy in reducing HbA1c (MD [95% CI], −0.84 [−1.03 to −0.65], −0.15 [−0.49 to 0.19], −0.10 [−0.81 to 0.57], −0.18 [−0.76 to 0.39], and −0.56 [−0.88 to −0.26], respectively) and FPG (MD [95% CI], −20.40 [−26.07 to −14.57], −1.20 [−13.21 to 10.38], −10.43 [−34.16 to 12.65], −5.13 [−22.21 to 11.66], and −36.61 [−49.33 to −24.01], respectively). Compared to placebo, 20 mg of teneligliptin showed no significant difference in incidences of hypoglycemia and gastrointestinal adverse events (OR [95% CI], 1.30 [0.70 to 2.19] and 1.48 [0.78 to 2.98], respectively), and 40 mg of teneligliptin showed no significant difference in incidence of hypoglycemia (OR [95% CI], 2.63 [0.46 to 8.10]). Generally, antidiabetic effect and hypoglycemia risk of teneligliptin gradually increased as its dose increased from 5 mg to 40 mg. Compared to 20 mg of teneligliptin, 40 mg of teneligliptin showed superior efficacy and no-inferior safety, which was considered as the best option in reducing HbA1c, FPG, and 2h PPG and increasing proportion of the patients achieving HbA1c < 7% (SUCRA, 85.51%, 84.24%, 79.06%, and 85.81%, respectively) among all the included interventions.ConclusionCompared to sitagliptin, vildagliptin, metformin, bromocriptine, and placebo, teneligliptin displayed favorable efficacy and acceptable safety in treating T2DM. Twenty milligrams or 40 mg per day was the optimal dosage regimen of teneligliptin. The results of this study will provide important evidence-based basis for rational use of teneligliptin and clinical decision-making of T2DM medication

Effectiveness and safety of Compound Danshen injection as treatment for pregnancy-induced hypertension: A metaanalysis

Purpose: To systematically evaluate the effectiveness and safety of Compound Danshen injection in patients with pregnancy-induced hypertension (PIH).Methods: PubMed, Embase, Cochrane Library, Chinese biomedical literature database (CBM), VIP (xiAn), China National Knowledge Infrastructure (CNKI) and Wan Fang databases were searched up to March 20, 2018, for all randomized controlled trials (RCTs) on the use of Compound Danshen injection in patients with PIH. Data were extracted from included studies after assessing the quality of literature. Revman 5.3 software was used for statistical analysis．Results: A total of 18 RCTs involving 1735 patients were included. The results of meta-analysis indicated that the study group was superior to the control group in clinical effectiveness (RR = 1.15, 95 % CI: 1.02 - 1.30); intrauterine fetal distress (RR = 0.26, 95 % CI: 0.09 - 0.70); cesarean section (RR = 0.72, 95 % CI: 0.58 - 0.90), and neonatal asphyxia (RR = 0.23, 95 % CI: 0.11 - 0.48). There were no statistical differences in fetal heart rate abnormalities (RR = 0.58, 95 %, CI: 0.33 - 1.02, p > 0.05) and postpartum hemorrhage (RR = 0.86, 95 % CI: 0.53 - 1.42) between the two groups.Conclusion: Treatment of PIH with Compound Danshen injection (alone or in combination) is superior to the use of conventional western medical treatment in safety and effectiveness. However, higher quality clinical studies are needed to confirm these results because most trials included in this study were of low quality.Keywords: Pregnancy-induced hypertension (PIH), Compound Danshen injection, Meta-analysi

A high-precision bidirectional time-transfer system over a single fiber based on wavelength-division multiplexing and time-division multiplexing

In this paper, a high-precision bidirectional time-transfer system over a single fiber based on wavelength-division multiplexing and time-division multiplexing (SFWDM-TDM) is proposed, which combines the advantages of wavelength-division multiplexing and time-division multiplexing. It uses two dense wavelength-division channels to effectively suppress the problem of optical fiber reflection. At the same time, the time-division multiplexing method is used in combination with sampling and holding the time to complete the multi-user task. In hardware, we optimized the carrier processing and the high-precision time-delay control module of the SFWDM-TDM system to complete high-precision time-transfer equipment. In software and algorithm, the optical fiber time-interval measurement method and measurement times are optimized, and the SFWDM-TDM system reaches a synchronization accuracy of 8.9 ps at 1 s. Finally, a real-time detection mechanism with self-recovery ability is added to the system. This lays the foundation for a reliable, long-distance, high-precision, and multi-user mode optical fiber time- and frequency-transfer network

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition