Effect and safety of diluted vasopressin injection on bleeding during robot-assisted laparoscopic myomectomy: a protocol for a randomised controlled pilot trial.

INTRODUCTION: Even though the injection of diluted vasopressin into the uterus is expected to reduce intraoperative bleeding with decreased adverse effects during robot-assisted laparoscopic myomectomy (RALM), there is a lack of relevant trials to show its effect and safety. Thus, this study was designed to compare the effect and safety of vasopressin injection on bleedings based on dilution levels of vasopressin with constant volumes during RALM. METHODS AND ANALYSIS: This is a randomised controlled pilot trial, where a total of 39 patients will be randomly divided into three experimental groups in a 1:1:1 ratio. All patients will be classified into the three groups based on the dilution level of vasopressin: group 1-a solution prepared by mixing 20 units of vasopressin with 100 mL of normal saline to make a total of 100 mL; group 2-a solution prepared by mixing 20 units of vasopressin with 200 mL of normal saline to make a total of 100 mL and group 3-a solution prepared by mixing 20 units of vasopressin with 400 mL of normal saline to make a total of 100 mL. During RALM, we will inject diluted vasopressin at different concentrations with a total of 100 mL. As the primary endpoint, estimated blood loss would be compared. As secondary endpoints, we will check the level of haemoglobin and haematocrit, operation time, amount of transfusion, and the period of hospitalisation. In addition, we will check other complications related to vasopressin injection. ETHICS AND DISSEMINATION: This pilot study has been approved by the Institutional Review Board of the Seoul National University Hospital (No. H-2011-107-1174). All potential subjects will be provided written informed consent. The results of this study will be published in peer-reviewed journals and be presented at academic conferences. TRIAL REGISTRATION NUMBERS: NCT04874246 and CKCT0006225.

Effects of sarcopenia and sarcopenic obesity on joint pain and degenerative osteoarthritis in postmenopausal women.

This study aimed to identify the prevalence of sarcopenia, obesity, and sarcopenic obesity and examine their association with radiographic knee osteoarthritis (OA) and knee pain in Korean postmenopausal women. This cross-sectional study utilized the data from Korean National Health and Nutrition Examination Surveys 2009-2011. The participants were categorized into 4 groups based on body composition: either sarcopenic (appendicular skeletal muscle < 23%) or not, either obese (body mass index ≥ 25.0 kg/m2) or not. The prevalence of radiographic knee OA and knee pain was calculated. The effect of hormone replacement therapy (HRT) was also evaluated. The prevalence of radiographic knee OA, knee pain, and both were all highest in the sarcopenic obese group and lowest in the control group (61.49% vs. 41.54%, 39.11% vs. 27.55%, 32.04% vs. 17.82%, all p < 0.001). Without sarcopenia, obese women showed significantly higher ratio of radiographic knee OA only (57.64% vs. 41.54%, p < 0.001). With sarcopenia, the coexistence of obesity presented higher ratio of radiographic knee OA, knee pain, and both compared to sarcopenia without obesity (61.49% vs. 41.82%, 39.11% vs. 27.61%, 32.04% vs. 17.60%, all p < 0.001). The use of HRT for more than 1 year was not associated with radiographic knee OA, knee pain, or both (p = 0.147, 0.689 and 0.649, respectively). Obesity with sarcopenia had greater effect on knee OA compared to obesity without sarcopenia. Moreover, HRT use for more than 1 year was not associated with the prevalence of knee OA. Therefore, more efforts should focus on reducing body fat and increasing muscle in postmenopausal women with knee OA.

Prognostic value of complete metabolic response on ¹8F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer.

OBJECTIVE: We investigated the prognostic value of complete metabolic response (CMR) on ¹8F-fluorodeoxyglucose positron emission tomography/computed tomography (¹8F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC). METHODS: PET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis. RESULTS: Between 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552-0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542-0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490-0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27-0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05-0.99; p=0.048). CONCLUSION: CMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.

Second-line olaparib maintenance therapy is associated with poor response to subsequent chemotherapy in BRCA1/2-mutated epithelial ovarian cancer: A multicentre retrospective study.

INTRODUCTION: With expanded use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi), there is a potential impact of PARPi resistance on platinum resistance. A post-hoc analysis of SOLO2 demonstrated a reduction in response to subsequent platinum-based therapy among patients who received prior olaparib but not placebo. The present multicentre, retrospective, observational study was conducted to determine the effects of olaparib on subsequent therapy for recurrent epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Data on EOC patients with BRCA1/2-mutated tumours who received second-line platinum-based chemotherapy between January 2012 and June 2020, at three South Korean institutions (n = 197) were collected. Patients who received olaparib as maintenance therapy after second-line chemotherapy were assigned to the olaparib group (n = 105), and subjects who did not receive olaparib maintenance therapy were assigned to the control group (n = 92). The primary endpoint was time intervals from the date of second disease progression (PFS1) to the date of third disease progression (PFS2), expressed as PFS2 - PFS1. RESULTS: As expected, PFS1 in the olaparib group was longer than the control group. However, PFS2 - PFS1 in the olaparib group was significantly shorter than that of the control group (median 7.9 vs. 13.6 m; p = 0.0005). Even when the third-line PARPi maintenance (cross-over) patients were excluded from the control group, the response to subsequent therapy in the olaparib group remained poor (median 7.7 vs. 11.5; p = 0.0422). DISCUSSIONS: Patients with platinum-sensitive BRCA1/2 mutated tumours who progressed during olaparib maintenance after second-line chemotherapy were less likely to respond to third-line chemotherapy compared to controls who did not receive olaparib, suggesting that resistance to olaparib may contribute to chemotherapy resistance.

Comparison of Serum Anti-Mullerian Hormone-Level Changes in Single-Port Laparoscopic Endometriotic and Non-Endometriotic Ovarian Cyst Enucleations.

OBJECTIVES: This study compared serum anti-Mullerian hormone (AMH) levels in endometriotic cysts (ECs) with those in non-ECs and analyzed changes thereof after single-port laparoscopic (SPL) ovarian cyst enucleation using vasopressin injection. METHODS: In total, 180 patients (EC group, n = 112; non-EC group, n = 68) who underwent SPL ovarian cyst enucleation were retrospectively reviewed. Their AMH levels were checked preoperatively, on postoperative day 10 (POD10), and on postoperative month 3 (POM3). Changes in AMH levels were analyzed according to tumor type and vasopressin use. RESULTS: The median initial and postoperative serum AMH levels in the EC group were significantly lower than those in the non-EC group (preoperation: 2.0 vs 3.8 ng/mL, P < 0.001; POD10: 1.0 vs 3.2 ng/mL, P < 0.001; POM3: 1.2 vs 3.6 ng/mL, P < 0.001). The postoperative decrease in AMH levels was higher in the EC group than the non-EC group on POD10 (0.8 vs 0.5 ng/mL, P = 0.011) but not on POM3 (0.7 vs 0.5 ng/mL, P = 0.164). Vasopressin injection during EC enucleation had no significant effect on the decrease in AMH levels on POD10 (vasopressin group vs non-vasopressin group: 1.0 vs 0.8 ng/mL, P = 0.253) and POM3 (vasopressin group vs nonvasopressin group: 1.4 vs 1.1 ng/mL, P = 0.242). CONCLUSIONS: AMH levels were lower at baseline and had higher decreasing rates after SPL surgery in the EC group relative to the non-EC group. Vasopressin injection might not protect the ovary from the postoperative decrease in AMH levels.

Origin of the log-normal popularity distribution of trending memes in social networks.

We study the origin of the log-normal popularity distribution of trending memes observed in many real social networks. Based on a biological analogy, we introduce a fitness of each meme, which is a natural assumption based on sociological reasons. From numerical simulations, we find that the relative popularity distribution of the trending memes becomes a log-normal distribution when the fitness of the meme increases exponentially. On the other hand, if the fitness grows slowly, then the distribution significantly deviates from the log-normal distribution. This indicates that the fast growth of fitness is the necessary condition for the trending meme. Furthermore, we also show that the popularity of the trending topic grows linearly. These results provide a clue to understand long-lasting questions, such as what causes some memes to become extremely popular and how such memes are exposed to the public much longer than others.

Two order parameters for the Kuramoto model on complex networks.

We investigate the behavior of two different order parameters for the Kuramoto model in the desynchronized phase. Since the primary role of the order parameter is to distinguish different phases, we focus on the ability to discern the desynchronized phase from the synchronized one on complex networks with the size N. From the exact derivation of the difference between two order parameters, Δ, on a star network, we find that these order parameters disagree in the desynchronized phase. We also show that the hub plays an important role and provide an analytic conjecture on the condition that the two order parameters agree with each other as N→∞. The conjecture is numerically confirmed.

Network exploration using true self-avoiding walks.

We study the mean first passage time (MFPT) of true self-avoiding walks (TSAWs) on various networks as a measure of searching efficiency. From the numerical analysis, we find that the MFPT of TSAWs, τ^{TSAW}, approaches the theoretical minimum τ^{th}/N=1/2 on synthetic networks whose degree-degree correlations are positive. On the other hand, for biased random walks (BRWs) we find that the MFPT, τ^{BRW}, depends on the parameter α, which controls the degree-dependent bias. More importantly, we find that the minimum MFPT of BRWs, τ_{min}^{BRW}, always satisfies the inequality τ_{min}^{BRW}>τ^{TSAW} on any synthetic network. The inequality is also satisfied on various real networks. From these results, we show that the TSAW is one of the most efficient models, whose efficiency approaches the theoretical limit in network explorations.

Reciprocity in spatial evolutionary public goods game on double-layered network.

Spatial evolutionary games have mainly been studied on a single, isolated network. However, in real world systems, many interaction topologies are not isolated but many different types of networks are inter-connected to each other. In this study, we investigate the spatial evolutionary public goods game (SEPGG) on double-layered random networks (DRN). Based on the mean-field type arguments and numerical simulations, we find that SEPGG on DRN shows very rich interesting phenomena, especially, depending on the size of each layer, intra-connectivity, and inter-connected couplings, the network reciprocity of SEPGG on DRN can be drastically enhanced through the inter-connected coupling. Furthermore, SEPGG on DRN can provide a more general framework which includes the evolutionary dynamics on multiplex networks and inter-connected networks at the same time.

The origin of the criticality in meme popularity distribution on complex networks.

Previous studies showed that the meme popularity distribution is described by a heavy-tailed distribution or a power-law, which is a characteristic feature of the criticality. Here, we study the origin of the criticality on non-growing and growing networks based on the competition induced criticality model. From the direct Mote Carlo simulations and the exact mapping into the position dependent biased random walk (PDBRW), we find that the meme popularity distribution satisfies a very robust power- law with exponent α = 3/2 if there is an innovation process. On the other hand, if there is no innovation, then we find that the meme popularity distribution is bounded and highly skewed for early transient time periods, while it satisfies a power-law with exponent α ≠ 3/2 for intermediate time periods. The exact mapping into PDBRW clearly shows that the balance between the creation of new memes by the innovation process and the extinction of old memes is the key factor for the criticality. We confirm that the balance for the criticality sustains for relatively small innovation rate. Therefore, the innovation processes with significantly influential memes should be the simple and fundamental processes which cause the critical distribution of the meme popularity in real social networks.

Percolation in spatial evolutionary prisoner's dilemma game on two-dimensional lattices.

We study the spatial evolutionary prisoner's dilemma game with updates of imitation max on triangular, hexagonal, and square lattices. We use the weak prisoner's dilemma game with a single parameter b. Due to the competition between the temptation value b and the coordination number z of the base lattice, a greater variety of percolation properties is expected to occur on the lattice with the larger z. From the numerical analysis, we find six different regimes on the triangular lattice (z=6). Regardless of the initial densities of cooperators and defectors, cooperators always percolate in the steady state in two regimes for small b. In these two regimes, defectors do not percolate. In two regimes for the intermediate value of b, both cooperators and defectors undergo percolation transitions. The defector always percolates in two regimes for large b. On the hexagonal lattice (z=3), there exist two distinctive regimes. For small b, both the cooperators and the defectors undergo percolation transitions while only defectors always percolate for large b. On the square lattice (z=4), there exist three regimes. Combining with the finite-size scaling analyses, we show that all the observed percolation transitions belong to the universality class of the random percolation. We also show how the detailed growth mechanism of cooperator and defector clusters decides each regime.

Spatial evolutionary public goods game on complete graph and dense complex networks.

We study the spatial evolutionary public goods game (SEPGG) with voluntary or optional participation on a complete graph (CG) and on dense networks. Based on analyses of the SEPGG rate equation on finite CG, we find that SEPGG has two stable states depending on the value of multiplication factor r, illustrating how the "tragedy of the commons" and "an anomalous state without any active participants" occurs in real-life situations. When r is low (<<), the state with only loners is stable, and the state with only defectors is stable when r is high (>>). We also derive the exact scaling relation for r*. All of the results are confirmed by numerical simulation. Furthermore, we find that a cooperator-dominant state emerges when the number of participants or the mean degree, 〈k〉, decreases. We also investigate the scaling dependence of the emergence of cooperation on r and 〈k〉. These results show how "tragedy of the commons" disappears when cooperation between egoistic individuals without any additional socioeconomic punishment increases.

Complete set of types of phase transition in generalized heterogeneous k-core percolation.

We study heterogeneous k-core (HKC) percolation with a general mixture of the threshold k, with k(min) = 2 on random networks. Based on the local tree approximation, the scaling behaviors of the percolation order parameter P(∞)(p) are analytically obtained for general distributions of the threshold k. The analytic calculations predict that the generalized HKC percolation is completely described by the series of continuous transitions with order parameter exponents ß(n) = 2/n, discontinuous hybrid transitions with ß(H) = 1/2 or ß(A)(4)) = 1/4, and three kinds of multiple transitions. Simulations of the generalized HKC percolations are carried out to confirm analytically predicted transition natures. Specifically, the exponents of the series of continuous transitions are shown to satisfy the hyperscaling relation 2ß(n) + γ(n) = ν(n).

Dimensional dependence of phase transitions in explosive percolation.

To understand the dependence of phase-transition natures in explosive percolations on space dimensions, the number n(cut) of cutting bonds (sites) and the fractal dimension d(CSC) of the critical spanning cluster (CSC) for the six different models introduced in Phys. Rev. E 86, 051126 (2012) are studied on two- and three-dimensional lattices. It is found that n(cut)(L→∞)=1 for the intrabond-enhanced models and the site models on the two-dimensional square lattice with lattice size L. In contrast, n(cut) for the intrabond-suppressed models scales as n(cut)≃L(d(cut)) with d(cut)=1. d(CSC)=2.00(1) is obtained for the intrabond-enhanced models and the site models, while d(CSC)=1.96(1)(<2) is obtained for the intrabond-suppressed models in two dimensions (2D). These results strongly support that the intrabond-enhanced models and the site models undergo the discontinuous transition in 2D, while the intrabond-suppressed models do the continuous transition in 2D. On the three-dimensional cubic lattice, we find that d(cut)>0 and d(CSC)=2.8(1)(<3) for all six models, which indicates that the models undergo the continuous transition. Based on the finite-size scaling analyses of mean cluster size and order parameter, all six models in 3D show nearly the same critical phenomena within numerical errors.

Parallel discrete-event simulation schemes with heterogeneous processing elements.

To understand the effects of nonidentical processing elements (PEs) on parallel discrete-event simulation (PDES) schemes, two stochastic growth models, the restricted solid-on-solid (RSOS) model and the Family model, are investigated by simulations. The RSOS model is the model for the PDES scheme governed by the Kardar-Parisi-Zhang equation (KPZ scheme). The Family model is the model for the scheme governed by the Edwards-Wilkinson equation (EW scheme). Two kinds of distributions for nonidentical PEs are considered. In the first kind computing capacities of PEs are not much different, whereas in the second kind the capacities are extremely widespread. The KPZ scheme on the complex networks shows the synchronizability and scalability regardless of the kinds of PEs. The EW scheme never shows the synchronizability for the random configuration of PEs of the first kind. However, by regularizing the arrangement of PEs of the first kind, the EW scheme is made to show the synchronizability. In contrast, EW scheme never shows the synchronizability for any configuration of PEs of the second kind.

Irreversible bimolecular chemical reactions on directed scale-free networks.

Kinetics of irreversible bimolecular chemical reactions A+A→0 and A+B→0 on directed scale-free networks with the in-degree distribution P(in)(k)∼k(-γ)(in) and the out-degree distribution P(out)(ℓ)∼ℓ(-γ)(out) are investigated. Since the correlation between k and ℓ of each node generally exists in directed networks, we control the correlation (kℓ) with the probability r∈[0,1] by two different algorithms for the construction of the directed networks, i.e., the so-called k and ℓ algorithms. For r=1, the k algorithm gives (kℓ)=(k(2)), whereas the ℓ algorithm gives (kℓ)=(ℓ(2). For r=0, (kℓ)=(k)(ℓ) for both algorithms. The kinetics of both reactions are analyzed using heterogeneous mean-field (HMF) theory and Monte Carlo simulations. The density of particles (ρ) algebraically decays in time t as ρ(t)∼t(-α). The kinetics of both reactions are determined by the same rate equation, dρ/dt=aρ(2)+bρ(θ-1), apart from coefficients. The exponent θ is determined by the algorithm: θ=γ(in) for the k algorithm (r≥0) and θ=γ(min) for the ℓ algorithm (r>0), where γ(min) is the smaller exponent between γ(in) and γ(out). For θ>3, one observes the ordinary mean-field kinetics, ρ∼1/t (α=1). In contrast, for θ<3, ρ(t) anomalously decays with α=1/(θ-2). The HMF predictions are confirmed by the simulations on quenched directed networks.

Phase transitions in paradigm shift models.

Two general models for paradigm shifts, deterministic propagation model (DM) and stochastic propagation model (SM), are proposed to describe paradigm shifts and the adoption of new technological levels. By defining the order parameter m based on the diversity of ideas, Δ, it is studied when and how the phase transition or the disappearance of a dominant paradigm occurs as a cost C in DM or an innovation probability α in SM increases. In addition, we also investigate how the propagation processes affect the transition nature. From analytical calculations and numerical simulations m is shown to satisfy the scaling relation m=1-f(C/N) for DM with the number of agents N. In contrast, m in SM scales as m=1-f(α(a)N).

Epidemic spreading in annealed directed networks: susceptible-infected-susceptible model and contact process.

We investigate epidemic spreading in annealed directed scale-free networks with the in-degree (k) distribution P(in)(k)~k(-γ(in)) and the out-degree (ℓ) distribution, P(out)(ℓ)~ℓ(-γ(out)). The correlation of each node on the networks is controlled by the probability r(0≤r≤1) in two different algorithms, the so-called k and ℓ algorithms. For r=1, the k algorithm gives =, whereas the ℓ algorithm gives =<ℓ(2)>. For r=0, =<ℓ> for both algorithms. As the prototype of epidemic spreading, the susceptible-infected-susceptible model and contact process on the networks are analyzed using the heterogeneous mean-field theory and Monte Carlo simulations. The directedness of links and the correlation of the network are found to play important roles in the spreading, so that critical behaviors of both models are distinct from those on undirected scale-free networks.

Classification of transport backbones of complex networks.

Transport properties in random and scale-free (SF) networks are studied by analyzing the betweenness centrality (BC) distribution P(B) in the minimum spanning trees (MSTs) and infinite incipient percolation clusters (IIPCs) of the networks. It is found that P(B) in MSTs scales as P(B)∼B(-δ). The obtained values of δ are classified into two different categories, δ≃1.6 and δ≃2.0. Using the mapping between BC and the branch size of tree structures, it is proved that δ in MSTs which are close to critical trees is 1.6. In contrast, δ in MSTs which are supercritical trees is shown to be 2.0. We also find δ=1.5 in IIPCs, which is a natural result because IIPC is physically critical. Based on the results in MSTs, a physical reason why δ≥2 in the original networks is suggested.

Bond-site duality and nature of the explosive-percolation phase transition on a two-dimensional lattice.

To establish the bond-site duality of explosive percolations in two dimensions, the site and bond explosive-percolation models are carefully defined on a square lattice. By studying the cluster distribution function and the behavior of the second largest cluster, it is shown that the duality in which the transition is discontinuous exists for the pairs of the site model and the corresponding bond model which relatively enhances the intrabond occupation. In contrast the intrabond-suppressed models which have no corresponding site models undergo a continuous transition and satisfy the normal scaling ansatz as ordinary percolation.