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.

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.

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.

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.

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.

Reaction symmetry of irreversible reaction nA+mB-->0.

We investigate the kinetics of irreversible reaction nA+mB-->0. When nA particles and mB particles encounter on the same site, the reaction takes place. We classify the reaction into two classes, the symmetric and the asymmetric reactions. The symmetric reaction means both nA+mB-->0 and mA+nB-->0, while the asymmetric reaction means only nA+mB-->0 for a given (n,m) pair. The kinetics of the reaction follows the fluctuation-dominated kinetics of A+B-->0 for Nor=Nc, the kinetics follows a mean-field rate equation. For the asymmetric reaction, it was shown that Nc is 5. We numerically show that the reaction symmetry changes Nc in one dimension. We investigate the asymptotic scaling behaviors of density and various lengths characterizing the spatial organization of particles such as domain length and interparticle distance. Lengths exhibit much clear crossover to the mean-field region at the expected Nc of each reaction. From the scaling behavior of density and lengths, we show Nc=4 for the symmetric reaction in one dimension. Therefore the symmetry in the reaction changes the upper critical dimension, which implies that the kinetics cannot be described by a single theory.

Conserved-mass aggregation model with mass-dependent diffusion rate on complex networks.

We investigate the condensation phenomena of conserved-mass aggregation (CA) with mass-dependent diffusion rate on scale-free networks (SFNs). In the model, the mass m of a node isotropically diffuses to one of directly linked nodes with rate D(m)=m(-alpha), where alpha>0. With rate omega , unit mass is chipped from the mass and also isotropically diffuses. It was shown that no condensation phase transitions occur on regular lattices. However, on SFNs with degree distribution P(k) approximately k(-gamma), we show from mean-field approximation that the model exhibits various types of condensation phenomena according to alpha and gamma . There exists crossover alphac=(gamma-2)/(gamma-1) over which a system undergoes the same type of the condensation as that of zero-range process with jumping rate p(m)=mdelta regardless of gamma(>2). We find delta=1-alpha for alphacor=1. For alpha3, a system exhibits the behavior on regular lattice. For gamma

Searching method through biased random walks on complex networks.

Information search is closely related to the first-passage property of diffusing particle. The physical properties of diffusing particle is affected by the topological structure of the underlying network. Thus, the interplay between dynamical process and network topology is important to study information search on complex networks. Designing an efficient method has been one of main interests in information search. Both reducing the network traffic and decreasing the searching time have been two essential factors for designing efficient method. Here we propose an efficient method based on biased random walks. Numerical simulations show that the average searching time of the suggested model is more efficient than other well-known models. For a practical interest, we demonstrate how the suggested model can be applied to the peer-to-peer system.

Conserved-mass aggregation model with mass-dependent fragmentation on complex networks.

We study the conserved-mass aggregation model with mass-dependent fragmentation on random networks (RNs) and scale-free networks (SFNs) with degree distribution Pk approximately k(-gamma). In the model, masses isotropically diffuse with unit rate. With rate omega, a mass m(lambda) is fragmented from a node with mass m , and moves to one of the linked nodes with the equal probability. For lambda=0 , the model is known to undergo the condensation phase transitions at a certain criticality rho(c) . From the mean-field balance equation for an aggregate, we analytically show that the present model exhibits different behavior depending on network structures. The condensation always occurs for lambda<0 . For 03 undergoes the condensation transitions (sharp crossovers) at rho(c) which diverges with network size N as N(lambda). Hence, in the limit N-->infinity , masses uniformly distribute without the condensation (fluid phase). On the other hand, for gamma< or =3 , a crossover lambda(c)=1(gamma-1) exists. The condensation always occurs for lambda or =lambda(c) . The phase separation results from the competition between the heterogeneity of network structure and the enhanced chipping by lambda . We numerically confirm all the predictions.

Condensation phenomena of a conserved-mass aggregation model on weighted complex networks.

We investigate the condensation phase transitions of the conserved-mass aggregation (CA) model on weighted scale-free networks (WSFNs). In WSFNs, the weight w_{ij} is assigned to the link between the nodes i and j . We consider the symmetric weight given by w_{ij}=(k_{i}k_{j});{alpha} . On WSFNs, we numerically show that a certain critical alpha_{c} exists below which the CA model undergoes the same type of condensation transitions as those of the CA model on regular lattices. However, for alpha > or = alpha_{c} , the condensation always occurs for any density rho and omega . We analytically find alpha_{c}=(gamma-3)/2 on the WSFN with the degree exponent gamma . To obtain alpha_{c} , we analytically derive the scaling behavior of the stationary probability distribution P_{k};{infinity} of finding a walker at nodes with degree k , and the probability D(k) of finding two walkers simultaneously at the same node with degree k . We find P_{k};{infinity} approximately k;{alpha+1-gamma} and D(k) approximately k;{2(alpha+1)-gamma} , respectively. With P_{k};{infinity} , we also show analytically and numerically that the average mass m(k) on a node with degree k scales as k;{alpha+1} without any jumps at the maximal degree of the network for any rho as in SFNs with alpha=0 .

Agent-based spin model for financial markets on complex networks: emergence of two-phase phenomena.

We study a microscopic model for financial markets on complex networks, motivated by the dynamics of agents and their structure of interaction. The model consists of interacting agents (spins) with local ferromagnetic coupling and global antiferromagnetic coupling. In order to incorporate more realistic situations, we also introduce an external field which changes in time. From numerical simulations, we find that the model shows two-phase phenomena. When the local ferromagnetic interaction is balanced with the global antiferromagnetic interaction, the resulting return distribution satisfies a power law having a single peak at zero values of return, which corresponds to the market equilibrium phase. On the other hand, if local ferromagnetic interaction is dominant, then the return distribution becomes double peaked at nonzero values of return, which characterizes the out-of-equilibrium phase. On random networks, the crossover between two phases comes from the competition between two different interactions. However, on scale-free networks, not only the competition between the different interactions but also the heterogeneity of underlying topology causes the two-phase phenomena. Possible relationships between the critical phenomena of spin system and the two-phase phenomena are discussed.

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.

Kinetics of the bosonic A+B-->0 reaction with on-site attractive interaction.

We investigate kinetics of the uniformly driven bosonic A+B-->0 reaction with on-site attractive interaction in one dimension. In this model, n(i)(lambda) particles from a site with n(i) particles are driven to the right. When particles of opposite species occupy the same site, the reaction takes place instantaneously. Since n(i)(lambda)

Double domain structure of the pair contact process with diffusion.

We investigate the domain structure of the pair contact process with diffusion (PCPD). PCPD is a stochastic reaction-diffusion model which evolves by the competition of two binary reactions, 2A-->3A and 2A-->0 . In addition, each particle diffuses isotropically, which leads to the bidirectional coupling between solitary particles and pairs. The spreading domain formed from localized activities in vacuum consists of two regions: The coupled region of size R{p} where pairs and solitary particles coexist and the uncoupled region of size R{U} where only solitary particles exist, respectively. The size of the whole domain R is given as R=R{p}+R{U} . At criticality, R{p} and R{U} scale as R{p} approximately t(1/Z{p}) and R{U} approximately t(1/Z{U}) with Z{U}>Z{p}. We estimate Z{p}=1.61(1) and Z{U}=1.768(8) . Hence the correction to the scaling of R,Q=R{U}/R{p} slowly decays extremely, which makes it practically impossible to identify the asymptotic scaling behavior of R. The double domain structure is another reason for the extremely slow approach to the asymptotic scaling regime of PCPD.

Scaling property of flux fluctuations from random walks.

We study dynamical scaling of flux fluctuation sigma(t) from the one-random-walker model on regular lattices and complex networks and compare it to the surface width W(t) of a corresponding growth model. On the regular lattices, we analytically show that sigma(t) undergoes a crossover from the nontrivial scaling regime to the trivial one by increasing time t, and we verify the results by numerical simulations. In contrast to the results on the regular lattices, sigma(t) does not show any crossover behavior on complex networks and satisfies the scaling relation sigma(t) approximately t(1/2) for any t. On the other hand, we show that W(t) of the corresponding model on complex networks has two different scaling regimes, W approximately t(1/2) for t<>N .

Statistical properties of sampled networks by random walks.

We study the statistical properties of the sampled networks by a random walker. We compare topological properties of the sampled networks such as degree distribution, degree-degree correlation, and clustering coefficient with those of the original networks. From the numerical results, we find that most of topological properties of the sampled networks are almost the same as those of the original networks for gamma les approximately <3. In contrast, we find that the degree distribution exponent of the sampled networks for gamma>3 somewhat deviates from that of the original networks when the ratio of the sampled network size to the original network size becomes smaller. We also apply the sampling method to various real networks such as collaboration of movie actor, Worldwide Web, and peer-to-peer networks. All topological properties of the sampled networks are essentially the same as those of the original real networks.

Condensation phase transitions of symmetric conserved-mass aggregation model on complex networks.

We investigate condensation phase transitions of the symmetric conserved-mass aggregation (SCA) model on random networks (RNs) and scale-free networks (SFNs) with degree distribution P(k) approximately k(-gamma). In the SCA model, masses diffuse with unit rate, and unit mass chips off from mass with rate omega. The dynamics conserves total mass density rho. In the steady state, on RNs and SFNs with gamma > 3 for omega is not equal to infinity, we numerically show that the SCA model undergoes the same type of condensation transitions as those on regular lattices. However, the critical line rho(c)(omega) depends on network structures. On SFNs with gamma < or = 3, the fluid phase of exponential mass distribution completely disappears and no phase transitions occurs. Instead, the condensation with exponentially decaying background mass distribution always takes place for any nonzero density. For the existence of the condensed phase for gamma < or = 3 at the zero density limit, we investigate one lamb-lion problem on RNs and SFNs. We numerically show that a lamb survives indefinitely with finite survival probability on RNs and SFNs with gamma > 3, and dies out exponentially on SFNs with gamma< or = 3. The finite lifetime of a lamb on SFNs with gamma < or = 3 ensures the existence of the condensation at the zero density limit on SFNs with gamma < or = 3, at which direct numerical simulations are practically impossible. At omega = infinity, we numerically confirm that complete condensation takes place for any rho > 0 on RNs. Together with the recent study on SFNs, the complete condensation always occurs on both RNs and SFNs in zero range process with constant hopping rate.

Continuously varying exponents in A+B-->0 reaction with long-ranged attractive interaction.

We investigate kinetics of A+B-->0 reaction with long-range attractive interaction V(r) approximately -r(-2sigma) between A and B or with drift velocity v approximately r(-sigma) in one dimension, where r is the closest distance between A and B . It is analytically shown that dynamical exponents for density of particles (rho) and size of domains (l) continuously vary with sigma when sigma < sigma(c) = 1/2 , while that for the distance between adjacent opposite species (l(AB)) varies when sigma < sigma(c)AB = 7/6 . For sigma > sigma(c)AB diffusive motions dominate the kinetics. These anomalous behaviors with the two crossover values of sigma are supported by numerical simulations.

Diffusive capture process on complex networks.

We study the dynamical properties of a diffusing lamb captured by a diffusing lion on the complex networks with various sizes of N. We find that the lifetime {T} of a lamb scales as {T} approximately N and the survival probability S(N-->infinity, t) becomes finite on scale-free networks with degree exponent gamma > 3. However, S(N, t) for gamma < 3 has a long-living tail on tree-structured scale-free networks and decays exponentially on looped scale-free networks. This suggests that the second moment of degree distribution {k2} is the relevant factor for the dynamical properties in the diffusive capture process. We numerically find that the normalized number of capture events at a node with degree k, n(k), decreases as n(k) approximately k(-sigma). When gamma < 3, n(k) still increases anomalously for k approximately kmax, where kmax is the maximum value of k of given networks with size N. We analytically show that n(k) satisfies the relation n(k) approximately {k2}P(k) for any degree distribution P(k) and the total number of capture events Ntot is proportional to {k2}, which causes the gamma -dependent behavior of S(N, t) and {T}.