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Objective We estimate the causal effect of social connectedness (i.e., the frequencies of meeting with friends, relatives, or neighbors) on cognitive function (the Korean version of Mini-Mental State Exam) among Korean older adults.Methods We used longitudinal panel data collected before and during the coronavirus disease-2019 (COVID-19) to set up the fixed (FE) or random effect (RE) models. To overcome omitted variable bias or reverse causality, we used COVID-19 pandemic period as an instrumental variable to estimate the causal effect of social connectedness on cognitive function.Results Social distancing measures during the COVID-19 period decreased social interaction. The results showed that an increase in the frequency of social interaction led an increase in cognitive scores. Specifically, an increase of one unit in the frequency of meeting familiar people increased cognitive scores by 0.1470 and 0.5035 in the RE and FE models, respectively.Conclusion Social distancing policies due to the global pandemic may have increased the risk of social isolation and cognitive decline among older adults. The government and local communities need to increase their effort to develop way to connect adults through the remainder of the pandemic and beyond.

Lysosomes are intracellular acidic organelles with catabolic functions that contribute to the activation of autophagy. Although autophagy abnormality is associated with defects in lysosomal acidification during the progression of nonalcoholic fatty liver disease (NAFLD), the mechanisms of control of lysosomal acidification are not well understood at the molecular level. Thus, we aimed to elucidate the role of the orphan nuclear receptor retinoic acid–related orphan receptor α (RORα) in lysosomal acidification and autophagic flux, particularly in nutrition‐enriched hepatocytes. First, lysosomal acidity was much lower in the hepatocytes obtained from hepatocyte‐specific RORα‐deleted (RORα‐LKO) mice, whereas the infusion of an adenovirus encoding RORα in wild‐type hepatocytes increased lysosomal acidity, as determined by LysoSensor. Second, the lysosomal translocation of the mechanistic target of rapamycin was increased and immature cathepsin D was accumulated in the liver of RORα‐LKO mice. Third, the accumulation of LC3‐II, p62/sequestosome 1 (SQSTM1), and neighbor of BRCA1 gene 1 (NBR1) was increased in the livers of RORα‐LKO mice, indicating an impaired autophagic flux in the livers. Consistently, the number of autolysosomes containing mitochondria and lipid droplets was dramatically reduced in the RORα‐deleted hepatocytes. Finally, we found that RORα induced the transcription of genes involved in lysosomal function, such as Atp6v1g1, a vacuolar H+‐ATPase (v‐ATPase) subunit, which were largely down‐regulated in the livers of mice with high‐fat diet–induced NAFLD and patients with hepatitis. Conclusion: Targeting RORα may be a potential therapeutic strategy to restore lysosomal acidification, which inhibits the progression of NAFLD., We identified a novel function of RORα that enhanced lysosomal acidification and autophagic flux through the transcriptional activation of Atp6v1g1. Thus, targeting RORα may be a potential therapeutic strategy to restore lysosomal acidification, which inhibits the progression of NAFLD.

Background Phosphoenolpyruvate carboxykinase (Pck1) is a key enzyme that catalyzes an irreversible step of hepatic gluconeogenesis; however, the mechanism underlying Pck1 regulation is not fully understood. This study aims to identify a lncRNA that regulates transcription of the Pck1 gene. Methods The precise structures of five different hepatic Ctcflos isotypes were identified through rapid amplification of cDNA ends in the mouse liver. The expression level of hepatic Ctcflos level was determined by PCR and the role of Ctcflos were assessed using antisense oligonucleotides and virus encoding Ctcflos both in vitro and in vivo. The target protein interacted with Ctcflos was identified through RNA pull down assay. Contribution of Ctcflos in glucocorticoid receptor (GR)-mediated Pck1 gene expression was evaluated by chromatin immunoprecipitation, co-immunoprecipitation, in situ proximity ligation assay, and reporter gene analysis. Results A novel lncRNA Ctcflos was identified in the enhancer region of Pck1 gene. Induction of Ctcflos was dependent on the glucocorticoid receptor (GR) in the livers of fasted or dexamethasone-administered mice. Overexpression of Ctcflos by infusion of an adenovirus encoding Ctcflos increased transcript- and protein-level of Pck1, whereas knockdown of Ctcflos using antisense oligonucleotides suppressed. RNA pulldown experiments showed that Ctcflos bound the heterogeneous ribonucleoprotein L (hnRNPL) which interacts with GR. Interestingly, knockdown of hnRNPL upregulated the Pck1 gene. Finally, we found that, in the presence of Ctcflos, the binding between GR and hnRNPL was weakened, whereas the DNA binding of GR was enriched in the Pck1 enhancer region. Conclusions We report the discovery of a novel lncRNA, Ctcflos, that regulates the transcription of Pck1 by modulating GR function. Targeting Ctcflos may provide a new insight into the development of alternative treatments for hyperglycemia by offering specific regulation of hepatic Pck1 gene expression.

Background: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) family is known to function in innate immune system that protects against retrovirus by deaminating cytosine to uracil in single-stranded DNA. APOBEC family has emerged as an endogenous mutator to contribute to the mutation burden in many cancers. We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA and APOBEC3A-3B deletion polymorphism in Korean breast cancer patients and investigate the correlation between their expression and clinicopathological characteristics. Methods: One hundred thirty-eight patients who underwent surgery for breast cancer in Uijeongbu St. Mary's Hospital between January 2013 and December 2016 were evaluated. RNA and DNA were extracted from 138 breast cancer tissues and 10 adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using real-time quantitative PCR. Insertion and deletion PCR assays were performed to detect the APOBEC3A-3B deletion allele. Mutation hotspots in exon 2-11 of TP53 and exon 9/20 of PIK3CA were evaluated using direct sequencing method. Results: The expression of A3B was increased in breast cancer tissues than in normal breast tissues. The median A3B mRNA expression levels in both triple-negative breast cancer and human epidermal growth factor 2-positive breast cancer were significantly higher than in hormone receptor-positive breast cancer. Old age and high ki-67 expression were associated with increased expression of A3A and A3B. Advanced stage, presence of lymph node involvement, and high histological grade were associated with increased expression of A3A. The APOBEC3B deletion allele was found in 78 (56%) tumor samples. There was no significant association between A3A, A3B mRNA levels and the presence of APOBEC3B deletion allele. There was no difference in clinicopathological characteristics according to the presence of APOBEC3B deletion allele except histological grade. The frequency of high histological grade was significantly higher in tumors with APOBEC3B deletion allele than tumors without APOBEC3B deletion allele. TP53 mutations were identified in 12 (8.7%) cases and PIK3CA mutations were identified in 31 (22.5%) cases. There were no significant differences in the levels of A3A and A3B mRNA expression by TP53 mutation status. The presence of a PIK3CA mutation was significantly associated with lower A3A expression. Conclusions: The levels of A3B mRNA expression showed a difference according to breast cancer subtype, and triple-negative breast cancer showed the highest levels of A3B mRNA expression. The high levels of A3A and A3B mRNA expression were associated with an aggressive phenotype including high proliferation index. The APOBEC3A-3B deletion polymorphism was found in about half of the patients, but there was no difference in clinicopathological factors according to the presence of APOBEC3B deletion allele except histological grade. Citation Format: Won HS, Sun DS, Ko YH, You SH, Kim YS, Kim JS. Clinical implication of APOBEC3A and 3B in Korean patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-05-03.

This abstract was not presented at the conference. Citation Format: Lee S, Ahn SH, Lee JW, Chung IY, Ko BS, Kim HJ, Kim J, Shon G, Son BH. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-21.

This study evaluated the effects of a nonwoven polypropylene (NPP) covering during overwintering with different mulch types and transplant times on bulb onion growth and yield of intermediate-day onions (Allium cepa L.) during the 2015/2016 and 2016/2017 growing seasons. Field experiments were conducted using a split-split plot design with three replicates. Treatments included main plots containing different mulch types (transparent plastic mulch, black plastic mulch, or bare ground), subplots with different transplanting times (20 Oct., 5 Nov., and 20 Nov.), and sub-subplots containing two onion cultivars (Sunpower and Katamaru). NPP was used to cover all plots on 1 Dec., and it was removed on 28 Feb. Mean daily air temperatures during transplanting and root establishment were 2.6 °C higher during the 2015/2016 growing season compared with the 2016/2017 season. NPP covering on bare ground increased soil temperature by 2.1 °C compared with no treatment. Soil water potential with transparent and black mulches and NPP continued to be more than −10 kPa until early March. Number of leaves, and root and leaf weight were significantly greater during the 2015/2016 growing season than during the 2016/2017 growing season; there were also significantly greater for onion plants grown with transparent plastic mulch than for those grown with black plastic mulch or no mulch on 4 Apr. and 5 May. Marketable bulb yield was lower during 2015/2016 (32.0 Mg·ha−1) than during 2016/2017 (38.5 Mg·ha−1); this was due to the increased unmarketable bulb yield, with 33.2 Mg·ha−1 bolters and 3.9 Mg·ha−1 doubled bulbs during 2015/2016 compared with 3.9 Mg·ha−1 bolters and 0.3 Mg·ha−1 doubled bulbs during 2016/2017. Marketable bulb yield of ‘Katamaru’ (38.9 Mg·ha−1) was greater than that of ‘Sunpower’ (31.6 Mg·ha−1). Marketable bulb yield increased with later transplanting times, and onions grown with black plastic mulch achieved the highest bulb yield (43.0 Mg·ha−1), followed by transparent mulch (34.7 Mg·ha−1) and no mulch (28.0 Mg·ha−1). When the temperatures from early November to early December were similar to the 30-year average temperatures, marketable bulb yield could increase with the NPP covering, especially for onions grown with black plastic mulch or no mulch when transplanted from late October to early November.

Background Clinical outcomes after catheter ablation (CA) or pacemaker (PM) implantation for tachycardia-bradycardia syndrome (TBS) has not been well evaluated. Purpose This randomized controlled study compared the efficacy and safety outcomes of CA and PM implantation as an initial treatment for TBS with paroxysmal atrial fibrillation (AF). Methods A total of 70 patients with paroxysmal AF and TBS (mean 64 years, 64.3% male) underwent randomization, and received CA (CA group, n=35) or PM (PM group, n=35) as an initial treatment. The primary outcome was unexpected emergency room visit or hospitalization from any cardiovascular causes. Results The two groups were well-balanced with respect to the baseline characteristics except for difference in age (61.0±8.0 vs. 66.2±7.2, P=0.005). In the intention-to-treatment analysis, the rate of primary outcome was not significantly different between two groups at 2-years of follow-up (19.8% vs. 24.2%; HR 1.25, 95% CI 0.42–3.73, P=0.684). The same trend was noted when the result was adjusted for age (HR 1.16 95% CI 0.26–2.89, P=0.807). The rate of recurrent AF was significantly lower in CA group compared to PM group (24.0% vs. 100% at 2-yreas, P0.99). Conclusion In this randomized controlled study, CA was associated with a similar efficacy and safety with higher rate of sinus rhythm maintenance. CA could be considered a preferable treatment option over PM implantation in patients with paroxysmal AF and TBS. Funding Acknowledgement Type of funding source: None

In this study, a multi-period model of an organic waste-to-biodiesel phased supply chain network is developed to strategically consider variations in the biodiesel demand and the organic waste usage over a long-term planning interval. The proposed model can facilitate planning to determine the biorefinery location and the amount of biodiesel to produce, transport, or utilize to reduce the total cost of the organic waste-to-biodiesel supply chain network design while meeting the biodiesel demand during each period of the planning interval. The features and capabilities of the model are validated by application of a future organic waste-to-biodiesel supply chain network design in South Korea. The optimization results illustrate that the average total annual cost of the organic waste of biodiesel based on the multi-period model will be $US 4.2 billion per year during the period 2020–2030. The minimum selling prices for the optimal network design were determined ranged from $US 3.154–3.156/gallon of biodiesel containing 3% butanol derived from organic waste combined with diesel. A small portion (4.9–6.6%) of the total biodiesel demand was produced from organic waste because of low organic waste availability in the existing anaerobic digestion facilities, leading to increasing the outsourcing costs of butanol. The proposed approach will facilitate the strategic development of a sustainable supply chain network for organic waste recycling for material and energy valorization.

Summer mortality, caused by thermal conditions, is the biggest threat to abalone aquaculture production industries. Various measures have been taken to mitigate this issue by adjusting the environment; however, the cellular processes of Pacific abalone (Haliotis discus hannai) have been overlooked due to the paucity of genetic information. The draft genome of H. discus hannai has recently been reported, prompting exploration of the genes responsible for thermal regulation in Pacific abalone. In this study, 413 proteins were systematically annotated as members of the heat shock protein (HSP) super families, and among them 26 HSP genes from four Pacific abalone tissues (hemocytes, gill, mantle, and muscle) were differentially expressed under cold and heat stress conditions. The co-expression network revealed that HSP expression patterns were tissue-specific and similar to those of other shellfish inhabiting intertidal zones. Finally, representative HSPs were selected at random and their expression patterns were identified by RNA sequencing and validated by qRT-PCR to assess expression significance. The HSPs expressed in hemocytes were highly similar in both analyses, suggesting that hemocytes could be more reliable samples for validating thermal condition markers compared to other tissues.

Mesoporous architectures are remarkable electrode materials for energy storage system due to their large number of active sites and high surface area. Here we report, mesoporous MoS2 particles (pore diameter 34.04 nm) well attached to the surface of thin layered reduced graphene oxide (rGO) via an ultrasonic chemical method for supercapacitor applications. The rGO not only increases the conductivity of MoS2 but also provides a substrate for the attachment of MoS2 with low aggregation. The porous MoS2 provides a large surface area and sufficient way for the fast transport of electrolyte ions toward electrode materials. As a result, the synthesized MoS2/rGO composites exhibited excellent electrochemical performance with a specific capacitance 314.5 F/g in 2M KOH aqueous solution at a scan rate of 10 mV/s and excellent specific capacitance retention (80.02%) after 1000 cycles in a three electrode system for energy storage applications.

This paper presents a bio-based process for the catalytic conversion of cellulose to ethyl levulinate and an analysis of its techno-economic feasibility. The said bio-based process relies as major feedstock on cellulose, which can be derived from lignocellulosic biomass. cellulose is converted to ethyl levulinate via a homogeneous catalytic reaction whereby dilute sulfuric acid in combination with Al salts is the catalyst and ethanol is the solvent and reactant. This approach affords high ethyl levulinate yields but requires complex procedures for used catalyst and solvent recycling. Based on experimental results on the homogeneous catalytic reaction and vapor–liquid equilibrium separation in the previous studies, a simulation was conducted that included process design, energy integration, and economic analysis. Results from this simulation indicated the proposed bio-based process to afford a minimum selling price of US$ 2,830 per ton of ethyl levulinate, which was highly dependent on an off-site supply of heating energy required for ethanol purification. 1

The occurrence of accidents at container ports results in damages and economic losses in the terminal operation. Therefore, it is necessary to accurately predict accidents at container ports. Several machine learning models have been applied to predict accidents at a container port under various time intervals, and the optimal model was selected by comparing the results of different models in terms of their accuracy, precision, recall, and F1 score. The results show that a deep neural network model and gradient boosting model with an interval of 6 h exhibits the highest performance in terms of all the performance metrics. The applied methods can be used in the predicting of accidents at container ports in the future.

Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant inherited disease caused by mutations of the human gap junction alpha 1 gene, which encodes the protein Connexin-43. Patients with ODDD may present with neurological deficits with a typical pleiotropic combination of characteristic craniofacial, ophthalmological, phalangeal, and dental anomalies. In this report, we describe the first genetically confirmed Korean ODDD patient, who presented with spastic paraparesis. We will also review the neurological aspects of ODDD as reported in the literature.

Background Incidence and outcomes of new-onset ventricular tachycardia (VT) after cardiac surgery are not fully evaluated. Purpose We retrospectively analyzed the occurrence of new-onset VTs after cardiac surgery, and their implications on short and long-term mortality. Methods Data of 11,004 adult patients who underwent cardiac surgery at our center from 2006 to 2016 were analyzed. VT was diagnosed when 3 or more consecutive wide QRS complexes (>100 bpm) were documented on ECG. The major study outcomes were in-hospital and 5-years overall mortality rates. Results During index hospitalization for cardiac surgery, clinical VTs were documented in 184 patients (1.7%), which included 74 sustained VTs (SusVT, ≥30 seconds) and 110 non-sustained VTs (NSVT). Those patients with SusVT and NSVT showed higher in-hospital mortality compared to those without VTs (31.1% vs. 24.5% vs. 2.0% for SusVT, NSVT, and no VT, respectively, P24 hours apart from initial episode) were at higher 5-years mortality rate compared to those without (40.7% vs. 15.8%, P=0.018). Conclusion Patients with SusVT and NSVT were at higher risk of in-hospital mortality, and patients with SusVT were associated with higher risk of long-term mortality. The mortality risk was even higher in those with recurrent episodes of VTs. Acknowledgement/Funding None

Background Gender difference in stroke risk by the presence of atrial fibrillation was not well evaluated. Purpose We hypothesized that the gender showed different impacts on future thromboembolic risk in patients with and without atrial fibrillation. Methods The study population comprised of 26,226 patients (mean 56.3 years old, 52.6% male) with (n=3147, 12.0%) or without (n=23079, 88.0%) atrial fibrillation who underwent cardiac evaluations consisted of electrocardiography, echocardiography, and holter monitoring in our center. The main study outcomes were thromboembolic events defined as composite of ischemic stroke and systemic embolism. Results During mean follow-up period of 2.8 years, thromboembolic event occurred in 610 patients (2.3%). In the overall population, the 3-year rate of thromboembolic event of female patients was lower than males (2.2% vs. 2.8%, P=0.011). However, when the population was divided according to the presence of AF, females showed higher rate of thromboembolic events in those with AF (6.7% vs 3.1%, P Conclusion Female gender demonstrated differential thromboembolic risk according to the presence of AF. Acknowledgement/Funding None

Background Radiofrequency catheter ablation (RFCA) for accessory pathways (APs) at the site of prior valve surgery remains challenging. We aimed to clarify the factors associated with successful RFCA for such APs. Methods Upon reviewing a RFCA registry and previous case reports, we included nine patients who underwent RFCA of APs at the site of prior valve surgery (total-VS group; age, 34.0 [24.5–45.0] years; men, 4/9) and 196 patients who underwent RFCA of APs with no history of valve surgery (no-VS group; age, 40.5 [23.0–54.0] years; men, 114/196). Electrophysiological features, procedural details, and outcomes were examined. Results AP exhibited decremental conduction in four of nine patients in the total-VS group. The number of RFCA attempts was significantly higher in the total-VS group than in the no-VS group (10.0 [4.5–14.5] vs 2.0 [1.0–3.0]; p Stepwise approach to AP at valve surgery Conclusions Successful RFCA of APs at the site of prior valve surgery can be achieved by detailed mapping of the areas both above and below the prosthetic valve, as well as by ensuring effective radiofrequency energy delivery using various catheter approaches and RFCA techniques.

Purpose Thromboembolic risk of atrial fibrillation (AF) in heart failure with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) is not well identified. This study assessed the thromboembolic risk of AF in patients with HFpEF, HFmrEF and HFrEF. Materials and methods Within the CODE-AF prospective, outpatient registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation), a total of 10476 patients with non-valvular AF including 929 (8.8%) patients with HF was analyzed. Multivariable cox regression was used to evaluate the risk of thromboembolic event, including stroke, systemic embolism and transient ischemic attack. Hazard ratio (HR) was adjusted by each component of CHA2DS2-VASc risk score and the use of oral anticoagulant (OAC). Results The median age of the overall population was 68.0 (interquartile range, 60.0–75.0); 63.9% were male. The proportion of HFpEF, HFmrEF and HFrEF was 43.6%, 26.7% and 29.7%, respectively. CHA2DS2-VASc risk score was higher in HF group than no-HF group. OAC was more commonly used in HF group than no-HF group (85.2% vs. 68.9%, p Conclusion In OAC-naïve non-valvular AF, HF was associated with increased risk of thromboembolic event. Among 3 types of HF, HFrEF increased the risk of thromboembolic event, while HFmrEF or HFpEF did not. However, in patients with optimal OAC, even HFrEF was not associated with increased risk of thromboembolic event. These results support current OAC strategy in HF patients, especially emphasizing optimal OAC in HFrEF population. Acknowledgement/Funding The National Research Foundation of Korea

Acute liver failure (ALF) is characterized by loss of liver function in response to sustained augmentation of the acute-phase response (APR) in the liver, which can progress even to death. Although the inflammatory interleukin-6 (IL-6)–axis is a crucial factor that drives the hepatic APR by releasing diverse acute-phase proteins (APPs), therapeutic strategies to block the IL-6–STAT3-mediated APR are not well developed. Here, we show that the nuclear receptor retinoic acid-related orphan receptor α (RORα) limits APR-mediated liver injury by inhibiting the hepatic IL-6–STAT3 signaling pathway. Administration of JC1-40, an RORα activator, diminished diethylnitrosamine-induced acute liver injury and repressed transcriptional expression of APPs such as CXCL1 and LCN2 in mice. IL-6-mediated activation of STAT3 was repressed after RORα activation by either adenoviral infusion of RORα or JC1-40 treatment in primary hepatocytes. Activation of RORα decreased transcriptional expression of IL-6 receptor α, an upstream activator of STAT3, both in vitro and in vivo. This may be one mechanism underlying the RORα-mediated inhibition of STAT3. Taken together, our results suggest that RORα is a regulator of the hepatic IL-6–STAT3 signaling pathway and may be a new therapeutic target for treating APR-associated inflammatory ALF.

The aim of this study was to examine the correlation between the tongue coating thickness (TCT) and ultraviolet (UV) fluorescence and propose a new method for the estimation of TCT using a computerized tongue image acquisition system (CTIS). In this prospective and observational single-center study, we acquired tongue images under visible light and near-UV light for 60 patients with functional dyspepsia. Tongue images were acquired twice within a 30-minute interval to assess the reliability of CTIS. Then, the tongue coating was scraped and weighed to derive the wet weight of the tongue coating (WWTC). The percentage of the tongue coating area was calculated from the tongue images acquired under visible light. Mean color values (mCVs) for the UV fluorescence of the dorsal surface of the tongue were also computed. The reliabilities of the derived mCVs and percentage of the tongue coating area were acceptable (intraclass correlation coefficients, 0.907–0.947). The mCVs were more strongly correlated with WWTC than with the area, with mCV of modified lightness showing the strongest association (r = 0.785, P

Retinoic acid-related orphan receptor α (RORα) is considered a key regulator of polarization in liver macrophages that is closely related to nonalcoholic steatohepatitis (NASH) pathogenesis. However, hepatic microenvironments that support the function of RORα as a polarity regulator were largely unknown. Here, we identified maresin 1 (MaR1), a docosahexaenoic acid (DHA) metabolite with a function of specialized proresolving mediator, as an endogenous ligand of RORα. MaR1 enhanced the expression and transcriptional activity of RORα and thereby increased the M2 polarity of liver macrophages. Administration of MaR1 protected mice from high-fat diet-induced NASH in a RORα-dependent manner. Surprisingly, RORα increased the level of MaR1 through transcriptional induction of 12-lipoxygenase (12-LOX), a key enzyme in MaR1 biosynthesis. Furthermore, we demonstrated that modulation of 12-LOX activity enhanced the protective function of DHA against NASH. Together, these results suggest that the MaR1/RORα/12-LOX autoregulatory circuit could offer potential therapeutic strategies for curing NASH.

In the Internet-of-Things (IoT) environments, the publish (pub)/subscribe (sub)-operated communication is widely employed. The use of pub/sub operation as a lightweight communication protocol facilitates communication among IoTs. The protocol consists of network nodes functioning as publishers, subscribers, and brokers, wherein brokers transfer messages from publishers to subscribers. Thus, the communication capability of the broker is a critical factor in the overall communication performance. In this study, multi-agent reinforcement learning (MARL) is applied to find the best combination of broker nodes. MARL goes through various combinations of broker nodes to find the best combination. However, MARL is inefficient to perform with an excessive number of broker nodes. Delaunay triangulation selects candidate broker nodes among the pool of broker nodes. The selection process operates as a preprocessing of the MARL. The suggested Delaunay triangulation is improved by the custom deletion method. Consequently, the two-stage hybrid approach outperforms any methods employing single-agent reinforcement learning (SARL). The MARL eliminates the performance fluctuation of the SARL caused by the iterative selection of broker nodes. Furthermore, the proposed approach requires a fewer number of candidate broker nodes and converges faster.