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Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs), here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and it is the hepatic manifestation of metabolic syndrome (MetS). We aimed to estimate the prevalence of NAFLD defined by the fatty liver index (FLI), in order to investigate the association between FLI and metabolic disorders and to determine the cutoff value of FLI to screen for MetS. This study utilized a national representative sample of Korean adults (the Korean National Health and Nutrition Examination Surveys) which was conducted in 2010-2011. A total of 10,107 adults aged 19 years or older were selected. NAFLD was diagnosed on the basis of an increased FLI (≥60) after the exclusion of alcohol or viral liver disease. NAFLD was identified in 1,134 subjects (age-standardized prevalence, 10.0%). When subjects were categorized into three groups by FLI (<20, 20-59, and ≥60), the higher FLI group showed a higher prevalence of hypertension (49.7% vs 14.4%), diabetes mellitus (DM; 20.4% vs 3.8%), and MetS (74.9% vs 7.4%). FLI was positively associated with age, body mass index, blood pressure, hemoglobin A1c, and homeostasis model assessment of insulin resistance ( for trend <0.001). In the multivariate analysis, the higher FLI group had a significantly higher risk for hypertension (OR =2.92, 95% CI =2.18-3.90, <0.001), DM (OR =4.38, 95% CI =2.96-6.49, <0.001), and MetS (OR =24.85, 95% CI =17.33-35.64, <0.001). However, no increase was observed for cardiovascular disease after adjustment of other risk factors. The cutoff value of the FLI estimated to predict the presence of MetS was 20 (area under the curve 0.849, sensitivity 0.828, and negative predictive value 91.9%). NAFLD prevalence using FLI is significantly higher in subjects with metabolic disorder including MetS. FLI might be a useful screening tool to detect subjects who may require early management of MetS and who have a high cardiovascular risk.

Background: Compared to acute postsurgical pain, studies regarding the role of ketamine in persistent postsurgical pain (PPSP) are limited. Objectives: The aim of this clinical trial was to test if intraoperative low-dose ketamine without postoperative infusion would reduce PPSP development after breast cancer surgery. Study design: We used a randomized, double-blinded, placebo study design. Setting: This study was conducted at Pusan National University Hospital, Republic of Korea, between December 2013 and August 2016. Methods: A total of 184 patients scheduled for breast cancer surgery were randomly assigned to either the control or ketamine group. Before skin incision, a bolus (0.5 mg/kg of ketamine or placebo), followed by a continuous infusion (0.12 mg/kg/h of ketamine or placebo), was administered until the end of the surgery. The patients were interviewed via telephone 1, 3, and 6 months after surgery. The first question was whether the patient had surgery-related pain. If answered affirmatively, questions from the Numeric Rating Scale for pain at rest (NRSr) and for coughing (NRSd) were also asked. Our primary outcome was the incidence of PPSP at 3 months after surgery. Results: For PPSP analysis, 168 patients were included. The number of patients who experienced pain was significantly lower in the ketamine group at 3 months (86.9% in the control group vs 69.0% in the ketamine group, P = .005) postoperatively. However, the NRSr and NRSd did not differ between the groups throughout the follow-up. Limitations: There were no postoperative low-dose ketamine infusion groups to compare due to hospital regulations. Dosage of ketamine was too low to reduce the severity of PPSP. And by using propofol and remifentanil for anesthesia, different results can be deduced with volatile anesthetics. Data from written questionnaires would have been more specific than telephone interviews for long-term assessment. Conclusions: Though intraoperative low-dose ketamine without postoperative infusion significantly reduced the incidence of PPSP up to 3 months after breast cancer surgery, it failed to reduce clinically significant PPSP and improve patients’ quality of life. Key words: Analgesia, breast cancer, chronic pain, ketamine, mastectomy, morphine, pain, postoperative, propofol

Muscles play an important role in energy metabolism. Several studies have investigated the association between muscle mass and metabolic syndrome (MetS), reporting conflicting results. However, studies concerning the association between muscle strength and MetS are limited. We aimed to investigate the association between relative handgrip strength (HGS) and MetS in Korean adults. We analyzed data from 5,014 Korean adults aged ≥20 years (2,472 men and 2,542 women) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2014-2015). The increasing quartiles of relative HGS (defined as the sum of both hands' HGS divided by body mass index) were inversely associated with the risk of MetS in both men and women (OR, 0.37; 95% CI, 0.30-0.45, vs OR, 0.19; 95% CI, 0.14-0.27, respectively) after multivariable adjustment for age, region of residence, smoking status, heavy alcohol consumption, regular exercise, family income, and education level. On multivariable logistic regression analyses, participants with the highest relative HGS had a significant decrease in relative risk of MetS, compared with those with the lowest relative HGS. The multivariable-adjusted ORs (with 95% CIs) for MetS in quartiles 1, 2, 3, and 4 were 1.00, 0.72 (0.55-0.94), 0.34 (0.26-0.46), and 0.22 (0.15-0.32) in men and 1.00, 0.50 (0.36-0.68), 0.26 (0.17-0.40), and 0.16 (0.09-0.27) in women, respectively. Relative HGS showed a highly significant inverse association with the risk of MetS in Korean adults, and it can be a novel biomarker for assessing the risk of MetS.

The cardiovascular (CV) benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) are well established, but their effects on lower limb events (LLEs) remain inconclusive, with conflicting findings from clinical trials and real-world studies. This study aimed to assess the risks of CV and LLEs associated with SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes. The study included patients with type 2 diabetes who were newly prescribed SGLT2i or DPP-4i using data from the National Health Insurance Service in South Korea. A 1:1 propensity score matching method was used to assign 97,584 patients to the SGLT2i and DPP-4i groups. The study endpoints included all-cause mortality, CV events, and LLEs-a composite outcome encompassing diabetic foot or ulcer, amputation, debridement, graft transplantation or flap operation, and revascularization. Over a median follow-up of 2.74 years, the SGLT2i group had a lower incidence of all-cause mortality (hazard ratio [HR] 0.63, 95% CI 0.51-0.78), heart failure (HR 0.85, 95% CI 0.78-0.93), ischemic stroke (HR 0.77, 95% CI 0.67-0.88), and peripheral artery disease (HR 0.66, 95% CI 0.63-0.69) than the DPP-4i group. However, no significant difference was observed in the incidence of myocardial infarction (HR 1.06, 95% CI 0.87-1.28) or LLEs (HR 1.05, 95% CI 0.80-1.38) between the two groups. In this nationwide, real-world study, SGLT2i use demonstrated a neutral effect on LLEs compared to DPP-4i in patients with type 2 diabetes. However, SGLT2i was associated with a lower risk of all-cause mortality, heart failure, ischemic stroke, and peripheral artery disease. These findings contribute to the ongoing debate on the safety of SGLT2i regarding LLEs and highlight their broader CV benefits, warranting further investigation into their long-term effects on lower limb complications.

This study investigated the safety and efficacy of MR-MC-01, a mesenchymal stem cell therapy derived from human embryonic stem cells, in patients with interstitial cystitis (IC), particularly those with Hunner lesions unresponsive to pentosan polysulfate sodium (PPS). Conducted as a prospective, randomized, double-blind, placebo-controlled phase I/IIa clinical trial, it enrolled 22 patients, with six completing phase I and 16 participating in phase IIa. Phase I tested 2 doses (2.0 × 107 and 5.0 × 107 cells) to determine the maximum tolerated dose (MTD), revealing no dose-limiting toxicities and only mild adverse events such as transient hemorrhage and bladder pain. In phase IIa, 12 participants received the MTD of 5.0 × 107 cells, and 4 received placebo. Significant reductions in interstitial cystitis questionnaire (ICQ) and pain urgency frequency (PUF) scores were observed in the treatment group. Improvements were noted in nocturnal voiding frequency and Hunner lesion size, with 8 patients showing either a reduction or complete resolution of lesions after 6 months. The global response assessment (GRA) reported moderate to marked improvement in 41.67% of treated patients versus 25% in the placebo group. MR-MC-01 demonstrated no serious drug-related adverse events, highlighting its favorable safety profile. These findings suggest that MR-MC-01 not only alleviates symptoms but also promotes structural recovery in IC, making it a promising treatment option. Further large-scale, long-term studies are warranted to confirm these results and optimize therapeutic protocols. (Identifier: NCT04610359)

Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels. Our analysis revealed a mechanism of Orai gating by STIM binding to the intracellular 2–3 loop of Orai in C. elegans that is radically different from Orai gating by STIM binding to the N and C termini of Orai in mammals. In addition, we found that the conserved hydrophobic amino acids in the 2–3 loop of Orai1 are important for the oligomerization and gating of channels and are regulated via an intramolecular interaction mechanism mediated by the N and C termini of Orai1. This study identifies a previously unknown SOCE mechanism in C. elegans and suggests that, while the STIM–Orai interaction is conserved between invertebrates and mammals, the gating mechanism for Orai channels differs considerably.

Serum cystatin C has been known as a novel marker of preclinical renal dysfunction, and higher cystatin C levels are associated with increased risks of hip and nonvertebral fractures. However, there are few reports on the association between serum cystatin C and bone mineral density (BMD), especially in the Asian population. We evaluated the association between cystatin C levels and BMD of the spine and hip in Korean adults. A cross-sectional study was performed in 865 Korean adults (325 men and 540 women) who participated in a comprehensive medical examination program and underwent bone densitometry. Renal function was assessed by the estimated glomerular filtration rate (eGFR), which was calculated using an equation based on creatinine (eGFRcre) and cystatin C (eGFRcys). The serum cystatin C level was negatively correlated with different types of BMD, including the lowest lumbar, total lumbar, femoral neck, and total femur BMD, in women, but not in men. Higher cystatin C levels were associated with a higher prevalence of osteoporosis in women (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.69-8.03; =0.001), but not in men (OR, 0.85; 95% CI, 0.30-2.38; =0.761). However, this association was attenuated in the multivariable model adjusted for age, body mass index, serum 25-hydroxyvitamin D , and creatinine (OR, 1.01; 95% CI, 0.38-2.71) in women. In addition, the eGFRcys showed a stronger positive correlation with BMD than the eGFRcre. Our findings suggest that serum cystatin C levels might help identify women with osteoporosis who are susceptible to fractures.