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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.

The triple networks, namely the default-mode network (DMN), the central executive network (CEN), and the salience network (SN), play crucial roles in disorders of the brain, as well as in basic neuroscientific processes such as mindfulness. However, currently, there is no consensus on the underlying functional features of the triple networks associated with mindfulness. In this study, we tested the hypothesis that (a) the partial regression coefficient (i.e., slope): from the SN to the DMN, mediated by the CEN, would be one of the potential mindfulness features in the real-time functional magnetic resonance imaging (rtfMRI) neurofeedback (NF) setting, and (b) this slope level may be enhanced by rtfMRI-NF training. Sixty healthy mindfulness-naïve males participated in an MRI session consisting of two non-rtfMRI-runs, followed by two rtfMRI-NF runs and one transfer run. Once the regions-of-interest of each of the triple networks were defined using the non-rtfMRI-runs, the slope level was calculated by mediation analysis and used as neurofeedback information, in the form of a thermometer bar, to assist with participant mindfulness during the rtfMRI-NF runs. The participants were asked to increase the level of the thermometer bar while deploying a mindfulness strategy, which consisted of focusing attention on the physical sensations of breathing. rtfMRI-NF training was conducted as part of a randomized controlled trial design, in which participants were randomly assigned to either an experimental group or a control group. The participants in the experimental group received contingent neurofeedback information, which was obtained from their own brain signals, whereas the participants in the control group received non-contingent neurofeedback information that originated from matched participants in the experimental group. Our results indicated that the slope level from the SN to the DMN, mediated by the CEN, was associated with mindfulness score (rtfMRI-NF runs: r = 0.53, p = 0.007; p-value was corrected from 10,000 random permutations) and with task-performance feedback score (rtfMRI-NF run: r = 0.61, p = 0.001) in the experimental group only. In addition, during the rtfMRI-NF runs the level of the partial regression coefficient feature was substantially increased in the experimental group compared to the control group (p < 0.05 from the paired t-test; the p-value was corrected from 10,000 random permutations). To the best of our knowledge, this is the first study to demonstrate a partial regression coefficient feature of mindfulness in the rtfMRI-NF setting obtained by triple network mediation analysis, as well as the possibility of enhancement of the partial regression coefficient feature by rtfMRI-NF training. •Mediation analysis using triple networks was employed to estimate functional feature of mindfulness (MF).•Real-time fMRI (rtfMRI) neurofeedback (NF) training based on this functional feature of MF was presented.•The partial regression coefficient from the SN to the DMN, mediated by the CEN appeared to be a potential feature of MF.•The validity of this functional feature of MF was evaluated by comparing alternative functional connectivity levels in the triple networks.•The possibility of enhancement of this functional feature of MF was demonstrated via rtfMRI-NFbased training.

Currently available therapeutic options for non-insulin-dependent diabetes mellitus, such as dietary modification, oral hypoglycemics, and insulin, have limitations of their own. Many natural products and herbal medicines have been recommended for the treatment of diabetes. The present paper reviews medicinal plants that have shown experimental or clinical antidiabetic activity and that have been used in traditional systems of medicine; the review also covers natural products (active natural components and crude extracts) isolated from the medicinal plants and reported during 2001 to 2005. Many kinds of natural products, such as terpenoids, alkaloids, flavonoids, phenolics, and some others, have shown antidiabetic potential. Particularly, schulzeines A, B, and C, radicamines A and B, 2,5-imino-1,2,5-trideoxy-L-glucitol, -homofuconojirimycin, myrciacitrin IV, dehydrotrametenolic acid, corosolic acid (Glucosol™), 4-(α-rhamnopyranosyl)ellagic acid, and 1,2,3,4,6- pentagalloylglucose have shown significant antidiabetic activities. Among active medicinal herbs, Momordica charantia L. (Cucurbitaceae), Pterocarpus marsupium Roxb. (Leguminoceae), and Trigonella foenum graecum L. (Leguminosae) have been reported as beneficial for treatment of type 2 diabetes.

Preventative Effects of Rosiglitazone on Restenosis After Coronary Stent Implantation in Patients With Type 2 Diabetes Donghoon Choi , MD, PHD 1 , Soo-Kyung Kim , MD 2 3 , Sung-Hee Choi , MD 1 , Young-Guk Ko , MD 1 , Chul-Woo Ahn , MD, PHD 1 2 , Yangsoo Jang , MD, PHD 1 2 , Sung-Kil Lim , MD, PHD 1 2 , Hyun-Chul Lee , MD, PHD 1 2 and Bong-Soo Cha , MD, PHD 1 2 1 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea 2 Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea 3 Department of Internal Medicine, College of Medicine, Pochon CHA University, Sungnam, Kyonggi-do, Korea Address correspondence and reprint requests to Prof. Bong-Soo Cha, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-749, Korea. E-mail: bscha{at}yumc.yonsei.ac.kr Abstract OBJECTIVE —Despite the popularity of coronary stenting in coronary artery disease (CAD), restenosis remains a challenging clinical problem. This study evaluated the efficacy of rosiglitazone for preventing in-stent restenosis in type 2 diabetic patients. RESEARCH DESIGN AND METHODS —We conducted a prospective, randomized, case-controlled trial involving 95 diabetic patients with CAD who were randomly assigned to either the control or rosiglitazone group (48 and 47 patients, respectively). Quantitative coronary angiography (QCA) was performed at study entry and again at 6-month follow-up. The primary end point was the restenosis rate, which was determined by QCA. RESULTS —Eighty-three patients (45 patients with 55 lesions in the control group and 38 patients with 51 lesions in the rosiglitazone group) completed follow-up angiography. Rosiglitazone treatment for 6 months reduced fasting insulin concentration. The high-sensitivity C-reactive protein concentration was significantly reduced in the rosiglitazone group compared with that in the control group (from 2.92 ± 1.98 to 0.62 ± 0.44 mg/l, P < 0.001 vs. from 2.01 ± 1.33 to 1.79 ± 1.22 mg/l, P = NS). However, the baseline and follow-up glucose and lipid concentrations were not different between two groups. The rate of in-stent restenosis was significantly reduced in the rosiglitazone group compared with the control group (for stent lesions: 17.6 vs. 38.2%, P = 0.030). The rosiglitazone group had a significantly lower degree of diameter stenosis (23.0 ± 23.4% vs. 40.9 ± 31.9%, P = 0.004) compared with the control group. CONCLUSIONS —We demonstrated that treatment with rosiglitazone significantly reduces in-stent restenosis in diabetic patients with CAD who underwent coronary stent implantation. CAD, coronary artery disease hsCRP, high-sensitivity C-reactive protein MLD, minimal lumen diameter PPAR, peroxisome proliferator–activated receptor QCA, quantitative coronary angiography TZD, thiazolidinedione VSMC, vascular smooth muscle cell Footnotes D.C. and S.-K.K. contributed equally to this work. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. See accompanying editorial, p. 2764. Accepted August 4, 2004. Received June 2, 2004. DIABETES CARE

Remote ischemic preconditioning (RIPC) induces transient episodes of ischemia by the occlusion of blood flow in non-target tissue, before a subsequent ischemia-reperfusion injury. When RIPC is applied before percutaneous coronary intervention (PCI), the kidneys may be protected against ischemia-reperfusion injury and subsequently contrast-induced acute kidney injury (CI-AKI). The aim of this study was to evaluate the efficacy of RIPC for the prevention of CI-AKI in patients with diabetes with pre-existing chronic kidney disease (CKD) undergoing elective PCI. This randomized, double-blind, sham-controlled study enrolled patients with diabetes scheduled for elective PCI with eGFR ≤60 ml/min/1.73 m2 or urinary albumin creatinine ratio of >300 mg/g to receive either RIPC or the sham ischemic preconditioning. One hundred and two patients (68.9 ± 8.2 years old, 47.1% men) were included. Baseline eGFR, creatinine and serum NGAL was similar between RIPC and control groups (48.5 ± 12 ml/min vs. 46.6 ± 10 ml/min, p = 0.391; 1.42 ± 0.58 mg/dl vs. 1.41 ± 0.34 mg/dl, p = 0.924; and 136.0 ± 45.0 ng/ml vs. 137.6 ± 43.3 ng/ml, p = 0.961, respectively). CI-AKI occurred in 13.7% (14/102) of the total subjects, with both RIPC and control groups having an equal incidence of 13.7% (7/51). No significant differences were seen in creatinine, NGAL, cardiac enzymes (troponin T, CKMB) and hs-CRP between the groups post-procedure. In this study, RIPC applied prior to elective PCI was not effective in preventing CI-AKI in patients with diabetes with pre-existing CKD. ClinicalTrials.gov NCT02329444.

Dentin hypersensitivity is characterized by transient, sharp pain resulting from dentin exposure due to enamel or cementum loss. Current treatments, which primarily focus on superficial tubule occlusion or nerve desensitization, provide only temporary relief. Copine7 (CPNE7) induces odontoblast differentiation and physiologic dentin regeneration, enabling biological dentin sealing and presenting a novel therapeutic approach. This study reports the first‐in‐human results of a randomized, double‐blind, dose‐escalation phase 1/2a clinical trial evaluating the safety, tolerability, preliminary efficacy, and pharmacokinetics of the CPNE7‐derived functional peptide (selcopintide) in patients with dentin hypersensitivity. In Part A (Single Ascending Dose, SAD), 24 participants received a single topical application of selcopintide at ascending doses (2.5, 5, and 10 μg/tooth) in a 6:2 randomization ratio (treatment: placebo). In Part B (Multiple Ascending Dose, MAD), 16 participants received three topical applications (5 and 10 μg/tooth) over 15 days (day 1, 8, and 15; visits 2–4) with the same randomization ratio. Efficacy endpoints were assessed by changes in cold water, evaporative air, and tactile sensitivity. In Part B, the 10 μg selcopintide group demonstrated statistically significant reductions from the baseline across all three measures (p < 0.05), with a mean decrease of −23.2 ± 19.4 mm in VAS, the primary efficacy endpoint. All doses were well tolerated, with no serious adverse events and no detectable systemic absorption of selcopintide. These findings support the safety, tolerability, and preliminary efficacy of selcopintide as a novel therapeutic candidate for the treatment of dentin hypersensitivity.

The supracondylar process is a beak-shaped bony process on the anteromedial aspect of the distal humerus. The ligament of Struthers is a fibrous band extending from the tip of the process to the medial epicondyle. The median nerve and brachial artery pass under the ligament of Struthers and consequently can be compressed, causing supracondylar process syndrome. As a rare cause of proximal median nerve entrapment, supracondylar process syndrome is triggered when the median nerve is located in the superficial or deep layer of the ligament of Struthers as a result of anatomical variation. The supracondylar process can be easily detected on X-ray images obtained in oblique views but may not be identified in only anteroposterior or lateral views. In this article, we present 2 cases of supracondylar process syndrome and describe the process of diagnosis and treatment and results of a literature review.

Skin cancer should be excised with sufficient margin to reduce recurrence rate. However, the surgeon always has to worry about the reconstruction method of skin defects after excision. In particular, defects in the plantar surface of the foot are difficult to reconstruct due to their position and structure, and various methods are applied by each surgeon. Surgeons think which methods are easier to apply to patients and less morbidity. To alleviate these concerns, we applied artificial dermal substitute to skin defects after skin cancer. Bowen's disease (squamous cell carcinoma in situ) and melanoma in situ on the plantar surface of the foot were subjected to wide excision with sufficient margin. After excision, a skin defect with exposed plantar fascia was applied with a matrix defect and vacuum. A granulation tissue (dermal matrix) was formed and a split-thickness skin graft was performed. Both patients had good functional results and no problems with skin donor sites. Thus, we report a skin graft method that is relatively easy to apply after skin cancer excision on the plantar surface of the foot.

A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy 1 . However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells 2 , 3 , 4 , 5 , 6 . Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells 7 . We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

We describe methods for generating artificial transcription factors capable of up- or downregulating the expression of genes whose promoter regions contain the target DNA sequences. To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors.