The diameter of the world wide web

Despite its increasing role in communication, the world wide web remains the least controlled medium: any individual or institution can create websites with unrestricted number of documents and links. While great efforts are made to map and characterize the Internet's infrastructure, little is known about the topology of the web. Here we take a first step to fill this gap: we use local connectivity measurements to construct a topological model of the world wide web, allowing us to explore and characterize its large scale properties.Comment: 5 pages, 1 figure, updated with most recent results on the size of the ww

Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion

Objective: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. Methods: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. Results: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. Conclusion: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development

Low-Dose 3D Rotational Angiography in Measuring the Size of Intracranial Aneurysm: In Vitro Feasibility Study Using Aneurysm Phantom

Purpose Three-dimensional (3D) measurement of intracranial aneurysms is important in planning endovascular treatment, and 3D rotational angiography (RA) is effective in accurate measurement. The purpose of this study was to evaluate the feasibility of low dose 3D RA (5 seconds 0.10 μGy/frame) in measuring an intracranial aneurysm using an in vitro phantom. Materials and Methods We investigated an in vitro 3D phantom of an intracranial aneurysm with 10 acquisitions of 3D RA with a conventional dose (5 seconds 0.36 μGy/frame) and 10 acquisitions with a low-dose (5 seconds 0.10 μGy/frame). 3D size and neck diameters of the aneurysm were measured and compared between the 2 groups (conventional and low-dose) using noninferiority statistics. Results The aneurysm measurements were well-correlated between the 2 readers, and noninferiority in the measurement of aneurysmal size of low-dose 3D RA was demonstrated, as the upper margin of the 1-sided 97.5% confidence interval did not cross the pre-defined noninferiority margin of 0.2 mm by the 2 readers. Conclusion Low-dose (5 seconds 0.10 μGy/frame) cerebral 3D RA is technically feasible and not inferior in in vitro 3D measurement of an intracranial aneurysm. Thus, low-dose 3D RA is promising and needs further evaluation for its clinical utility in the planning of endovascular treatment of an intracranial aneurysm

The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort

Background As the need for a nationwide organ-transplant registry emerged, a prospective registry, the Korean Organ Transplantation Registry (KOTRY), was initiated in 2014. Here, we present baseline characteristics and outcomes of the kidney-transplant cohort for 2014 through 2019. Methods The KOTRY consists of five organ-transplant cohorts (kidney, liver, lung, heart, and pancreas). Data and samples were prospectively collected from transplant recipients and donors at baseline and follow-up visits; and epidemiological trends, allograft outcomes, and patient outcomes, such as posttransplant complications, comorbidities, and mortality, were analyzed. Results From 2014 to 2019, there were a total of 6,129 registered kidney transplants (64.8% with living donors and 35.2% with deceased donors) with a mean recipient age of 49.4 ± 11.5 years, and 59.7% were male. ABO-incompatible transplants totaled 17.4% of all transplants, and 15.0% of transplants were preemptive. The overall 1- and 5-year patient survival rates were 98.4% and 95.8%, respectively, and the 1- and 5-year graft survival rates were 97.1% and 90.5%, respectively. During a mean follow-up of 3.8 years, biopsy-proven acute rejection episodes occurred in 17.0% of cases. The mean age of donors was 47.3 ± 12.9 years, and 52.6% were male. Among living donors, the largest category of donors was spouses, while, among deceased donors, 31.2% were expanded-criteria donors. The mean serum creatinine concentrations of living donors were 0.78 ± 0.62 mg/dL and 1.09 ± 0.24 mg/dL at baseline and 1 year after kidney transplantation, respectively. Conclusion The KOTRY, a systematic Korean transplant cohort, can serve as a valuable epidemiological database of Korean kidney transplants

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis

Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication

Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

Background/AimsSpontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection.MethodsNinety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels.ResultsOnly one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥5.1×107 IU/mL and ALT ≥5×ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure.ConclusionsSpontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection

Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial

Backgrounds: Alzheimer's disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. Objectives: We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer's disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood-derived MSCs (hUCB-MSCs). Methods: We recruited nine mild-to-moderate Alzheimer's disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107 cells/2 mL), and six patients received a high dose (3.0 × 107 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. Results: After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. Conclusions: Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy