Management of viral hepatitis in liver transplant recipients

Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC

Controllable deposition of organic metal halide perovskite films with wafer-scale uniformity by single source flash evaporation

Conventional solution-processing techniques such as the spin-coating method have been used successfully to reveal excellent properties of organic-inorganic halide perovskites (OHPs) for optoelectronic devices such as solar cell and light-emitting diode, but it is essential to explore other deposition techniques compatible with large-scale production. Single-source flash evaporation technique, in which a single source of materials of interest is rapidly heated to be deposited in a few seconds, is one of the candidate techniques for large-scale thin film deposition of OHPs. In this work, we investigated the reliability and controllability of the single-source flash evaporation technique for methylammonium lead iodide (MAPbI(3)) perovskite. In-depth statistical analysis was employed to demonstrate that the MAPbI(3) films prepared via the flash evaporation have an ultrasmooth surface and uniform thickness throughout the 4-inch wafer scale. We also show that the thickness and grain size of the MAPbI(3) film can be controlled by adjusting the amount of the source and number of deposition steps. Finally, the excellent large-area uniformity of the physical properties of the deposited thin films can be transferred to the uniformity in the device performance of MAPbI(3) photodetectors prepared by flash evaporation which exhibited the responsivity of 0.2 A/W and detectivity of 3.82x10(11) Jones.

A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma

To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) tests sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.This study was supported by grants from the National Research Foundation (NRF) funded by the Ministry of Science & ICT (No. 2017M3A9A7050614, No. 2020R1C1C1012749, and NRF-2017R1D1A1B06029547) and the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (No. HI22C0147

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Observational Arc-Length Effect on Orbit Determination for Korea Pathfinder Lunar Orbiter in the Earth-Moon Transfer Phase Using a Sequential Estimation

In this study, the observational arc-length effect on orbit determination (OD) for the Korea Pathfinder Lunar Orbiter (KPLO) in the Earth-Moon Transfer phase was investigated. For the OD, we employed a sequential estimation using the extended Kalman filter and a fixed-point smoother. The mission periods, comprised between the perigee maneuvers (PM) and the lunar orbit insertion (LOI) maneuver in a 3.5 phasing loop of the KPLO, was the primary target. The total period was divided into three phases: launch–PM1, PM1–PM3, and PM3–LOI. The Doppler and range data obtained from three tracking stations [included in the deep space network (DSN) and Korea Deep Space Antenna (KDSA)] were utilized for the OD. Six arc-length cases (24 hrs, 48 hrs, 60 hrs, 3 days, 4 days, and 5 days) were considered for the arc-length effect investigation. In order to evaluate the OD accuracy, we analyzed the position uncertainties, the precision of orbit overlaps, and the position differences between true and estimated trajectories. The maximum performance of 3-day OD approach was observed in the case of stable flight dynamics operations and robust navigation capability. This study provides a guideline for the flight dynamics operations of the KPLO in the trans-lunar phase

Pricing Various Types of Power Options under Stochastic Volatility

The exotic options with curved nonlinear payoffs have been traded in financial markets, which offer great flexibility to participants in the market. Among them, power options with the payoff depending on a certain power of the underlying asset price are widely used in markets in order to provide high leverage strategy. In pricing power options, the classical Black–Scholes model which assumes a constant volatility is simple and easy to handle, but it has a limit in reflecting movements of real financial markets. As the alternatives of constant volatility, we focus on the stochastic volatility, finding more exact prices for power options. In this paper, we use the stochastic volatility model introduced by Schöbel and Zhu to drive the closed-form expressions for the prices of various power options including soft strike options. We also show the sensitivity of power option prices under changes in the values of each parameter by calculating the resulting values obtained from the formulas

Big Data and government: Evidence of the role of Big Data for smart cities

Scholars are becoming increasingly interested in whether and how government use of Big Data will affect public policy outcomes. Despite such growing scholarly interests, however, little evidence exists on the role Big Data can play in improving government service. We undertake one of the first quantitative studies revealing the potential utility and limitations of “Big Data-based policymaking” by exploring its recent use by the Seoul Metropolitan Government. In 2013, the government introduced the “Owl Bus”—a late-night bus system—the routes of which were selected based on government analyses of Big Data relating to citizens’ late-night taxi and mobile phone use. The findings suggest that the average number of passengers utilizing the Owl Bus routes was significantly greater than that on other daytime bus routes with comparable characteristics. That said, we also present the potential limitations of evidence-based policymaking in general, especially when politics and equity considerations are factored in