• Communications for Statistical Applications and Methods
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• 제30권1호
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• pp.1-19
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• 2023

Observational data with missing or incomplete data are common in biomedical research. Multiple imputation is an effective approach to handle missing data with the ability to decrease bias while increasing statistical power and efficiency. In recent years propensity score (PS) matching has been increasingly used in observational studies to estimate treatment effect as it can reduce confounding due to measured baseline covariates. In this paper, we describe in detail approaches to competing risk analysis in the setting of incomplete observational data when using PS matching. First, we used multiple imputation to impute several missing variables simultaneously, then conducted propensity-score matching to match statin-exposed patients with those unexposed. Afterwards, we assessed the effect of statin exposure on the risk of heart failure-related hospitalizations or emergency visits by estimating both relative and absolute effects. Collectively, we provided a general methodological framework to assess treatment effect in incomplete observational data. In addition, we presented a practical approach to produce overall cumulative incidence function (CIF) based on estimates from multiple imputed and PS-matched samples.

• Biomolecules & Therapeutics
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• 제25권1호
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• pp.80-90
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• 2017

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, $S1P_{1-5}$. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn's disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications.

• 동의생리병리학회지
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• 제18권2호
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• pp.381-388
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• 2004

After the author of 'Luxinjing' explained the children's characters using the concept of Pure-Yang, the term has been widely exploited in the literature of Oriental pediatrics, Its meaning could be summed up in three general categories, namely: Shengyang(盛陽), Zhiyinzhiyang(稚陰稚陽) and Shaoyang(少陽). The implications of Pure-Yang were different in each dynasties of China. By the early Qing(淸) period, it meant mostly Shengyang(盛陽), but its meaning moved in the direction of Zhiyinzhiyang(稚陰稚陽) after Wu Jutong(吳鞠通). And this movement in the interpretation of this term was largely triggered by the pharmaceutical concerns of doctors as too much medicine of cooling and gastrointestinal effect was used to 'cool off' the over-charged Yang characters(盛陽) of children, causing considerable detrimental side effects to the children's body. The concept of Zhiyinzhiyang(稚陰稚陽) which emphasizes the fragility of children's body thus came in action. The meaning of physiological terms in Oriental Medicine is essentially linked to its clinical applications as we have seen in the case of Pure Yang. In that respect, the recent interpretation of Pure-Yang as Shaoyang(少陽) among physicians in China seems lacking in its crucial counterpart, which is its clinical applications. No theory can prove fruitful in the absence of its practice.

• Asian-Australasian Journal of Animal Sciences
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• 제33권2호
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• pp.360-372
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• 2020

Objective: Specific genomic sites can be recognized and permanently modified by genome editing. The discovery of endonucleases has advanced genome editing in pigs, attenuating xenograft rejection and cross-species disease transmission. However, off-target mutagenesis caused by these nucleases is a major barrier to putative clinical applications. Furthermore, off-target mutagenesis by genome editing has not yet been addressed in pigs. Methods: Here, we generated genetically inheritable α-1,3-galactosyltransferase (GGTA1) knockout Yucatan miniature pigs by combining transcription activator-like effector nuclease (TALEN) and nuclear transfer. For precise estimation of genomic mutations induced by TALEN in GGTA1 knockout pigs, we obtained the whole-genome sequence of the donor cells for use as an internal control genome. Results: In-depth whole-genome sequencing analysis demonstrated that TALEN-mediated GGTA1 knockout pigs had a comparable mutation rate to homologous recombination-treated pigs and wild-type strain controls. RNA sequencing analysis associated with genomic mutations revealed that TALEN-induced off-target mutations had no discernable effect on RNA transcript abundance. Conclusion: Therefore, TALEN appears to be a precise and safe tool for generating genomeedited pigs, and the TALEN-mediated GGTA1 knockout Yucatan miniature pigs produced in this study can serve as a safe and effective organ and tissue resource for clinical applications.

• 수면정신생리
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• 제1권1호
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• pp.36-46
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• 1994

The event-related potentials are difined as the changes in voltage that occur at paticular time before, during and after something that happens in the physical world or some psychological processes. The possibilities of clinical applications of ERP are considered because the endogenous potentials such as P3 and contingent negative variation(CNV) are determined by the psychological significance of the stimulus. The P3 is a positive wave that occurs when a subject detects an informative task-relevant stimulus. The P3 amplitude and latency are affected by the various factors as subjective probabilites, stimulus meaning and information transmission. It is suggested that P3 wave is associated with the decision making, cognitive or perceptual closure, memory updating and transfer of information to consciousness etc. Although the intracerebral origin of the P3 wave is not known, the P3 may have multiple intracerebral generators. The CNV is a slow potential shift occuring during the foreperiod, between warning and response signals, in a reaction time experiment. It is related to expectancy, preparation etc. The abnormal findings of P3 wave and CNV in various psychiatric disorders are also discussed.

• Advances in Traditional Medicine
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• 제9권1호
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• pp.1-13
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• 2009

Medicinal herbs are significant source of synthetic and herbal drugs. In the commercial market, medicinal herbs are used as raw drugs, extracts or tinctures. Isolated active constituents are used for applied research. For the last few decades, phytochemistry (study of plants) has been making rapid progress and herbal products are becoming popular. According to Ayurveda, the ancient healing system of India, the classical texts of Ayurveda, Charaka Samhita and Sushruta Samhita were written around 1000 B.C. The Ayurvedic Materia Medica includes 600 medicinal plants along with therapeutics. Herbs like turmeric, fenugreek, ginger, garlic and holy basil are integral part of Ayurvedic formulations. The formulations incorporate single herb or more than two herbs (poly-herbal formulations). Medicinal herb contains multitude of chemical compounds like alkaloids, glycosides, saponins, resins, oleoresins, sesquiterpene, lactones and oils (essential and fixed). Today there is growing interest in chemical composition of plant based medicines. Several bioactive constituents have been isolated and studied for pharmacological activity. R. cordifolia is an important medicinal plant commonly used in the traditional and Ayurvedic system of medicine for treatment of different ailments. This review illustrates its major constituents, pharmacological actions substantiating the claims made about this plant in the traditional system of medicine and its clinical applications.

• Toxicological Research
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• 제26권1호
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• pp.1-8
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• 2010

The process of new drug development consists of several stages; after identifying potential candidate compounds, preclinical studies using animal models link the laboratory and human clinical trials. Among many steps in preclinical studies, toxicology and safety assessments contribute to identify potential adverse events and provide rationale for setting the initial doses in clinical trials. Gene modulation is one of the important tools of modern biology, and is commonly employed to examine the function of genes of interest. Advances in new drug development have been achieved by exploding information on target selection and validation using genetically modified animal models as well as those of cells. In this review, a recent trend of genetically modified methods is discussed with reference to safety assessments, and the exemplary applications of gene-modulating tools to the tests in new drug development were summarized.

• BMB Reports
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• 제37권5호
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• pp.546-551
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• 2004

The increasing pace of development in molecular biology during the last decade has had a direct effect on mass testing and diagnostic applications, including blood screening. We report the model Microarray that has been developed for Hepatitis B virus (HBV) and Hepatitis D virus (HDV) detection. The specific primer pairs of PCR were designed using the Primer Premier 5.00 program according to the conserved regions of HBV and HDV. PCR fragments were purified and cloned into pMD18-T vectors. The recombinant plasmids were extracted from positive clones and the target gene fragments were sequenced. The DNA microarray was prepared by robotically spotting PCR products onto the surface of glass slides. Sequences were aligned, and the results obtained showed that the products of PCR amplification were the required specific gene fragments of HBV, and HDV. Samples were labeled by Restriction Display PCR (RD-PCR). Gene chip hybridizing signals showed that the specificity and sensitivity required for HBV and HDV detection were satisfied. Using PCR amplified products to construct gene chips for the simultaneous clinical diagnosis of HBV and HDV resulted in a quick, simple, and effective method. We conclude that the DNA microarray assay system might be useful as a diagnostic technique in the clinical laboratory. Further applications of RD-PCR for the sample labeling could speed up microarray multi-virus detection.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1713-1718
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• 2012

Advanced imaging approaches (computed tomography, CT; magnetic resonance imaging, MRI; $^{18}F$-fluorodeoxyglucose positron emission tomography, FDG PET) have increased roles in cervical cancer staging and management. The recent FIGO (International Federation of Gynecology and Obstetrics) recommendations encouraged applications to assess the clinical extension of tumors rather than relying on clinical examinations and traditional non-cross sectional investigations. MRI appears to be better than CT for primary tumors and adjacent soft tissue involvement in the pelvis. FDG-PET/CT has increased in usage with a particular benefit for whole body evaluation of tumor metabolic activity. The potential benefits of advanced imaging are assisting selection of treatment based upon actual disease extent, to adequately treat a tumor with minimal normal tissue complications, and to predict the treatment outcomes. Furthermore, sophisticated external radiation treatment and brachytherapy absolutely require advanced imaging for target localization and radiation dose calculation.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제34권2호
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• pp.155-161
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• 2012

Platelet-rich fibrin (PRF) is a strong but flexible fibrin including a enrich platelet which contain growth factors and cytokines. PRF can be made very simply and requires no artificial additives unlike platelet-rich plasma. While PRF is remodeled and released in the tissue, this induces cell growth, vascularization, collagen synthesis, osteoblast differentiation and an anti-inflammatory reaction. Taking advantage of these functions, PRF can stimulate regeneration of bone and soft tissue in a diverse number of ways during the course of hemostasis, wound coverage, preservation, and reconstruction of alveolar bone. Moreover, the use of PRF to improve bone regeneration has become a recent technique in implantology. In this study, through a literature review of PRF's existing clinical applications, we classified a range of potential PRF oral and maxillofacial surgery applications including preservation of extraction sockets, guided bone graft, sinus lift, dressing and periodontal treatment. This trial gave us chance to confirm the usefulness of PRF. Recently, updated clinical studies results concerning skin and tendon wound healing have become available. These results suggest that the usage of RPF will gradually expand.