• Title/Summary/Keyword: Trial Functions

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An R package UnifiedDoseFinding for continuous and ordinal outcomes in Phase I dose-finding trials

  • Pan, Haitao;Mu, Rongji;Hsu, Chia-Wei;Zhou, Shouhao
    • Communications for Statistical Applications and Methods
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    • v.29 no.4
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    • pp.421-439
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    • 2022
  • Phase I dose-finding trials are essential in drug development. By finding the maximum tolerated dose (MTD) of a new drug or treatment, a Phase I trial establishes the recommended doses for later-phase testing. The primary toxicity endpoint of interest is often a binary variable, which describes an event of a patient who experiences dose-limiting toxicity. However, there is a growing interest in dose-finding studies regarding non-binary outcomes, defined by either the weighted sum of rates of various toxicity grades or a continuous outcome. Although several novel methods have been proposed in the literature, accessible software is still lacking to implement these methods. This study introduces a newly developed R package, UnifiedDoseFinding, which implements three phase I dose-finding methods with non-binary outcomes (Quasi- and Robust Quasi-CRM designs by Yuan et al. (2007) and Pan et al. (2014), gBOIN design by Mu et al. (2019), and by a method by Ivanova and Kim (2009)). For each of the methods, UnifiedDoseFinding provides corresponding functions that begin with next that determines the dose for the next cohort of patients, select, which selects the MTD defined by the non-binary toxicity endpoint when the trial is completed, and get oc, which obtains the operating characteristics. Three real examples are provided to help practitioners use these methods. The R package UnifiedDoseFinding, which is accessible in R CRAN, provides a user-friendly tool to facilitate the implementation of innovative dose-finding studies with nonbinary outcomes.

Probiotic supplementation has sex-dependent effects on immune responses in association with the gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial

  • Chong-Su Kim;Min Ho Jung;Eun Young Choi;Dong-Mi Shin
    • Nutrition Research and Practice
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    • v.17 no.5
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    • pp.883-898
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    • 2023
  • BACKGROUND/OBJECTIVES: Probiotics have been suggested as potent modulators of age-related disorders in immunological functions, yet little is known about sex-dependent effects of probiotic supplements. Therefore, we aimed to investigate sex-dependent effects of probiotics on profiles of the gut microbiota and peripheral immune cells in healthy older adults. SUBJECTS/METHODS: In a randomized, double-blind, placebo-controlled, multicenter trial, healthy elderly individuals ≥ 65 yrs old were administered probiotic capsules (or placebo) for 12 wk. Gut microbiota was analyzed using 16S rRNA gene sequencing and bioinformatic analyses. Peripheral immune cells were profiled using flow cytometry for lymphocytes (natural killer, B, CD4+ T, and CD8+ T cells), dendritic cells, monocytes, and their subpopulations. RESULTS: Compared with placebo, phylum Firmicutes was significantly reduced in the probiotic group in women, but not in men. At the genus level, sex-specific responses included reductions in the relative abundances of pro-inflammatory gut microbes, including Catabacter and unclassified_Coriobacteriales, and Burkholderia and unclassified Enterobacteriaceae, in men and women, respectively. Peripheral immune cell profiling analysis revealed that in men, probiotics significantly reduced the proportions of dendritic cells and CD14+ CD16- monocytes; however, these effects were not observed in women. In contrast, the proportion of total CD4+ T cells was significantly reduced in women in the probiotic group. Additionally, serum lipopolysaccharide-binding protein levels showed a decreasing tendency that were positively associated with changes in gut bacteria, including Catabacter (ρ = 0.678, P < 0.05) and Burkholderia (ρ = 0.673, P < 0.05) in men and women, respectively. CONCLUSIONS: These results suggest that probiotic supplementation may reduce the incidence of inflammation-related diseases by regulating the profiles of the gut microbiota and peripheral immune cells in healthy elders in a sex-specific manner.

Effect of Gaze Stabilization Exercise with Balance Exercise on Static and Dynamic Balance Function of Healthy Young A dults: A Randomized Controlled Trial

  • Yi Wu;Xing- HAN Zhou;Yongbum Jung;Myoung-Kwon Kim
    • Journal of the Korean Society of Physical Medicine
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    • v.19 no.2
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    • pp.1-16
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    • 2024
  • PURPOSE: This study examined the effects of four weeks of gaze stabilization exercises and balance training on the static and dynamic balance functions. METHODS: The study was an assessor-blinded randomized controlled trial conducted at Daegu University in South Korea. Thirty subjects who fulfilled the inclusion criteria were selected and divided randomly into three groups containing ten each. The first group received balance exercises with gaze stabilizing exercises (BGG). The second group received a balance exercise (BEG), and the third group received gaze-stabilizing exercise (GEG). Each group exercised for 40 minutes, three times a week for four weeks. The subjects were asked to complete the following static balance test: 1) one-leg standing test, 2) sharpened Romberg test, dynamic balance test, 3) Y-balance test, and 4) single-leg stand-squat-stand test. The static and dynamic balance were measured before and after four weeks to determine the effect of exercise on balance. RESULTS: The static (OLS and SRT) and dynamic (YBT and SST) balance tests showed significant differences in the surface and length of the three groups (p < .05), and the y-balance score effect size, 11.477 (p < .05), was improved significantly. On the other hand, the change in BGG value was larger than those of BEG and GEG, and the improvements in balance control were the most significant. CONCLUSION: After four weeks of exercise, BGG showed the best improvement in static and dynamic balance, suggesting that this specific type of gaze stabilization exercise with balance exercise may benefit healthy young adults.

Safety Test of Brown Rice Expressing Arabidopsis Calcium Transporter by Feeding Trial in Mice (애기장대 칼슘수송체를 발현하는 형질전환 현미의 생쥐 식이를 통한 안전성 평가)

  • Kim, Kyung-Min;Kim, Chang-Kil;Kim, Byung-Oh
    • Journal of Life Science
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    • v.18 no.10
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    • pp.1390-1394
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    • 2008
  • Previously, we found that the transgenic rice plants over-expressing the Arabidopsis $H^+/Ca^{2+}$ antiporter CAX 1 (accession no. U57411) gene accumulated 2.7 to 7.5-fold more calcium in the T3 rice grains as compared to those of control. To examine physiological safety of the $T_3$ rice grains, the effect of the $T_3$ brown rice on change in levels of body weight and white blood cells was compared with that of the control Ilpum brown rice by feeding trial in mice. During the feeding trial for one month, there was no significant difference between two mice groups, which were fed by the $T_3$ brown rice or Ilpum brown rice. There were no detectable differences in their effects on immune functions including plaque-forming unit, peritoneal macrophage number, and NK-cell activity. In addition, biochemical analysis of the blood failed to exhibit any difference between two mice groups. Together, these results suggested that the $T_3$ brown rice, which was produced from a genetically modified organism (GMO), might be safe and possess a potential to be applicable as calcium-fortified feed or food. Long-term safety of the $T_3$ brown rice, however, remains to be elucidated.

Ginsenoside Re Inhibits Osteoclast Differentiation in Mouse Bone Marrow-Derived Macrophages and Zebrafish Scale Model

  • Park, Chan-Mi;Kim, Hye-Min;Kim, Dong Hyun;Han, Ho-Jin;Noh, Haneul;Jang, Jae-Hyuk;Park, Soo-Hyun;Chae, Han-Jung;Chae, Soo-Wan;Ryu, Eun Kyoung;Lee, Sangku;Liu, Kangdong;Liu, Haidan;Ahn, Jong-Seog;Kim, Young Ock;Kim, Bo-Yeon;Soung, Nak-Kyun
    • Molecules and Cells
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    • v.39 no.12
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    • pp.855-861
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    • 2016
  • Ginsenosides, which are the active materials of ginseng, have biological functions that include anti-osteoporotic effects. Aqueous ginseng extract inhibits osteoclast differentiation induced by receptor activator of NF-${\kappa}B$ ligand (RANKL). Aqueous ginseng extract produces chromatography peaks characteristic of ginsenosides. Among these peaks, ginsenoside Re is a major component. However, the preventive effects of ginsenoside Re against osteoclast differentiation are not known. We studied the effect of ginsenoside Re on osteoclast differentiation, RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, and formation of multinucleated osteoclasts in vitro. Ginsenoside Re hampered osteoclast differentiation in a dose-dependent manner. In an in vivo zebrafish model, aqueous ginseng extract and ginsenoside Re had anti-osteoclastogenesis effects. These findings suggest that both aqueous ginseng extract and ginsenoside Re prevent bone resorption by inhibiting osteoclast differentiation. Ginsenoside Re could be important for promoting bone health.

The Effect of Ankle Kinesio Taping on Postural Control Functions in University Students: a randomized control trial (발목관절의 키네지오 테이핑 적용이 대학생들의 운동 수행 시 자세조절기능에 미치는 영향)

  • Eom, Se-Young;Lee, Won-Jun;Lee, Jae-Il;Lee, Eun-Hee;Lee, Hye-Young;Chung, Eun-Jung
    • Journal of Korean Physical Therapy Science
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    • v.25 no.1
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    • pp.11-19
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    • 2018
  • Purpose : The purpose of this study was to examine the effects of ankle kinesio taping on postural control function during exercise in university students. Method : Thirty subjects were randomly allocated to three groups: Y taping group (n=20), I taping group (n=20) and Non-taping group (n=20). All groups underwent the same exercise program including stretching for 30 minutes. The exercise program proceeded in the following order: five minutes of stretching, a 20-minutes exercise program, and additional five 5 minutes of stretching. Of the eight exercise methods suggested by Purcell et al, seven were chosen (lateral shuffle, forward & backward running, agility ladder, figure-of-8, forward jogging while jumping over cones, wall jumps and zigzags); $90^{\circ}$ cuts with lateral shuffle were omitted. The postural control functions was measured participants's perceptions of stability, confidence, and reassurance using methods suggested by Purcell et al,. Result : The confidence was significant difference in I taping group compared to Non taping group. The reassurance was significant difference in Y taping group and I taping group compared to Non taping group. Conclusion : The Kinesio taping increased confidence, and reassurance during exercise in university students. Additional research on Kinesio taping for improving range of motion and agility is need.

The Effect of Insole Height on Lumbosacral Angle and Body Function in Male University Students

  • Lee, Young Sin;Yu, Seong Hun;Kim, Seong Su
    • Journal of the Ergonomics Society of Korea
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    • v.34 no.4
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    • pp.303-312
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    • 2015
  • Objective: The aim of this study is to investigate the effect of insole height change in the lumbosacral angle and physical functions in healthy males. Background: In order to release male's dissatisfaction with his height and to increase satisfaction with his body, using insole is generalized. There have been researches on female's body change in accordance with function of insole and heel height, whereas there are few researches on males. Method: Participants were divided into three groups. A control group had 10 participants who wore 0cm insole. Experimental group I had 10 participants who wore 2cm insole. Experimental group II had 10 participants who wore 4cm insole. All participants wore insoles during their daily lives for a trial period of 8 weeks. The results were evaluated before and after comparison, and we measured lumbosacral angle, balance (dynamic balance, agility, quickness) and lumbar pain (LBP). Results: This study showed that insole height affected lumbosacral angle and dynamic balance and pain. In particular, there were significant differences in the 4cm group among the three groups (p<.05). The 2cm group did show a significant difference in lumbosacral angle and pain (p<.05). Furthermore, no significant difference was observed within the control group. Conclusion: The 4cm insole height suggests that the increase of lumbosacral angle contributes to some changes in LBP, balance, pain and physical functions, probably leading to negative effects on variety of activities of daily life. Application: The results of wearing insoles with proper height will help to prevent musculoskeletal disorders.

Kupffer Cells Suppress Hepatocarcinogenesis and Metastasis in Tumor Orthotopic Implanted Kunming Mice

  • Li, X.Y.;Wang, M.Y.;Zhang, J.Y.;Li, J.Z.;Gong, J.P.;Zhang, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6393-6398
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    • 2013
  • In this research, we used $GdCl_3$ (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25% $GdCl_3$ solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-${\alpha}$ and IFN-${\gamma}$ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The $GdCl_3$ pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-${\alpha}$ and IFN-${\gamma}$ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened.

A Simple and Rapid Method for Functional Analysis of Plant Growth-promoting Rhizobacteria Using the Development of Cucumber Adventitious Root System

  • Bae, Yeoung-Seuk;Park, Kyung-Seok;Lee, Young-Gee;Choi, Ok-Hee
    • The Plant Pathology Journal
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    • v.23 no.3
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    • pp.223-225
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    • 2007
  • Many plant growth-promoting rhizobacteria (PGPRs) have been known for beneficial effects on plants including biological control of soilborne pathogens, induced systemic resistance to plant pathogens, phytohormone production, and improvement of nutrient and water uptake of plants. We developed a simple and rapid method for screening potential PGPR, especially phytohormone producing rhizobacteria, or for analyzing their functions in plant growth using cucumber seedling cuttings. Surface-sterilized cucumber seeds were grown in a plastic pot containing steamed vermiculite. After 7 days of cultivation, the upper part 2 cm in length of cucumber seedling, was cut and used as cucumber cuttings. The base of cutting stem was then dipped in a microcentrifuge tube containing 1.5ml of a bacterial suspension and incubated at $25^{\circ}C$ with a fluorescent light for 10 days. Number and length of developed adventitious roots from cucumber cuttings were examined. The seedling cuttings showed various responses to the isolates tested. Some isolates resulted in withering at the day of examination or in reduced number of roots developed. Several isolates stimulated initial development of adventitious roots showing more adventitious root hair number than that of untreated cuttings, while some isolate had more adventitious root hair number and longer adventitious roots than that of untreated control. Similar results were obtained from the trial with rose cuttings. Our results suggest that this bioassay method may provide a useful way for differentiating PGPR's functions involved in the development of root system.

Effects of Water-extract Mixture of Scutellariae baicalensis GEORGI, Acarus gramineus SOLAND and Gastrodia elata BLUME on Cultured Rat Cortical Neurons and Enhancement of Learning and Memory Power (황금(黃芩), 석창포(石菖蒲), 천마(天麻) 물추출액 혼합물이 배양한 흰쥐 대뇌신경세포의 활성과 학습능력 증진 효능)

  • Bae, Chul-Hwan;Jung, Hyun-Jung;Jung, Seung-Hyun;Moon, Il-Soo;Lee, Won-Chul;Sin, Gil-Jo
    • Journal of Life Science
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    • v.19 no.6
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    • pp.756-764
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    • 2009
  • Scutellariae baicalensis GEORGt Acorus gramineus SOLAND and Gastrodia elata BLUME are traditional medicines used in the treatment of incipient stoke. In this study we investigated their effects on various aspects of neuronal differentiation in single or composite forms. Water-extracts of these medicines showed neuroprotective effects on cultured rat cortical neurons in normoxia and hypoxia. To understand the mechanism for neuroprotection we carried out various cell biological assays. They stimulated initial differentiation of neuronal development (transition from stage 1 to 2), and increased the number of spines and the length and number of dendritic processes. These effects were best manifested in the experimental group, which were given a mixture of the three kinds of extracts (p<0.01). To assess improvement of brain functions we carried out Morris water-maze tests for the mice that were fed on these extracts instead of water for 4 weeks. The experimental groups, especially those which were given the mixture of the three kinds of extract, showed significant (p<0.01) enhancement in memory as early as one day after the learning trial. These results indicate that these three kinds of extracts have synergistic effects on neuronal protection and improvement of brain functions.