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Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis

  • Pyeong Hwa Kim;Chong Hyun Suh;Ho Sung Kim;Kyung Won Kim;Dong Yeong Kim;Eudocia Q. Lee;Ayal A. Aizer;Jeffrey P. Guenette;Raymond Y. Huang
    • Korean Journal of Radiology
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    • v.22 no.4
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    • pp.584-595
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    • 2021
  • Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion: ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

Vegetation Structure of Urban Forests on Mt. Goehwa, Sejong-Si (세종시 괴화산 도시숲의 식생구조)

  • Hyeon-Hwa Kim;Jeong-Eun Lee;Sung-Yeon Lee;Da-Eun Park;Chung-Weon Yun
    • Journal of Korean Society of Forest Science
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    • v.113 no.1
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    • pp.51-65
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    • 2024
  • Phyto-sociological methods were used in this study to assess the vegetation structure of a forest stand at Mt. Goehwa in Sejong-Si with the aim of providing vegetation information for urban forest utilization and management plans. The actual forest vegetation was classified into two types of community groups (Quercus serrata-Lindera obtusiloba and Coreopsis lanceolata community groups) at the highest hierarchical level. The Q. serrata-L. obtusiloba community group was classified into six units, which included artificial forest and natural forest vegetation. Artificial forests were classified into three communities (Pinus rigida, Castanea crenata, and Robinia pseudoacacia), whereas natural forests were classified into three communities (Quercus variabilis, Quercus acutissimaa, and Pinus densiflora). The Coreopsis lanceolata community group, which exhibited vegetative characteristics of urban forest edge areas, was categorized into four units. The urban forest edges were classified into four communities (Indigofera bungeana, Lespedeza bicolor, Amorpha fruticosa, and Lespedeza cuneata). Accordingly, the vegetation structure of Mt. Goehwa was categorized into 10 vegetation unit systems. An importance value analysis showed the highest importance value for C. crenata at 6.7%, followed by P. rigida at 6.4%, and R. pseudoacacia at 6.3%, indicating that the ecological impact of plantation species can be significant on Mt. Goehwa. A community coefficient of similarity analysis revealed that the artificial and natural forests had similar species compositions; however, both forests differed from the urban forest edge. This variation was further confirmed by Detrended correspondence analysis(DCA), with similar results. Canonical correspondence analysis(CCA) showed that the artificial forest and natural forest community types were positively correlated with altitude, bare rock, and the present species. By contrast, the urban forest edge community types were negatively correlated with these factors.

Transcriptome sequencing reveals non-coding RNAs respond to porcine reproductive and respiratory syndrome virus and Haemophilus parasuis co-infection in Kele piglets

  • Jing Zhang;Chunping Zhao;Min Yao;Jing Qi;Ya Tan;Kaizhi Shi;Jing Wang;Sixuan Zhou;Zhixin Li
    • Journal of Animal Science and Technology
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    • v.66 no.4
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    • pp.663-681
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    • 2024
  • Co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS) has severely restricted the healthy development of pig breeding. Exploring disease resistance of non-coding RNAs in pigs co-infected with PRRSV and HPS is therefore critical to complement and elucidate the molecular mechanisms of disease resistance in Kele piglets and to innovate the use of local pig germplasm resources in China. RNA-seq of lungs from Kele piglets with single-infection of PRRSV or HPS and co-infection of both pathogens was performed. Two hundred and twenty-five differentially expressed long non-coding RNAs (DElncRNAs) and 30 DEmicroRNAs (DEmiRNAs) were identified and characterized in the PRRSV and HPS co-infection (PRRSV-HPS) group. Compared with the single-infection groups, 146 unique DElncRNAs, 17 unique DEmiRNAs, and 206 target differentially expressed genes (DEGs) were identified in the PRRSV-HPS group. The expression patterns of 20 DEmiRNAs and DElncRNAs confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) were consistent with those determined by high-throughput sequencing. In the PRRSV-HPS group, the target DEGs were enriched in eight immune Gene Ontology terms relating to two unique DEmiRNAs and 16 DElncRNAs, and the unique target DEGs participated the host immune response to pathogens infection by affecting 15 immune-related Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Notably, competitive endogenous RNA (ceRNA) networks of different groups were constructed, and the ssc-miR-671-5p miRNA was validated as a potential regulatory factor to regulate DTX4 and AEBP1 genes to achieve innate antiviral effects and inhibit pulmonary fibrosis by dual-luciferase reporter assays. These results provided insight into further study on the molecular mechanisms of resistance to PRRSV and HPS co-infection in Kele piglets.

Antidepressant Effect and Mechanism of Picea mariana Essential Oil on Reserpine-Induced Depression Model Mice

  • Ying Wang;Guofeng Shi;Yixi Zeng;Juting Li;Yongyu Wu;Jiahui Zheng;Anjing Xu;Yanqing Ma;Lanyue Zhang;Hui Li
    • Journal of Microbiology and Biotechnology
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    • v.34 no.9
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    • pp.1778-1788
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    • 2024
  • The disturbance of brain biochemical substances serves as a primary cause and aggravating factor of depression. This study aimed to investigate the principal components of Picea mariana and its effect on reserpine-induced depression mice,w ith its relationship with brain central transmitters and related proteins. The main constituents of P. mariana essential oil (PMEO) were analyzed by GC-MS spectrometry. The quiescent time in the tail suspension test (TST) and forced swim test (FST), along with the weight change of the mice was detected. The number of normal neurons was quantified through Nissl staining. Immunohistochemistry was employed to determine the levels of 5HT-1A and 5HT-2A in the brain. Western blotting was utilized to detect 5HT-2A, CRF and TrkB protein levels. RTqPCR was used to detect the mRNA levels of 5HT-1A, 5HT-2A, TrkB, CRF, and BDNF. The main active ingredients of PMEOs were (-) -bornyl acetate (44.95%), γ-Terpinene (14.17%), and β-Pinene (10.12%). PMEOs effectively improved the retardation and weight loss due to anorexia in depression-like mice. This improvement was associated with an increase in the number of normal neurons. After administering different doses of PMEOs, the levels of 5HT-1A, 5HT-2A, CRF, and TrkB were found to be increased in brain tissue. RT-qPCR revealed that the mRNA levels of CRF, 5HT-1A, and 5HT-2A were generally upregulated, whereas TrkB and BDNF were downregulated. PMEO can effectively alleviate depression induced by reserpine, which may be attributed to its regulation of 5HT-1A, 5HT-2A, CRF and TrkB protein expression, thus reducing brain nerve injury.

Characteristics of Vegetation Structure of Managed Area by Oak Wilt Disease in Bukhansan National Park (북한산국립공원 참나무시들음병 방제지역 식생구조 특성 연구)

  • Han, Bong-Ho;Choi, Jin-Woo;Yeum, Jung-Hun;Lee, Kyong-Jae
    • Korean Journal of Environment and Ecology
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    • v.28 no.3
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    • pp.342-356
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    • 2014
  • This study aims to provide the fundamental data for restoration through the analysis of vegetation structure characteristic for managed area with deforest and fumigation among the places damaged by oak wilt disease in Bukhansan National Park. Study areas were selected in six damaged areas with 18 plots ($20m{\times}20m$) including comparing plots between year 2006 and year 2011 after preliminary study finding the exact location with easy access. Analysis items are density and coverage of under story layer, Importance Percentage of under story layer and Importance Percentage of urban adapted species and alien species. As a result, density and coverage under the canopy layer's vegetation was higher than comparing plot in Musugol valley and Soquicheon valley which 4 years and more passed. And Wondobong, Darakwon, Doseonsa and Dobong valley which had not been passed 3 years after deforestation and fumigation decreased in those of vegetation. However, the plots in Wondobong and Doseonsa was analyzed to be higher in density of shrubs than comparing plot. In terms of distirbution of species in under canopy layer which is grown as a upper vegetation, Quercus serrata and Sorbus alnifolia dominated each other in under canopy layer except for Wondobong and Darakwon. Wondobong continuously maintained Quercus mongolica and Q. mongolica and Pinus densiflora dominated in under canopy layer of Darakwon. S. alnifolia which is Urban adapted species were distributed in most study areas. In terms of alien species, Magnolia obovata and Robinia pseudoacacia were newly intruded in the opened crown, and Pueraria thunbergiana was distributed in Soquicheon valley. As the result of soil analysis, acidification(pH 4.49) and low level of organic matter(3.23%), available phosphate(1.40mg/kg) and exchangeable cation were analyzed and it was considered that those environment poorly support the vegetation growth.

A Case of Carbamoyl Phosphate Synthetase 1 Deficiency with Novel Mutations in CPS1 Treated by Liver Cell Transplantation (신생아기에 새로운 CPS1 유전자 돌연변이가 확인되고, 간세포이식 시행 받은 Carbamoyl phosphatase synthetase 1 deficiency 1례)

  • Lee, Jisun;Yang, Aram;Kim, Jinsup;Park, Hyung-Doo;Lee, Sanghoon;Lee, Suk-Koo;Cho, Sung Yoon;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.17 no.1
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    • pp.31-37
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    • 2017
  • Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is an autosomal recessive disorder of the urea cycle that causes hyperammonemia. Two forms of CPS1D are recognized: a lethal neonatal type and a less severe, delayed-onset type. Neonatal CPS1D cases often present their symptoms within the first days of life. Delayed-onset cases are predominantly adolescents or adults, and infantile delayed-onset cases are rare. Severe hyperammonemia in the neonatal period leads to serious brain damage, coma, and death if not treated promptly. Therefore, early diagnosis and acute treatment are crucial. Despite the improvement of treatments, including continuous hemodialysis, ammonia-lowering agents, and a low-protein diet, the overall outcome of severe forms of hyperammonemia often remains disappointing. As the liver is the only organ in which ammonia is converted into urea, liver transplantation has been considered as an elegant and radical alternative therapy to classical dietary and medical therapies. However, liver transplantation has many disadvantages, such as a considerable risk for technical complications and perioperative metabolic derangement, especially in neonates. Additionally, there is a lack of suitable donor organs in most countries. According to recent studies, liver cell transplantation is a therapeutic option and serves as a bridge to liver transplantation. Here, we report a Korean CPS1D patient with novel mutations in CPS1 who was treated by liver cell transplantation after being diagnosed in the neonatal period and showed a good neurodevelopmental outcome at the last follow-up at six months of age.

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An Analytical Validation of the GenesWellTM BCT Multigene Prognostic Test in Patients with Early Breast Cancer (조기 유방암 환자를 위한 다지표 예후 예측 검사 GenesWellTM BCT의 분석적 성능 시험)

  • Kim, Jee-Eun;Kang, Byeong-il;Bae, Seung-Min;Han, Saebom;Jun, Areum;Han, Jinil;Cho, Min-ah;Choi, Yoon-La;Lee, Jong-Heun;Moon, Young-Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.2
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    • pp.79-87
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    • 2017
  • GenesWell$^{TM}$ BCT is a 12-gene test suggesting the prognostic risk score (BCT Score) for distant metastasis within the first 10 years in early breast cancer patients with hormone receptor-positive, HER2-negative, and pN0~1 tumors. In this study, we validated the analytical performance of GenesWell$^{TM}$ BCT. Gene expression values were measured by a one-step, real-time qPCR, using RNA extracted from FFPE specimens of early breast cancer patients. Limit of Blank, Limit of Detection, and dynamic range for each of the 12 genes were assessed by serially diluted RNA pools. The analytical precision and specificity were evaluated by three different RNA samples representing low risk group, high risk group, and near-cutoff group in accordance with their BCT Scores. GenesWell$^{TM}$ BCT could detect gene expression of each of the 12 genes from less than $1ng/{\mu}L$ of RNA. Repeatability and reproducibility across multiple testing sites resulted in 100% and 98.3% consistencies of risk classification, respectively. Moreover, it was confirmed that the potential interference substances does not affect the risk classification of the test. The findings demonstrate that GenesWell$^{TM}$ BCT have high analytical performance with over 95% consistency for risk classification.

Dielectric/piezoelectric Properties of Mn-Doped PMN-PZT with Variations of the Sintering Temperature and Addition of B2O3 (소결온도와 B2O3첨가량에 따른 Mn첨가 PMN-PZT의 유전 및 압전특성의 변화)

  • Shin Hyo-Soon
    • Journal of the Korean Ceramic Society
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    • v.41 no.9
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    • pp.709-714
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    • 2004
  • The additive of low temperature sintering in Mn-doped PMN-PZT known as high piezoelectric materials was studied in this experiment. B$_2$O$_3$ was used for the additive of low temperature sintering. The effects of sintering temperature in dielectric, and piezoelectric properties were investigated with the amounts of B$_2$O$_3$. Sintered density was increased in comparison with no addition and under 2wt% B$_2$O$_3$ and lower sintering temperature than 100$0^{\circ}C$. Therefore, in the low sintering temperature, the densification was improved by the addition of the B$_2$O$_3$. However, the sintering density was lower than that of the main composition in the case of the sintered at over 10$50^{\circ}C$. Dielectric constant with the addition of B$_2$O$_3$ was evaluated. The dielectric constant was 1000 2 wt% of B$_2$O$_3$ and sintered at 100$0^{\circ}C$. Under 2wt% of B$_2$O$_3$, the electromechanical coupling factor and the piezoelectric constant were not so much decreased. The electromechanical coupling factor and the piezoelectric constant were 50% and 300(${\times}$10$^{-12}$ C/N) respectively. The mechanical quality factor was increased with B$_2$O$_3$. The mechanical quality factor was 1700 at 0.5wt% B$_2$O$_3$ and sintered at 110$0^{\circ}C$. Dielectric loss was less than 0.5% regardless of the amount of B$_2$O$_3$.

Clinical Significance of Creatine Kinase MB mass and Cardiac Troponin I as a Marker of Perioperative Myocardial Infarction After Coronary Artery Bypass Grafting (관상동맥 우회술 후 심근경색의 표지자로서 Creatine Kinase MB 농도와 Cardiac Troponon I의 임상적 의의)

  • 이재진;김응중;이원용;신윤철;지현근
    • Journal of Chest Surgery
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    • v.35 no.1
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    • pp.27-35
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    • 2002
  • Background: A perioperative myocardial infarction(PMI) is one of the major complications after CABG. Among diagnostic methods of PMI, CK-MB activity assays have been increasingly replaced by CK-MB mass assays, which have more sensitive, simple measurement. Also, new cardiac-specific and -sensitive marker, cardiac troponin I(cTnl), has been shown to be a marker of myocardial infarction. We report our evaluation of clinical significance of CK-MB mass and cTnl as a marker of PMI after CABG. Material and Method: We studied 32 patients who underwent CABG at Kangdong Sacred Hospital between April 2000 and April 2001. Postoperative serum CK-MB activity level, serum CK-MB mass, cTnl, electrocardiogram, echocardiogram, and clinical data were recorded prospectively The diagnosis of PMI was defined as positive 2 among 3 or all of the following , by a new Q wave on the electrocardiogram, by serum CK-MB activity higher than 200 lU/L within 72 hours after operation, and by new regional wall motion abnormality on the echocardiogram. Result: After CABG, 3 patients had sustained a PMI according to current diagnostic criteria. As serum CK-MB activity time course, a level of CK-MB activity 12 hours after CABG had very linear correlated significance with serum CK-MB mass 24hours(R=0.946) and cTnl 48 hours(R=0.933) after CABG(p=0.000). As we used a receiver operating characteristics curve(ROC curve) for a diagnostic cutoff value in patients with PMI, serum CK-MB mass levels higher than 30.05 ug/L 24 hours after CABG detected the presence of PMI with an area under the ROC curve of 1.0, a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100%. Also serum cTnl levels higher than 17.15 ug/L 48 hours after CABG detected the presence of PMI with an area under the ROC curve of 0.98, a sensitivity of 100%, a specificity of 96.6%, a positive preclictive value of 75%, and a negative predictive value of 100% Conclusion: We concluded that both the measurement of CK-MB mass and cTnl are the easier, accurate methods as a diagnostic marker of PMT after CABG, also as a proposal of diagnostic cutoff value enables to an early detection of PMI. However, a 1arger number of patient will be needed because of statistic limitation that a small number of participating patients, a small number of PMI.

Removal of Cochlodinium polykrikoides using the Dredged Sediment from a Coastal Fishery (연안어장 준설퇴적물을 이용한 Cochlodinium polykrikoides 제거)

  • Sun, Young-Chul;Kim, Myoung-Jin;Song, Young-Chae;Ko, Seong-Jeong;Hwang, Eung-Ju;Jo, Q-Tae
    • Journal of Korean Society of Environmental Engineers
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    • v.32 no.1
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    • pp.53-60
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    • 2010
  • In the present study, experiments have been performed to investigate the possibility of removing Cochlodinium polykrikoides using the dredged sediment from a coastal fishery and then to derive the optimal conditions; the amount and particle size of dredged sediment besprinkled into water, the thermal treatment, the types and amounts of additives, and the depth profile of Cochlodinium polykrikoides. Results showed that the optimal amount of dredged sediment besprinkled into water was 6~10 g/L, and the removal efficiency of Cochlodinium polykrikoides after the reaction time for 60 min was 73~93%. Note that, in the real sea water, it is necessary to besprinkle 6~10 $kg/m^3$ of dry dredged sediment on a unit area (1 $m^2$). With decreasing particle size, Cochlodinium polykrikoides could be more efficiently removed. The removal efficiency was 93% with the dredged sediment smaller than 100 ${\mu}m$, whereas it was 51% with that of 100 ${\mu}m$ ${\mu}m$. Since most of dredged sediment (over 90%) was smaller than 100 ${\mu}m$, high efficiency could be obtained by besprinkling only the dredged sediment without pre-treatment. CaO was found to be an effective additive in promoting the removal efficiency (up to 99%). The optimal amount of additive was 5~10%, however, it was necessary to use as small amount of an additive as possible in order to avoid the sharp increase in pH. The removal efficiency increased with increasing depth profile of Cochlodinium polykrikoides. The removal efficiency was 83% at 5 cm depth, whereas it was 93% at 50 cm depth. In the sea water, red tide occurred within 3 m depth, and furthermore most Cochlodinium polykrikoides existed within 1 m depth. It was, therefore, expected that higher removal efficiency of Cochlodinium polykrikoides could be obtained when the dredged sediment was besprinkled into the sea water. The removal efficiency of Cochlodinium polykrikoides was up to 93% when the dredged sediment (<100 ${\mu}m$) was besprinkled into water at the ratio of 10 g/L. This result was comparable to that obtained with loess (90~97%). All the results in the present study indicated that the dredged sediment from a coastal fishery could be successfully used as a substitute of loess for removing the red tide alga.