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Glioma Immunotherapy: Advances and Challenges for Spinal Cord Gliomas
Clare Grady,Kaitlyn Melnick,Ken Porche,Farhad Dastmalchi,Daniel J. Hoh,Maryam Rahman,Ashley Ghiaseddin 대한척추신경외과학회 2022 Neurospine Vol.19 No.1
Spinal cord gliomas are rare entities that often have limited surgical options. Immunotherapy has shown promise in intracranial gliomas with some research suggesting benefit for spinal cord gliomas. A focused review of immunotherapies that have been investigated in spinal cord gliomas was performed. The primary methods of immunotherapy investigated in spinal cord gliomas include immune checkpoint inhibitors, adoptive T-cell therapies, and vaccine strategies. There are innumerable challenges that must be overcome to effectively apply immunotherapeutic strategies to the spinal cord gliomas including low incidence, few antigenic targets, the blood spinal cord barrier, the immunosuppressive tumor microenvironment and neurotoxic treatment effects. Nonetheless, research has suggested ways to overcome these challenges and treatments have been effective in case reports for metastatic non-small cell lung cancer, melanoma, midline glioma and glioblastoma. Current therapies for spinal cord gliomas are markedly limited. Further research is needed to determine if the success of immunotherapy for intracranial gliomas can be effectively applied to these unique tumors.
The Epidemiology and Etiology of Right-Sided Colonic Diverticulosis: A Review
Greg A. Turner,Michael J. O’Grady,Rachel V. Purcell,Frank A. Frizelle 대한대장항문학회 2021 Annals of Coloproctolgy Vol.37 No.4
Diverticulosis of the colon is a common condition in Western countries and most patients will remain asymptomatic, but some will present with symptoms of acute diverticulitis or bleeding. Our understanding of diverticulosis is evolving but is mostly derived from diverticulosis affecting the left-sided colon. In contrast, right-sided colonic diverticulosis (RCD) is more commonly seen in Asian countries but is much less common overall. Based on the marked differences in epidemiology, it is commonly thought that these are 2 distinct disease processes. A review of the literature describing the epidemiology and etiology of RCD was performed, with a comparison to the current understanding of left-sided diverticulosis. RCD is becoming increasingly common. The epidemiology of RCD shows it to be a mostly acquired condition, and not congenital as previously thought. Many factors in the etiology of RCD are similar to that seen in left-sided diverticulosis, with a few variations. It is therefore likely that most cases of RCD represent the same disease process that is seen in the left colon.
Heo, M.Y.,Grady, J.J.,Au, W.W. Korean Environmental Mutagen Society 1998 한국환경성돌연변이·발암원학회지 Vol.18 No.2
Exposure to environmental toxicants can cause cellular problems including the interference of DNA repair processes which may lead to the development of cancer. The existence of toxicant-induced DNA repair abnormality was investigated using mice exposed in vivo to genotoxic chemicals and then challenging their exposed lymphocytes in vitro with bleomycin. The repair of bleomycin-induced DNA damage as estimated by the frequency of chromosome aberrations was determined. Our data indicates that the observed aberration frequencies after in vivo exposure to N-methyl-N'-nitro-N-nitnsoguanidine (MNNG) and in vitro challenge with bleomycin are consistently higher than expected. The enhanced response is not due to the induction of chromosome damage by 25 or 50 mg/kg MNNG since the chemical did not cause chromosome aberrations in lymphocytes of these mice. The observed response after the combined exposure to benzo[a]pyrene (BP) and bleomycin was significantly lower than expected with low in vivo doses of BP (50 mg/kg) and then significantly higher than expected with the high doses (200 mg/kg). We interpret our data to indicate that in vivo exposure to genotoxic agents can cause abnormal DNA repair activities. The response is, however, independent of the clastogenic activities of the inducing chemicals, but dependent upon the inducing agents and on the exposure doses. 환경독성물질에 의한 폭로는 세포내 DNA의 수복과정에 영향을 미쳐 돌연변이나 암을 유발할 수 있다. 독성물질에 의해 유도된 DNA의 비정상 수복효과를 판단하기 위하여.in vivo에서 MNNG 또는 Benzo(a)pyrene을 투여하고 in vitro에서 Bleomycin을 처리하여 나타나는 염색체이상효과를 관찰하였다. 실험결과, MNNG를 투여 후 Bleomycin을 처리하였을 때 염색체이상의 상승효과가 나타났다. 한편, Benzo(a)pyrene 투여 후 Bleomycin을 처리하였을 패는 높은 농도에서 염색체이상의 상승효과가 나타났다. 이같은 결과는 MNNG나 Benzo(a)pyrene 같은 유전독성물질들이 in vivo에서 세포내 비정상 DNA수복을 일으킬 수 있으며, 이러한 작용은 관련 유전독성물질의 염색체손상성에 무관하며 투여용량에 의존되는 것으로 판단된다.
( Timothy R Angeli ),( Gregory O Grady ),( Niranchan Paskaranandavadivel ),( Jonathan C Erickson ),( Peng Du ),( Andrew J Pullan ),( Ian P Bissett ),( Leo K Cheng ) 대한소화기기능성질환·운동학회 2013 Journal of Neurogastroenterology and Motility (JNM Vol.19 No.2
Background/Aims Small intestine motility is governed by an electrical slow wave activity, and abnormal slow wave events have been associated with intestinal dysmotility. High-resolution (HR) techniques are necessary to analyze slow wave propagation, but progress has been limited by few available electrode options and laborious manual analysis. This study presents novel methods for in vivo HR mapping of small intestine slow wave activity. Methods Recordings were obtained from along the porcine small intestine using flexible printed circuit board arrays (256 electrodes; 4 mm spacing). Filtering options were compared, and analysis was automated through adaptations of the falling-edge variable- threshold (FEVT) algorithm and graphical visualization tools. Results A Savitzky-Golay filter was chosen with polynomial-order 9 and window size 1.7 seconds, which maintained 94% of slow wave amplitude, 57% of gradient and achieved a noise correction ratio of 0.083. Optimized FEVT parameters achieved 87% sensitivity and 90% positive-predictive value. Automated activation mapping and animation successfully revealed slow wave propagation patterns, and frequency, velocity, and amplitude were calculated and compared at 5 locations along the intestine (16.4 ± 0.3 cpm, 13.4 ± 1.7 mm/sec, and 43 ± 6 μV, respectively, in the proximal jejunum). Conclusions The methods developed and validated here will greatly assist small intestine HR mapping, and will enable experimental and translational work to evaluate small intestine motility in health and disease.
Sustainable Olympic Development: A Proposed Benchmark for Managing Economic Outcomes
Timothy Koba,Hua Gong,Walker J. Ross,John Grady 글로벌지식마케팅경영학회 2021 Journal of Global Sport Management Vol.6 No.1
No other sporting event possesses the grandeur of the Olympics, and few other development projects demonstrate the lack of cost containment as the Olympics which leaves local residents paying the debt and maintenance of a venue they may never use. Legacy planning is an important consideration for the hosting of the Olympics, but one that does not always receive adequate consideration resulting in the “white elephant phenomenon.” This study therefore looked to analyze the cost of hosting the Olympics compared to the economic activity in the host community in order to better inform public policy on the issues of sustainability and legacy, in particular. We are proposing a metric that helps to measure the costs that Olympic hosting has on the host community and provide a benchmark for containing those costs in terms of budgeting, construction and legacy planning for the Games. Consequently, the IOC can institute policy changes for project management that assist host cities in establishing a budget cap for venue development while simultaneously seeking to reduce the crippling debt that has accompanied them in the past.
Sun, Xiangqing,Elston, Robert C.,Barnholtz-Sloan, Jill S.,Falk, Gary W.,Grady, William M.,Faulx, Ashley,Mittal, Sumeet K.,Canto, Marcia,Shaheen, Nicholas J.,Wang, Jean S.,Iyer, Prasad G.,Abrams, Julia American Association for Cancer Research 2016 Cancer Epidemiology, Biomarkers & Prevention Vol.25 No.5
<P><B>Background:</B> Barrett's esophagus is often asymptomatic and only a small portion of Barrett's esophagus patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with Barrett's esophagus. Familial aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the increased risk of esophageal adenocarcinoma for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well developed.</P><P><B>Methods:</B> We developed a Barrett's Esophagus Translational Research Network (BETRNet) risk prediction model from 787 singly ascertained Barrett's esophagus pedigrees and 92 multiplex Barrett's esophagus pedigrees, fitting a multivariate logistic model that incorporates family history and clinical risk factors. The eight risk factors, age, sex, education level, parental status, smoking, heartburn frequency, regurgitation frequency, and use of acid suppressant, were included in the model. The prediction accuracy was evaluated on the training dataset and an independent validation dataset of 643 multiplex Barrett's esophagus pedigrees.</P><P><B>Results:</B> Our results indicate family information helps to predict Barrett's esophagus risk, and predicting in families improves both prediction calibration and discrimination accuracy.</P><P><B>Conclusions:</B> Our model can predict Barrett's esophagus risk for anyone with family members known to have, or not have, had Barrett's esophagus. It can predict risk for unrelated individuals without knowing any relatives' information.</P><P><B>Impact:</B> Our prediction model will shed light on effectively identifying high-risk individuals for Barrett's esophagus screening and surveillance, consequently allowing intervention at an early stage, and reducing mortality from esophageal adenocarcinoma. <I>Cancer Epidemiol Biomarkers Prev; 25(5); 727–35. ©2016 AACR</I>.</P>