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An Integrated Approach For Uncovering Novel DNA Methylation Biomarkers For Non-small Cell Lung Carcinoma

為了解決sc-395 ptt的問題，作者VAIBHAV KUMAR SUNKARIA 這樣論述：

Introduction - Lung cancer is one of primal and ubiquitous cause of cancer related fatalities in the world. Leading cause of these fatalities is non-small cell lung cancer (NSCLC) with a proportion of 85%. The major subtypes of NSCLC are Lung Adenocarcinoma (LUAD) and Lung Small Cell Carcinoma (LUS

C). Early-stage surgical detection and removal of tumor offers a favorable prognosis and better survival rates. However, a major portion of 75% subjects have stage III/IV at the time of diagnosis and despite advanced major developments in oncology survival rates remain poor. Carcinogens produce wide

spread DNA methylation changes within cells. These changes are characterized by globally hyper or hypo methylated regions around CpG islands, many of these changes occur early in tumorigenesis and are highly prevalent across a tumor type.Structure - This research work took advantage of publicly avai

lable methylation profiling resources and relevant comorbidities for lung cancer patients extracted from meta-analysis of scientific review and journal available at PubMed and CNKI search which were combined systematically to explore effective DNA methylation markers for NSCLC. We also tried to iden

tify common CpG loci between Caucasian, Black and Asian racial groups for identifying ubiquitous candidate genes thoroughly. Statistical analysis and GO ontology were also conducted to explore associated novel biomarkers. These novel findings could facilitate design of accurate diagnostic panel for

practical clinical relevance.Methodology - DNA methylation profiles were extracted from TCGA for 418 LUAD and 370 LUSC tissue samples from patients compared with 32 and 42 non-malignant ones respectively. Standard pipeline was conducted to discover significant differentially methylated sites as prim

ary biomarkers. Secondary biomarkers were extracted by incorporating genes associated with comorbidities from meta-analysis of research articles. Concordant candidates were utilized for NSCLC relevant biomarker candidates. Gene ontology annotations were used to calculate gene-pair distance matrix fo

r all candidate biomarkers. Clustering algorithms were utilized to categorize candidate genes into different functional groups using the gene distance matrix. There were 35 CpG loci identified by comparing TCGA training cohort with GEO testing cohort from these functional groups, and 4 gene-based pa

nel was devised after finding highly discriminatory diagnostic panel through combinatorial validation of each functional cluster.Results – To evaluate the gene panel for NSCLC, the methylation levels of SCT(Secritin), FOXD3(Forkhead Box D3), TRIM58(Tripartite Motif Containing 58) and TAC1(Tachikinin

1) were tested. Individually each gene showed significant methylation difference between LUAD and LUSC training cohort. Combined 4-gene panel AUC, sensitivity/specificity were evaluated with 0.9596, 90.43%/100% in LUAD; 0.949, 86.95%/98.21% in LUSC TCGA training cohort; 0.94, 85.92%/97.37 in GEO 66

836; 0.91,89.17%/100% in GEO 83842 smokers; 0.948, 91.67%/100% in GEO83842 non-smokers independent testing cohort. Our study validates SCT, FOXD3, TRIM58 and TAC1 based gene panel has great potential in early recognition of NSCLC undetermined lung nodules. The findings can yield universally accurate

and robust markers facilitating early diagnosis and rapid severity examination.

南海和平與衝突研究— 以2010-2022年中華民國南海政策與經略為例

為了解決sc-395 ptt的問題，作者楊媛鈞 這樣論述：

南海潛藏豐沛油氣能源與漁業資源，位處進出太平洋與印度洋要道，經濟因素和戰略地位直接影響周邊國家利益。伴隨世界經濟和戰略重心向印太地區移轉，美國為首的西方強權與中共在南海的競爭對抗，以及周邊聲索國對南海主權認知差異與利益爭奪日增，導致爭議衝突四起，影響區域穩定、安全。本研究透過和平與衝突研究途徑，檢證2010至2022年馬英九與蔡英文政府，在爭端陡升、權力不對等的國際局勢中，我國致力推動的南海政策與經略作為，並藉由深度訪談方式，套用政策分析模型，歸納中華民國如何透過戰略規劃、政策佈局與經營治理，扮演區域安全維持穩定角色。經由上述研究方法發現，我國南海政策以追求和平、發揚人道精神、開創共同利益與

相互合作為目標，冀盼運用巧實力及各樣手段與周邊國家合作，對南海衝突情勢建立和平貢獻。今年正值《聯合國海洋法公約》簽訂40週年，加上近年來美國與中共在南海區域的法律攻防戰，未來為南海開闢另一戰場的可能性極高，因此，本研究嘗試探討我國南海經營實務和運用法律途徑解決爭議，作為和平與衝突的研究案例，將其納入非暴力解決南海衝突策略，期能為新興和平研究領域注入新思維，亦成為我國政府未來面臨南海情勢變動時，政策選擇的參考依據。最後，為強化南海和平政策成效，本研究提出政策建議如下：加強我國南海主權法律效力的研究，透過多元化教育管道提升國人南海主權認同，設置國家層級之政策協調平台，並編列相關經費預算，進而爭取參

與並建構區域與國際交流、合作和協商機制，使我國南海政策更臻完善，也讓臺灣成為負責任且可為區域帶來公利、和平、穩定，提供更多貢獻的國家。