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The life of Bagan speaks through its villages, from the founding set of nineteen some two thousand years ago, until today. This formative role of villages, however, has been side-lined by the fame of Bagan as the centre of a great Buddhist empire. The present article focuses on one village, Myinkaba. The location, its history, tangible and intangible characteristics underpin an evolving community of trade, production and religious patronage. Other villages at Bagan likewise have developed their own personalities making this analysis a proposal and potential template for bringing a new perspective to dynamics of the ancient city and its sustainable future. Like all the villages of Bagan, Myinkaba’s culture is Buddhist yet mixed with animist and other elements from the interaction of Pyu, Bamar and Mon groups over many centuries. Of the capital’s nineteen ‘founding’ villages, Myinkaba is the only one anchored on a large seasonal water body or in-gyi. The prime location on the Ayeyarawady River has enabled trade in bamboo used for lacquer and other products over many centuries. The site also contains evidence of glass production and smelting in a series of kilns. Festivals earn income for the temples, with sale of traditional snacks and a puppet competition. Inscriptions and historical links with the ‘captured’ eleventh century ruler of Thaton, King Manuha, add associations to Mon areas of Lower Myanmar. We construct a working model to encourage further village-based excavation, related research and education in future years that may also contribute to the sustenance of the UNESCO World Heritage site of Bagan. ကျေးရွာများသည် ပုဂံ၏ သမိုင်းတင်ခေတ်ဆိုင်ရာ ရှေးဟောင်းသုတေသနပညာအတွက် အရေးပါသည့်ကဏ္ဍမှ ပါဝင်သည်။ သို့သော် ပုဂံ၏ ထူးကဲသည့် အနုဗိသုကာဆိုင်ရာ လေ့လာမှုများနှင့် ယှဉ်သော် ရပ်ကျေး ရွာကျေးများအား လေ့လာမှု အလွန်နည်းပါးပါသေးသည်။ ဤစာတမ်း၌ မြင်းကပါရွာ၏ ဒြပ်ရှိ ဒြပ်မဲ့ အမွေအနှစ်များနှင့်တကွ သဘာဝရင်းမြစ်များအား အတူလွှမ်းခြုံလေ့လာ၍ သုတေသနကွင်းဆက်များအား ရည်ညွှန်းတင်ပြသွားပါမည်။ မြင်းကပါရွာသည် ပုဂံမြို့တော်၏ မူလ ၁၉ ရွာ အနက် အစဦ်အလာ ပုဂံမြို့တည်သမိုင်း၊ ကျောက်စာ၊ ဖန်ချက်လုပ်ငန်း၊ တည်ရှိနေဆဲဖြစ်သည့် ယွန်းလက်မှုအမွေအနှစ်တို့အရ မွန်နှင့် ဆက်နွယ်သည့် တစ်ခုတည်းသောရွာဖြစ်သည်ကိုသက်သေထူနေသည်။ကျောက်စာအထောက်အထားများက ၎င်းရွာ၏ ရင်းမြစ်ကြွယ်ဝမှုနှင့် အရေးပါမှုကို မီးမောင်းထိုးပြနေပါသည်။ ပထမထောင်စုနှစ်မှသည် ယခုကာလထိ ကူးသန်းရောင်းဝယ်ရေးသည် သာသန အနုဂ္ဂဟများအား တွန်းအားဖြစ်စေသည့်အချက် ၁၁ ရာစုကတည်းကတည်ရှိခဲ့သော ဘုရားစေတီအများအပြား၌ သာမက ယနေ့ခေတ် လူမှုအဖွဲ့အစည်းများ ကြောထောက်နောက်ခံပြုသည့် ဘုရားပွဲများ၌လည်း တွေ့မြင်နိုင်သည်။ မြင်းကပါ၏ ရှေးဟောင်အမွေအနှစ်နှင့် ရှင်သန်ဆဲ အမွေအနှစ်တို့သည် ရပ်ရွာ အဏု-ဒေသများ၏ ဒေသိယ ကိုယ်ပိုင်လူမှုလက္ခဏာ နှင့် ယဉ်ကျေးမှုတို့၏ အခန်းကဏ္ဍကိုသာမက ယူနက်စကို ကမ္ဘာ့အမွေအနှစ် နေရာ ရည်ရှည်တည့်တံ့ရေး စီမံခန့်ခွဲမှု၌ ၎င်းတို့၏ အရေးပါမှု ကိုလည်း မီးမောင်းထိုးပြနေသည်။

Abstract Background This retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay. Method Cell-free DNA (cfDNA) extracted from frozen plasma (N = 35) or fresh whole blood (N = 90) samples were subjected to a 62-gene hybrid capture-based next-generation sequencing assay FoundationACT. Concordance was analyzed for 51 matched FoundationACT and FoundationOne (tissue) cases. The maximum somatic allele frequency (MSAF) was used to estimate the amount of tumor fraction of cfDNA in each sample. The detection of GAs was correlated with the amount of cfDNA, MSAF, total tumor anatomic burden (dimensional sum), and total tumor metabolic burden (SUVmax sum) of the largest ten tumor lesions on PET/CT scans. Results FoundationACT detected GAs in 69 of 81 (85%) cases with MSAF > 0. Forty-two of 51 (82%) cases had ≥ 1 concordance GAs matched with FoundationOne, and 22 (52%) matched to the National Comprehensive Cancer Network (NCCN)-recommended molecular targets. FoundationACT also detected 8 unique molecular targets, which changed the therapy in 7 (88%) patients who did not have tumor rebiopsy or sufficient tumor DNA for genomic profiling assay. In all samples (N = 81), GAs were detected in plasma cfDNA from cancer patients with high MSAF quantity (P = 0.0006) or high tumor metabolic burden (P = 0.0006) regardless of cfDNA quantity (P = 0.2362). Conclusion This study supports the utility of using plasma-based genomic assays in cancer patients with high plasma MSAF level or high tumor metabolic burden.

Abstract Background Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC) who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab. Case presentation A patient with chemotherapy-refractory, metastatic lung SCC developed symptomatic pneumonitis by week 4 after nivolumab treatment, concurrently with onset of a potent antitumor response. Despite discontinuation of nivolumab after three doses and the use of high dose oral corticosteroids for grade 3 pneumonitis, continued tumor response to a complete remission by 3 months was evident by radiographic assessment. At the time of this submission, the patient has remained in clinical remission for 14 months. High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively. Tumor genomic profiling by FoundationOne targeted exome sequencing revealed a very high tumor mutation burden (TMB) corresponding to 95–96 percentile in lung SCC, i.e., 87.4–91.0 and 82.9 mut/Mb, respectively, in pre- and post-nivolumab tumor specimens. Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient’s immune system against one or more preexisting tumor-associated antigens (TAAs). One potential TAA candidate is telomerase reverse transcriptase (TERT) in which an oncogenic promoter -146C>T mutation was detected. Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been used to develop universal cancer vaccine targeting TERT-derived peptides. Conclusions Nivolumab could quickly reset and sustain host immunity against preexisting TAA(s) in this chemotherapy-refractory lung SCC patient. Further mechanistic studies are needed to characterize the effective immune cells and define the HLA-restricted TAA(s) and the specific T cell receptor clones responsible for the potent antitumor effect, with the aim of developing precision immunotherapy with improved effectiveness and safety.