Investigation of the Trajectory of Muscle and Body Mass as a Prognostic Factor in Patients With Colorectal Cancer: Longitudinal Cohort Study

BACKGROUND: Skeletal muscle and BMI are essential prognostic factors for survival in colorectal cancer (CRC). However, there is a lack of understanding due to scarce studies on the continuous aspects of these variables. OBJECTIVE: This study aimed to evaluate the prognostic impact of the initial status and trajectories of muscle and BMI on overall survival (OS) and assess whether these 4 profiles within 1 year can represent the profiles 6 years later. METHODS: We analyzed 4056 newly diagnosed patients with CRC between 2010 to 2020. The volume of the muscle with 5-mm thickness at the third lumbar spine level was measured using a pretrained deep learning algorithm. The skeletal muscle volume index (SMVI) was defined as the muscle volume divided by the square of the height. The correlation between BMI status at the first, third, and sixth years of diagnosis was analyzed and assessed similarly for muscle profiles. Prognostic significances of baseline BMI and SMVI and their 1-year trajectories for OS were evaluated by restricted cubic spline analysis and survival analysis. Patients were categorized based on these 4 dimensions, and prognostic risks were predicted and demonstrated using heat maps. RESULTS: Trajectories of SMVI were categorized as decreased (812/4056, 20%), steady (2014/4056, 49.7%), or increased (1230/4056, 30.3%). Similarly, BMI trajectories were categorized as decreased (792/4056, 19.5%), steady (2253/4056, 55.5%), or increased (1011/4056, 24.9%). BMI and SMVI values in the first year after diagnosis showed a statistically significant correlation with those in the third and sixth years (P30 kg/m2 with a low SMVI at the time of diagnosis resulted in the highest mortality risk. We observed improved survival in patients with increased muscle mass without BMI loss compared to those with steady muscle mass and BMI. CONCLUSIONS: Profiles within 1 year of both BMI and muscle were surrogate indicators for predicting the later profiles. Continuous trajectories of body and muscle mass are independent prognostic factors of patients with CRC. An automatic algorithm provides a unique opportunity to conduct longitudinal evaluations of body compositions. Further studies to understand the complicated natural courses of muscularity and adiposity are necessary for clinical application. ©Dongjin Seo, Han Sang Kim, Joong Bae Ahn, Yu Rang Park. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 22.03.2023.ope

불균질한 스크린들, 경합하는 정체성: 주한미국공보원 문화영화와 국가상상, 1945-1972

학위논문 (박사)-- 서울대학교 대학원 : 사회학과, 2013. 2. 정근식.2차 세계대전 이후 미국은 주한미국공보원(USIS-Korea) 같은 정부 산하의 공보기구를 동맹국가에 주재시키고 장기간 선전활동을 펼쳤다. 이들 미국의 해외 당국들이 지녔던 역할에 특히 주목하면서, 본 연구는 문화영화의 제작과 소비 과정에서 한국 영화인들과 관객들이 거쳤을 정체성 협상 과정에 대해 논한다. 문화영화라는 발상은 일본의 식민통치자들에 의해 수입되었고 미국과 한국의 공보기구들에 의해 계승되었는데, 이는 주로 국가차원의 기구들이 교육과 선전을 목적으로 배포했던 영화들을 일컫는 모호한 범주였다. 공보용 다큐멘터리와 비정기적 뉴스매거진 영화, 교육용 극영화, 그리고 문화기술지 영화까지 모두 아울렀다. 따라서 문화영화는 단순히 정부 시책을 홍보하기 위한 수단이었을 뿐 아니라 문화기술지적인 요소를 통해 세계를 배우는 창구이기도 했던 것이다. 미국 공보기구들은 문화영화라는 이름으로 미국산 다큐멘터리를 수입해 미국적인 삶을 전시했고, 한국 영화인들을 고용하여 한국의 소식을 다루는 이른바 현지용 영화들을 제작하기도 했다. 냉전체제의 출현과 함께 새롭게 주어진 환경은 탈식민 국가형성기 한국인들의 정체성 형성에 결정적인 요소였다. 한국인들은 신생국가의 시민이었지만, 그들을 자유세계의 시민으로 정의한 냉전 양대 진영의 대립에 따라 그들 민족은 분할되었다. 그와 같은 맥락에서 볼 때 문화영화는 한국인들의 자아인식에 있어서 흥미로운 토대를 만들었다고 할 수 있다. 전통적인 문화기술지 영화들이 그랬던 것처럼, 세계를 배우는 창구로서의 미 공보기구 문화영화는 자아와 타자의 이분법을 습득하는 조건을 창출했다. 그러나 한국의 지정학적, 역사적 특수성 속에서 미 공보기구의 문화영화는 서로 다른 문화기술지적 응시 속에서 자아와 타자의 인식이 복잡하게 교차하는 독특한 관객성을 창출했다. 수입된 다큐멘터리들은 미국적인 삶을 이상화된 문명으로 소개했지만 한국인들이 이들 영화를 통해 미국인들과 자신을 전적으로 동일시했을 가능성은 적다. 이상화된 미국의 도시생활에 대한 표상은 오히려 이국적인 타자를 보고 즐기는 오락의 수단이었다고 할 수 있다. 자신의 삶을 구축하고 사회적, 개인적 피해로부터 재활하는 한국인들을 담은 문화영화들도 같은 시기에 제작되었다. 한국 관객들이 스스로를 자유세계의 시민으로 인식하도록 유도할 것을 목적으로 했음에도 불구하고, 그것이 주한미국공보원과 같은 외국 기구에 의해 추동된 자기인식이라는 점에서 이들 영화에는 복잡한 정체성의 문제가 나타날 수밖에 없었다. 따라서 이들 영화의 수용에는 자아와 타자를 정의하기 위한 격렬한 협상의 과정이 동반되었을 것임을 추측할 수 있다. 이러한 귀결은 미국 공보활동의 현지화 프로젝트가 낳은 필연적 결과로 볼 수 있지만, 현지 영화인의 고용이 그러한 불균질한 스크린을 창출한 단 하나의 원인이라고는 할 수 없다. 주한미국공보원으로부터 상당한 영향을 받고 제작된 국립영화제작소의 대표작 (1967)에서 나타나는 이상적 시민의 번역되고 개조된 모습과 이에 대한 한국 대중의 열광적인 호응은, 문화적 냉전의 본래 기획이 현지의 맥락에 따라 어떻게 토착화된 방식으로 변형되었는지를 잘 보여준다. 미국 공보기구에 몸을 담았던 한국 영화인들의 경우 정체성 협상의 면모는 더욱 두드러지게 나타난다. 그들은 미국 정부기구에 고용되어 자유세계 영화의 전달자 역할을 했지만, 동시에 스스로를 자국의 국가 건설자로 인식하기도 했다. 또한 그들은 단순히 고용주들의 수사를 전달하는 것이 아니라 그들 자신의 예술적 감수성을 표출하는 예술가로 스스로를 간주했다. 이처럼 경합하는 자아정체성들은 이들 영화인들에게 일정한 타협지점을 선택하도록 이끌었다. 두 명의 상징적인 다큐멘터리 제작자 로버트 플래허티와 존 그리어슨이 취했던 서로 다른 선택지가 보여주듯이, 정부의 지원을 받는 다큐멘터리 제작은 영화인들을 인문주의적 자극을 추동하는 낭만주의적 성향과 사회개조를 추구하는 계몽주의적 성향 사이에서 선택의 기로에 놓이게 하곤 했다. 주한미국공보원과 유엔한국재건단(UNKRA)에서 활동했던 한국영화인들도 비슷한 내적 갈등을 겪었는데, 이는 한국의 지정학적 조건과 결부되면서 작가주의라는 독특한 형태로 귀결되었다. 미국식 영화 훈련소를 거쳐간 이들 영화인들이 택했던 경로는 격렬한 정체성 협상의 과정에서 취할 수 있는 몇 가지 선택지를 보여준다. 미 공보기구를 떠나서 영화 작가주의를 추구하는 길, 작가주의적 지향을 지니고 있지만 깊은 회의감 속에서 이를 포기하고 대중적인 상업영화를 제작하며 살아가는 길, 그리고 미 공보기구에 남아 문화영화를 제작하면서 일말의 작가주의적 접근을 시도하는 길이 그것이다. 이들은 또한 미국이 주도하는 공보기구에서 혜택 받은 한국 영화인들이 지녔던 양가적 태도, 즉 서구 문화의 계승자이면서 동시에 비판자이기도 했던 태도를 잘 보여주고도 있다. 다시 말해 이들 영화인들은 그리어슨적인 사명과 예술가로서의 자아실현 사이, 그리고 자국의 국가건설과 자유세계의 진영건설이라는 지향 사이에서 끊임없이 타협점을 찾아야만 했으며, 이는 헤게모니적인 외국 기구가 창출해놓은 전문가 시스템이라는 조건 속에서 비롯되었다.After the Second World War, government-level public information agencies in the U.S., such as the U.S. Information Service (USIS), resided in allied nations, such as South Korea, to engage in long-term propaganda activities. This study focuses on the negotiation of identity of South Korean filmmakers and audiences in making and consuming cultural films, devoting particular attention to the role of the American foreign authorities. The idea of cultural film (Kulturfilm), which had been imported by the Japanese colonial rulers and was succeeded by the U.S. and ROK public information agencies. It was a vaguely defined category of films mainly distributed by governmental-level agencies for educational and propaganda purposes. The category of cultural film included public information documentaries, occasional newsmagazine films, ethnographic films, and educational feature films. Cultural films were not only a means of publicizing governmental policies, but also a window through which to learn about the world with an ethnographic element. Under the name of cultural film, U.S. public information agencies imported American-made documentary films which depicted the American way of life and produced localized films dealing with local issues by hiring Korean filmmakers. For Koreans who were situated in the postcolonial state formation, the new conditions fostered through the emergence of the Cold War system were crucial to their identity formation. They were citizens of a newly built state, but their nation was divided between the Cold War Power blocs which defined South Koreans as citizens of the Free World. Cultural films created an interesting foundation for South Koreans perception of the Self in this context. As a window to learn the world, cultural films of U.S. public information agencies made a condition for the Self/Other opposition, as conventional ethnographic films usually did. However, in the geopolitical and historical particularity of South Korea, those cultural films created a unique type of spectatorship that mediated the perceptions of the Self and the Other in an intricate web of different ethnographic gazes. Imported documentaries showed the American life as an idealized model of civilization, but there is little probability that Koreans fully identified themselves with Americans in these films. (Re)presentations of idealized American urban life were rather a means of entertainment to see the exotic Other. At the same time, locally made cultural films depicted South Koreans who constructed their lives and rehabilitated from social and personal damages. Despite the aim to facilitate self-recognition of Korean audiences as citizens of the Free World, such films also presented the complexity in identification since their self-recognition was organized by the foreign agencies like USIS-Korea. Thus, it is highly probable that the reception of those films was a process of intense negotiation to define the Self and the Other. This outcome was partly an inevitable consequence of the localization project of U.S. public information activitieshowever, use of local manpower was not the only cause of such an uneven screen. The appearance of translated and modified ideal citizens in Paldogangsan (1967), one of the representative films of NFPC also made under the profound impact of USIS, and an enthusiastic response from the Korean public to that film show how an original project on the cultural cold war could be transformed into a vernacular one in the more local context. In the case of Korean filmmakers who were affiliated with U.S. public information agencies, the negotiation of identity appears more clearly. They were hired by the U.S. governmental agencies and served as messengers of the Free World screen, but, at the same time, they recognized themselves as builders of the nation. Further, they also regarded themselves as individual artists who did not merely deliver rhetoric of their hirers but also expressed their own artistic sensibility. These contested self-identities led the filmmakers to adopt certain compromising positions. As one can see in the distinction between the routes of the two symbolic documentarists, Robert Flaherty and John Grierson, government-sponsored documentary filmmaking would drive filmmakers to a crossroads between romanticism facilitating humanist impulse and enlightenment seeking social engineering. Similar inner conflict of USIS- and UNKRA-affiliated filmmakers was joined together with the geopolitical conditions of South Korea and concluded with unique auteurism in film making. The routes of these alumni of the American film training camps indicate several different choices in the intense negotiations on identity: leaving the camp and devoting oneself to auteurism in filmmakingleaving the camp and keeping auteurist impulse in mind, but giving it up in commercial filmmaking with deep skepticismand remaining in the camp with auteurism in cultural film making. They also show double-sidedness of those Korean filmmakers who did receive benefits from U.S.-led agencies, as the successor and criticizer of the Western culture. They constantly had to seek compromises between the Griersonian missions and artistic self-realization and between nation-building and Free World bloc building, in an all too expert system created by a hegemonic foreign agency.Abstract i List of Abbreviations xi List of Figures xiii List of Tables xv List of Appendices xv Introduction 1 1. Problematizing the Cultural Film Production of USIS-Korea 3 2. Theoretical Background of the Study 6 3. Object of the Study: The Negotiated Korean Self 16 4. Review of Precedent Literature 18 5. Theoretical Methods and Concepts 21 6. Thesis Organization 26 Part I. The Undifferentiated Self Facing A Bullet Screen 29 Chapter 1. The Unsighted Shooter: History of the U.S. Public Information Agencies, 1945-1950 31 1. The Colonial Legacy, August, 1945 – April, 1946 33 2. Establishment of a System, April, 1946 – December, 1946 39 3. A New Condition for Differentiation, January, 1947 – August, 1948 45 4. Transfer of the Function, September, 1948 – June, 1950 51 5. Aimed Shots: The People Vote and The Choe In-kyu Production 55 Chapter 2. Show Them Where They Belong: U.S. Information Agencies Films 62 1. Sensing Society, Viewing Power: Newsreels 63 2. Introducing a Free World Superpower: WWII Films 67 3. The Birth of A Nation Reloaded: (Re)Presentation of Liberty Bell 72 4. Education for Free World Citizenship 77 5. Landscape of South Korea: The Ethnographic Korean Self 82 Chapter 3. Movie Comes to the Village: Film Spectatorship and The Negotiation of Identity 89 1. Opening of Local Information Centers and Election Education 92 2. Organization and Operation of the Mobile Education Units 97 3. Rural Audiences and the Spectatorship of Movie-Coming 100 Part II. Gazing At the Rehabilitating Self 108 Chapter 4. Innovation through War and Reconstruction: USIS and UNKRA, 1950-1958 110 1. The Korean War, and USIS-Koreas New Film Studio, June, 1950 – July, 1953 111 2. The Eisenhower Administration and the Yi Sŭng-man Government, January, 1953 – April, 1960 117 3. UNKRAs Rehabilitation Project for the Film Industry, December, 1950 – July, 1958 120 Chapter 5. The Rehabilitating Self: Troubles, Aleatory Solutions, and Restored Everyday Life 126 1. Cinematic (Re)Presentation of the Reconstruction of Korea 128 1) The Rehabilitating Subjects in Trouble, and Aleatory Solutions Through the U.S. 131 2) Intellectuals Who Accompanied Americans 135 3) Younger Generations Open to the American System 138 4) The U.S. as an Immanent External Party in the Formation of the Self 141 2. Protestant Ethics in Semi-Documentaries 143 1) Representation of Nurses: From Women in the Vanguard to Christian White Angels 143 2) Restored Everyday Life: A Peaceful Village With Rebuilt Churches 147 Chapter 6. Contested Identity: Affiliated Korean Filmmakers and Auteurist Impulse 150 1. USIS-Koreas Material Resources and Conditions for Korean Filmmakers 151 2. The Complicated Status of USIS-Affiliated Korean Filmmakers 156 3. Auteurism and the Discourses of Korean Cinema in the Germinating Period of Korean Cinema 161 4. Disharmony between Motion Picture Unit Filmmakers and UNKRA Officials 172 Chapter 7. Who Watches Whom?: Repetitive Self-Gazing and the Ethnographic Other 177 1. Spectators of Rehabilitation Films and Their Self-Gazing 178 1) Angels on the Street: Who watches whom? 178 2) The Lighthouse on the Street: Infiltrating Screens and Repetitive Self-gazing 182 3) Hyangninwŏn: A Crossing between the Colony and the Postcolony 185 2. Discovery of Korean Traditional Culture and Cultural Hierarchy in Asia 186 1) Kim Paek-pong Live: Recognition of Cultural Peculiarities 187 2) Korean Cultural Goodwill Mission Southeast Asian Tour and Its USIS Film 190 3) Visualization of a Cold War Asia as the Technology of Government 196 Part III. The Translated Self 200 Chapter 8. From Institutionalization to Closure: USIS, 1958-1972 202 1. A Dissonance between Liberty News and the ROK Government, 1958 – 1960 204 2. Institutionalization of Public Information Film Activities, 1961 – 1968 209 3. Changing Surroundings: The Nixon Doctrine, and the Yusin Regime in South Korea, 1969 – 1973 213 Chapter 9. Escapeways: Democracy Education and Expert Systems 217 1. Democracy Education and the Strategy of Visualization 219 2. Film Festivals and Auteurism in Cultural Film Production 224 3. Fostering Korean Expertise on America and Being American Experts on Korea 235 Chapter 10. Building the Self Through Translation: Exchange Programs and Intellectuals 245 1. Translation of the Local as an American Democratic Value 248 1) Localism and U.S. Public Information Films 248 2) American Films on Local Newspapers, and Korean Editor 250 2. Intellectuals and the New World: An Exhibition of Technological Development and Industrial Tourist Films 255 1) Introducing America: Korean Students Studying in America and the Imaginative Geography of Korea-America Today 255 2) Building a High Intellectual Society and Global Hierarchy of Regions 259 Chapter 11. Defining Koreanness?: Paldogangsan and the Idealized Self 264 1. Performed Localism, Translated Federalism 266 2. My Car Modernity: Nuclear Family, Highway, and Liberty 271 3. Old Korean Men Modernized: Harabŏji and Hŭi-kap 277 4. Paldogangsan and Its Aftermath 279 Conclusion 283 Bibliography 293 Appendices 318 국문초록 325Docto

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BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling

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Magnetofluoro-Immunosensing Platform Based on Binary Nanoparticle-Decorated Graphene for Detection of Cancer Cell-Derived Exosomes

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Extracellular vesicle and particle isolation from human and murine cell lines, tissues, and bodily fluids

We developed a modified protocol, based on differential ultracentrifugation (dUC), to isolate extracellular vesicles and particles (specifically exomeres) (EVPs) from various human and murine sources, including cell lines, surgically resected tumors and adjacent tissues, and bodily fluids, such as blood, lymphatic fluid, and bile. The diversity of these samples requires robust and highly reproducible protocols and refined isolation technology, such as asymmetric-flow field-flow fractionation (AF4). Our isolation protocol allows for preparation of EVPs for various downstream applications, including proteomic profiling. For complete details on the use and execution of this protocol, please refer to Hoshino et al. (2020).ope

Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation

The heterogeneity of exosomal populations has hindered our understanding of their biogenesis ; molecular composition ; biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4) ; we identified two exosome subpopulations (large exosome vesicles ; Exo-L ; 90-120 nm; small exosome vesicles ; Exo-S ; 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia ; microtubule and coagulation proteins as well as specific pathways ; such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways ; and mitotic spindle and IL-2/STAT5 signalling pathways ; respectively. Exo-S ; Exo-L and exomeres each had unique N-glycosylation ; protein ; lipid ; DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns ; suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.ope

Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer

Most breast cancer deaths are caused by metastasis and treatment options beyond radiation and cytotoxic drugs, which have severe side effects, and hormonal treatments, which are or become ineffective for many patients, are urgently needed. This study reanalyzed existing data from three genome-wide association studies (GWAS) using a novel computational biostatistics approach (muGWAS), which had been validated in studies of 600-2000 subjects in epilepsy and autism. MuGWAS jointly analyzes several neighboring single nucleotide polymorphisms while incorporating knowledge about genetics of heritable diseases into the statistical method and about GWAS into the rules for determining adaptive genome-wide significance. Results from three independent GWAS of 1000-2000 subjects each, which were made available under the National Institute of Health's "Up For A Challenge" (U4C) project, not only confirmed cell-cycle control and receptor/AKT signaling, but, for the first time in breast cancer GWAS, also consistently identified many genes involved in endo-/exocytosis (EEC), most of which had already been observed in functional and expression studies of breast cancer. In particular, the findings include genes that translocate (ATP8A1, ATP8B1, ANO4, ABCA1) and metabolize (AGPAT3, AGPAT4, DGKQ, LPPR1) phospholipids entering the phosphatidylinositol cycle, which controls EEC. These novel findings suggest scavenging phospholipids as a novel intervention to control local spread of cancer, packaging of exosomes (which prepare distant microenvironment for organ-specific metastases), and endocytosis of β1 integrins (which are required for spread of metastatic phenotype and mesenchymal migration of tumor cells). Beta-cyclodextrins (βCD) have already been shown to be effective in in vitro and animal studies of breast cancer, but exhibits cholesterol-related ototoxicity. The smaller alpha-cyclodextrins (αCD) also scavenges phospholipids, but cannot fit cholesterol. An in-vitro study presented here confirms hydroxypropyl (HP)-αCD to be twice as effective as HPβCD against migration of human cells of both receptor negative and estrogen-receptor positive breast cancer. If the previous successful animal studies with βCDs are replicated with the safer and more effective αCDs, clinical trials of adjuvant treatment with αCDs are warranted. Ultimately, all breast cancer are expected to benefit from treatment with HPαCD, but women with triple-negative breast cancer (TNBC) will benefit most, because they have fewer treatment options and their cancer advances more aggressively.ope

Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis

Tumor-secreted extracellular vesicles (EVs) are critical mediators of intercellular communication between tumor cells and stromal cells in local and distant microenvironments. Accordingly ; EVs play an essential role in both primary tumor growth and metastatic evolution. EVs orchestrate multiple systemic pathophysiological processes ; such as coagulation ; vascular leakiness ; and reprogramming of stromal recipient cells to support pre-metastatic niche formation and subsequent metastasis. Clinically ; EVs may be biomarkers and novel therapeutic targets for cancer progression ; particularly for predicting and preventing future metastatic development.ope