Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A data‐driven approach to conditional screening of high‐dimensional variables

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133576/1/sta4115.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133576/2/sta4115_am.pd

Demand and willingness to pay for different treatment and care services among patients with heart diseases in Hanoi, Vietnam

Bach Xuan Tran,1,2 Giang Thu Vu,3 Thu Hong Thi Nguyen,4 Long Hoang Nguyen,5 Dat Dinh Pham,4 Viet Quang Truong,4 Thao Phuong Thi Thai,6 Thuc Minh Thi Vu,7 Tuan Quoc Nguyen,8 Vu Nguyen,9 Trang Huyen Thi Nguyen,10 Carl A Latkin,2 Cyrus SH Ho,11 Roger CM Ho12 1Department of Health Economics, Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam; 2Department of Health, Behavior and Society, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 3Center of Excellence in Evidence-based Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 4Hanoi Heart Hospital, Hanoi, Vietnam; 5Center of Excellence in Behavioral Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 6Department of General Planning and Department of Cardiology, Friendship Hospital, Hanoi, Vietnam; 7Tam Anh Hospital, Hanoi, Vietnam; 8Hanoi Department of Health, Hanoi, Vietnam; 9Department of Neurosurgery Spine-Surgery, Hanoi Medical University Hospital, Hanoi, Vietnam; 10Institute for Global Health Innovations, Duy Tan University, Da Nang, Vietnam; 11Department of Psychological Medicine, National University Hospital, Singapore, Singapore; 12Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Introduction: In Vietnam, cardiovascular diseases (CVDs) are serious health issues, especially in the context of overload central heart hospitals, insufficient primary healthcare, and lack of customer-oriented care and treatment. Attempts to measure demand and willingness-to-pay (WTP) for different CVD treatments and care services have been limited. This study explored the preferences and WTP of patients with heart diseases for different home- and hospital-based services in Hanoi, Vietnam. Methods: A cross-sectional survey was performed at the Hanoi Heart Hospital from July to December 2017. A contingent valuation was adopted to determine the preferences of patients and measure their WTP. Interval regressions were employed to determine the potential predictors of patients’ WTP. Results: Hospital-based services were most preferred by patients, with demand ranging from 45.6% to 82.3% of total participants, followed by home-based (45.4%–45.8%) and administrative services (28.9%–34%). WTP for hospital-based services were in the range of US$9.8 (US$ 8.4–11.2)–US$21.9 (US$ 20.3–23.4), while figures for home-based and administrative services were US$9.8 (US$ 8.4–11.2)–US$22 (US$ 18.7–25.3) and 1.9 (US 1.6–2.2)–US 7.5 (US$ 6.3–8.6), respectively. Patients who lived in urban areas, were employed, were having higher level of education, and were not covered by health insurance were willing to pay more for services, especially home-based ones. Conclusion: Demand and WTP for home-based services among heart disease patients were moderately low compared with hospital-based ones. There is a need for more policies supporting home-based services, better communication of services’ benefits to general public and patients, and introduction of services packages based on patients’ preferences. Keywords: willingness to pay, preference, heart disease, service, Vietna

Targeting breast cancer stem cells by dendritic cell vaccination in humanized mice with breast tumor: preliminary results

Phuc Van Pham,1 Hanh Thi Le,1 Binh Thanh Vu,1 Viet Quoc Pham,1 Phong Minh Le,1 Nhan Lu-Chinh Phan,1 Ngu Van Trinh,1 Huyen Thi-Lam Nguyen,1 Sinh Truong Nguyen,1 Toan Linh Nguyen,2 Ngoc Kim Phan1 1Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, 2Vietnam Military Medical University, Ha Dong, Ha Noi, Vietnam Background: Breast cancer (BC) is one of the leading cancers in women. Recent progress has enabled BC to be cured with high efficiency. However, late detection or metastatic disease often renders the disease untreatable. Additionally, relapse is the main cause of death in BC patients. Breast cancer stem cells (BCSCs) are considered to cause the development of BC and are thought to be responsible for metastasis and relapse. This study aimed to target BCSCs using dendritic cells (DCs) to treat tumor-bearing humanized mice models. Materials and methods: NOD/SCID mice were used to produce the humanized mice by transplantation of human hematopoietic stem cells. Human BCSCs were injected into the mammary fat pad to produce BC humanized mice. Both hematopoietic stem cells and DCs were isolated from the human umbilical cord blood, and immature DCs were produced from cultured mononuclear cells. DCs were matured by BCSC-derived antigen incubation for 48 hours. Mature DCs were vaccinated to BC humanized mice with a dose of 106 cells/mice, and the survival percentage was monitored in both treated and untreated groups. Results: The results showed that DC vaccination could target BCSCs and reduce the tumor size and prolong survival. Conclusion: These results suggested that targeting BCSCs with DCs is a promising therapy for BC. Keywords: breast cancer, breast cancer stem cells, targeting cancer therapy, humanized mice, targeting cancer stem cells&nbsp

Bacterial bloodstream infections in a tertiary infectious diseases hospital in Northern Vietnam: aetiology, drug resistance, and treatment outcome

Background Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam. Methods A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn ≤48 h after hospitalization or hospital acquired if >48 h. Results A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36–60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities. Conclusions Enterobacteriaceae (predominantly K. pneumoniae and E. coli) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam

Acceptability of and willingness to pay for using a smartphone-based vaccination application in a Vietnamese cohort

Bach Xuan Tran,1,2 Quang N Nguyen,3,4 Anh Kim Dang,5 Giang Thu Vu,4 Vuong Quan Hoang,6 Phuong Viet La,7 Duc Anh Hoang,8 Nhue Van Dam,9 Thu Trang Vuong,10 Long Hoang Nguyen,11 Huong Thi Le,1 Carl A Latkin,2 Cyrus SH Ho,12 Roger CM Ho11,13 1Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam; 2Department of Health, Behavior and Society, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 3Université Claude Bernard Lyon 1, Villeurbanne 69100, France; 4Center of Excellence in Evidence-based Medicine, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Vietnam; 5Institute for Global Health Innovations, Duy Tan University, Da Nang 550000, Vietnam; 6Centre for Interdisciplinary Social Research, Thanh Tay University, Hanoi, Vietnam; 7Vuong & Associates, Hanoi, Vietnam; 8Gateway International School, Hanoi, Vietnam; 9Faculty of Graduate Studies, National Economics University, Hanoi, Vietnam; 10Sciences Po Paris, Campus de Dijon, Dijon, France; 11Center of Excellence in Behavioral Medicine, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Vietnam; 12Department of Psychological Medicine, National University Hospital, Singapore 119074, Singapore; 13Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore Background: The increasing accessibility of smartphone in Vietnam shows potential in using smartphone applications for vaccination management to improve compliance. However, the acceptability and financial feasibility of using this application in Vietnam have not yet been understood. This study measured the general perception of and willingness to pay (WTP) for using smartphone-based vaccination management applications and their associated factors in Vietnam. Subjects and methods: A cross-sectional study was conducted between March and April 2016 in an urban vaccination clinic at the Hanoi Medical University in Vietnam. Convenience sampling was used to recruit 429 adult participants who had received vaccinations or whose children were vaccinated. Sociodemographic characteristics and the acceptability of and WTP for using smartphone-based vaccination management applications were evaluated. Results: Among participants who used smartphone applications, 5% were aware of existing vaccination management applications, of whom 57.9% had previously used the applications. About 69.6% of participants believed that the applications were necessary, 93.7% of them were also willing to use the applications, and 79.1% were willing to pay 92.7 thousand Vietnamese dong (VND) for the applications on average. Participants who were older, unemployed, earned more household income, and having knowledge about functions and benefits of vaccination were less likely to use the vaccination applications. Participants who brought their children to get vaccinated at younger age and with higher level of education were willing to pay more for vaccination applications. Conclusion: High levels of acceptability of, willingness to use, and WTP for smartphone-based vaccination management applications among Vietnamese participants are reported. Increased education and awareness about the benefits of vaccination and vaccination management applications through community health workers might increase the feasibility of implementing such applications and perception toward their usage among young adult smartphone users. In addition, building a stronger relationship with health care providers at hospitals might improve the application’s visibility and adoption. Keywords: WTP, feasibility, smartphone, vaccine, management, Vietna