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PLoS Medicine

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https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#1
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923049/expression-of-lncrnas-in-low-grade-gliomas-and-glioblastoma-multiforme-an-in-silico-analysis
#2
Brian J Reon, Jordan Anaya, Ying Zhang, James Mandell, Benjamin Purow, Roger Abounader, Anindya Dutta
BACKGROUND: Each year, over 16,000 patients die from malignant brain cancer in the US. Long noncoding RNAs (lncRNAs) have recently been shown to play critical roles in regulating neurogenesis and brain tumor progression. To better understand the role of lncRNAs in brain cancer, we performed a global analysis to identify and characterize all annotated and novel lncRNAs in both grade II and III gliomas as well as grade IV glioblastomas (glioblastoma multiforme [GBM]). METHODS AND FINDINGS: We determined the expression of all lncRNAs in over 650 brain cancer and 70 normal brain tissue RNA sequencing datasets from The Cancer Genome Atlas (TCGA) and other publicly available datasets...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923047/precision-cancer-diagnostics-tracking-genomic-evolution-in-clinical-trials
#3
Francisco Beca, Andrew H Beck
In a Perspective, Francisco Beca and Andrew Beck discuss Charles Swanton and colleagues' accompanying Research Article on somatic mutations in patients with inflammatory breast cancer treated in a Phase II clinical trial.
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#4
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#5
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923042/sequencing-strategies-to-guide-decision-making-in-cancer-treatment
#6
James T Topham, Marco A Marra
In a Perspective, James Topham and Marco Marra discuss progress in the use of genomic information to guide cancer treatment.
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898682/genetic-predisposition-to-an-impaired-metabolism-of-the-branched-chain-amino-acids-and-risk-of-type-2-diabetes-a-mendelian-randomisation-analysis
#7
Luca A Lotta, Robert A Scott, Stephen J Sharp, Stephen Burgess, Jian'an Luan, Therese Tillin, Amand F Schmidt, Fumiaki Imamura, Isobel D Stewart, John R B Perry, Luke Marney, Albert Koulman, Edward D Karoly, Nita G Forouhi, Rasmus J O Sjögren, Erik Näslund, Juleen R Zierath, Anna Krook, David B Savage, Julian L Griffin, Nishi Chaturvedi, Aroon D Hingorani, Kay-Tee Khaw, Inês Barroso, Mark I McCarthy, Stephen O'Rahilly, Nicholas J Wareham, Claudia Langenberg
BACKGROUND: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. METHODS AND FINDINGS: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8)...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898680/a-core-outcome-set-for-the-benefits-and-adverse-events-of-bariatric-and-metabolic-surgery-the-bariact-project
#8
Karen D Coulman, James Hopkins, Sara T Brookes, Katy Chalmers, Barry Main, Amanda Owen-Smith, Robert C Andrews, James Byrne, Jenny L Donovan, Graziella Mazza, Barnaby C Reeves, Chris A Rogers, Janice L Thompson, Richard Welbourn, Sarah Wordsworth, Jane M Blazeby
BACKGROUND: Bariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials-the BARIACT Study. METHODS AND FINDINGS: Outcomes identified from systematic reviews and patient interviews informed a questionnaire survey...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898679/patient-reported-barriers-to-adherence-to-antiretroviral-therapy-a-systematic-review-and-meta-analysis
#9
Zara Shubber, Edward J Mills, Jean B Nachega, Rachel Vreeman, Marcelo Freitas, Peter Bock, Sabin Nsanzimana, Martina Penazzato, Tsitsi Appolo, Meg Doherty, Nathan Ford
BACKGROUND: Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. METHODS AND FINDINGS: We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898678/leukocyte-telomere-length-in-relation-to-17-biomarkers-of-cardiovascular-disease-risk-a-cross-sectional-study-of-us-adults
#10
David H Rehkopf, Belinda L Needham, Jue Lin, Elizabeth H Blackburn, Ami R Zota, Janet M Wojcicki, Elissa S Epel
BACKGROUND: Leukocyte telomere length (LTL) is a putative biological marker of immune system age, and there are demonstrated associations between LTL and cardiovascular disease. This may be due in part to the relationship of LTL with other biomarkers associated with cardiovascular disease risk. However, the strength of associations between LTL and adiposity, metabolic, proinflammatory, and cardiovascular biomarkers has not been systematically evaluated in a United States nationally representative population...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898675/the-dengue-vaccine-dilemma-balancing-the-individual-and-population-risks-and-benefits
#11
Jacqueline Deen
In a Perspective, Jacqueline Deeen discusses challenges in balancing the individual and population risks and benefits for CYD-TDV (Dengvaxia), the first available dengue vaccine.
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898673/towards-equity-in-health-researchers-take-stock
#12
EDITORIAL
Annette Rid, Michael A Johansson, Gabriel Leung, Hannah Valantine, Esteban G Burchard, Sam S Oh, Cathy Zimmerman
For the 2016 end-of-the-year editorial, the PLOS Medicine editors asked 7 global health leaders to discuss developments relevant to the equitable provision of medical care to all populations. The result is a collection of expert views on ethical trial design, research during outbreaks, high-burden infectious diseases, diversity in research and protection of migrants.
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898672/lifestyle-advice-combined-with-personalized-estimates-of-genetic-or-phenotypic-risk-of-type-2-diabetes-and-objectively-measured-physical-activity-a-randomized-controlled-trial
#13
Job G Godino, Esther M F van Sluijs, Theresa M Marteau, Stephen Sutton, Stephen J Sharp, Simon J Griffin
BACKGROUND: Information about genetic and phenotypic risk of type 2 diabetes is now widely available and is being incorporated into disease prevention programs. Whether such information motivates behavior change or has adverse effects is uncertain. We examined the effect of communicating an estimate of genetic or phenotypic risk of type 2 diabetes in a parallel group, open, randomized controlled trial. METHODS AND FINDINGS: We recruited 569 healthy middle-aged adults from the Fenland Study, an ongoing population-based, observational study in the east of England (Cambridgeshire, UK)...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898668/the-long-term-safety-public-health-impact-and-cost-effectiveness-of-routine-vaccination-with-a-recombinant-live-attenuated-dengue-vaccine-dengvaxia-a-model-comparison-study
#14
Stefan Flasche, Mark Jit, Isabel Rodríguez-Barraquer, Laurent Coudeville, Mario Recker, Katia Koelle, George Milne, Thomas J Hladish, T Alex Perkins, Derek A T Cummings, Ilaria Dorigatti, Daniel J Laydon, Guido España, Joel Kelso, Ira Longini, Jose Lourenco, Carl A B Pearson, Robert C Reiner, Luis Mier-Y-Terán-Romero, Kirsten Vannice, Neil Ferguson
BACKGROUND: Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9)...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898664/will-10-million-people-die-a-year-due-to-antimicrobial-resistance-by-2050
#15
Marlieke E A de Kraker, Andrew J Stewardson, Stephan Harbarth
Marlieke de Kraker and colleagues reflect on the need for better global estimates for the burden of antimicrobial resistance.
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27875542/educational-outreach-with-an-integrated-clinical-tool-for-nurse-led-non-communicable-chronic-disease-management-in-primary-care-in-south-africa-a-pragmatic-cluster-randomised-controlled-trial
#16
Lara R Fairall, Naomi Folb, Venessa Timmerman, Carl Lombard, Krisela Steyn, Max O Bachmann, Eric D Bateman, Crick Lund, Ruth Cornick, Gill Faris, Thomas Gaziano, Daniella Georgeu-Pepper, Merrick Zwarenstein, Naomi S Levitt
BACKGROUND: In many low-income countries, care for patients with non-communicable diseases (NCDs) and mental health conditions is provided by nurses. The benefits of nurse substitution and supplementation in NCD care in high-income settings are well recognised, but evidence from low- and middle-income countries is limited. Primary Care 101 (PC101) is a programme designed to support and expand nurses' role in NCD care, comprising educational outreach to nurses and a clinical management tool with enhanced prescribing provisions...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27875535/minimally-invasive-autopsy-a-new-paradigm-for-understanding-global-health
#17
Peter Byass
Peter Byass reflects on the potential niche for minimally invasive autopsies in determining cause-of-death in low- and middle-income countries.
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27875534/seasonal-malaria-chemoprevention-an-evolving-research-paradigm
#18
Robert W Snow
Robert W. Snow discusses the importance of empirical evidence, such as that provided in the trial published this week by Milligan and colleagues, in guiding malaria control in Africa.
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27875532/willingness-to-know-the-cause-of-death-and-hypothetical-acceptability-of-the-minimally-invasive-autopsy-in-six-diverse-african-and-asian-settings-a-mixed-methods-socio-behavioural-study
#19
Maria Maixenchs, Rui Anselmo, Emily Zielinski-Gutiérrez, Frank O Odhiambo, Clarah Akello, Maureen Ondire, S Shujaat H Zaidi, Sajid Bashir Soofi, Zulfiqar A Bhutta, Kounandji Diarra, Mahamane Djitèye, Roukiatou Dembélé, Samba Sow, Pamela Cathérine Angoissa Minsoko, Selidji Todagbe Agnandji, Bertrand Lell, Mamudo R Ismail, Carla Carrilho, Jaume Ordi, Clara Menéndez, Quique Bassat, Khátia Munguambe
BACKGROUND: The minimally invasive autopsy (MIA) is being investigated as an alternative to complete diagnostic autopsies for cause of death (CoD) investigation. Before potential implementation of the MIA in settings where post-mortem procedures are unusual, a thorough assessment of its feasibility and acceptability is essential. METHODS AND FINDINGS: We conducted a socio-behavioural study at the community level to understand local attitudes and perceptions related to death and the hypothetical feasibility and acceptability of conducting MIAs in six distinct settings in Gabon, Kenya, Mali, Mozambique, and Pakistan...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27875530/validity-of-a-minimally-invasive-autopsy-for-cause-of-death-determination-in-adults-in-mozambique-an-observational-study
#20
Paola Castillo, Miguel J Martínez, Esperança Ussene, Dercio Jordao, Lucilia Lovane, Mamudo R Ismail, Carla Carrilho, Cesaltina Lorenzoni, Fabiola Fernandes, Rosa Bene, Antonio Palhares, Luiz Ferreira, Marcus Lacerda, Inacio Mandomando, Jordi Vila, Juan Carlos Hurtado, Khátia Munguambe, Maria Maixenchs, Ariadna Sanz, Llorenç Quintó, Eusebio Macete, Pedro Alonso, Quique Bassat, Clara Menéndez, Jaume Ordi
BACKGROUND: There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique...
November 2016: PLoS Medicine
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