Author: "John Thompson" - Searchworks@Jio Institute Digital Library Search Results

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1. Development and Usability of the OHiFamily Mobile App to Enhance Accessibility to Maternal and Infant Information for Expectant Families in Ohio: Qualitative Study

Author: Natalie Perme, Endia Reid, Macdonald Chinwenwa Eluagu, John Thompson, Courtney Hebert, Steven Gabbe, and Christine Marie Swoboda
Subjects: Medicine
Abstract: BackgroundThe Infant Mortality Research Partnership in Ohio is working to help pregnant individuals and families on Medicaid who are at risk for infant mortality and preterm birth. As part of this initiative, researchers at The Ohio State University worked to develop a patient-facing mobile app, OHiFamily, targeted toward, and created for, this population. To address the social determinants of health that can affect maternal and infant health, the app provides curated information on community resources, health care services, and educational materials in a format that is easily accessible and intended to facilitate contact between families and resources. The OHiFamily app includes 3 distinct features, that is, infant care logging (eg, feeding and diaper changes), curated educational resources, and a link to the curated Ohio resource database (CORD). This paper describes the development and assessment of the OHiFamily app as well as CORD. ObjectiveThis study aimed to describe the development of the OHiFamily mobile app and CORD and the qualitative feedback received by the app’s intended audience. MethodsThe researchers performed a landscape analysis and held focus groups to determine the resources and app features of interest to Ohio families on Medicaid. ResultsParticipants from several focus groups were interested in an app that could offer community resources with contact information, information about medical providers and information and ways to contact them, health tips, and information about pregnancy and infant development. Feedback was provided by 9 participants through 3 focus group sessions. Using this feedback, the team created a curated resource database and mobile app to help users locate and access resources, as well as access education materials and infant tracking features. ConclusionsOHiFamily offers a unique combination of features and access to local resources for families on Medicaid in Ohio not seen in other smartphone apps.
Published: 2024
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2. A Peregrinação a Sand Hill Road: Investimento de capital de risco em startups de tecnologia relacionadas ao setor editorial

Author: John Thompson
Subjects: startups de tecnologia, capital de risco, publicação, Silicon Valley, Sand Hill Road, Social Sciences
Abstract: Muitos empreendedores no mundo das startups de tecnologia buscam financiamento de capital de risco para estabelecer e expandir seus negócios, mas esse pode ser um processo repleto de desafios e carregado de consequências a longo prazo. A maioria das tentativas de obter financiamento de capital de risco falhará, e a maioria das startups financiadas por capital de risco não terá sucesso. Além disso, as startups que conseguirem esse tipo de financiamento tenderão a seguir uma trajetória de desenvolvimento muito diferente da de muitas empresas tradicionais. Este artigo busca esclarecer a relação única e especial entre o capital de risco e as startups de tecnologia, com foco em um subconjunto específico: aquelas relacionadas à indústria editorial de livros. A análise abrange tanto a perspectiva de um capitalista de risco bem estabelecido no Vale do Silício e financiador de startups de tecnologia, quanto a perspectiva dos empreendedores que buscam garantir financiamento de capital de risco. Ao examinar essa relação sob ambas as óticas, podemos entender por que alguns empreendedores conseguem captar recursos enquanto outros não. Também podemos compreender por que as trajetórias de desenvolvimento das startups financiadas por capital de risco são significativamente diferentes das de muitas empresas tradicionais e explicar por que algumas dessas empresas financiadas por capital de risco falham, enquanto outras, competindo em um mercado semelhante e em condições aparentemente equivalentes, sobrevivem e prosperam.
Published: 2024
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3. Backhaul-Aware UAV-Aided Capacity Enhancement in Mixed FSO-RF Network

Author: Muhammad Nafees, Shenjie Huang, John Thompson, and Majid Safari
Subjects: Beyond fifth-generation (B5G), free-space optical (FSO) communication, millimeter wave (mmWave), unmanned aerial vehicle (UAV), Telecommunication, TK5101-6720, Transportation and communications, HE1-9990
Abstract: Future networks are expected to make substantial use of unmanned aerial vehicles (UAVs) as aerial base stations (BSs). The backhauling of UAVs is often considered with license-free and highbandwidth free-space optical (FSO) communication. Employing UAVs and FSO technology together is appropriate for numerous applications such as user offloading, network capacity enhancement, and relaying services. However, the reliability of the backhaul FSO link can be jeopardized by infrequent adverse weather conditions such as fog. In this study, we proposed the capacity enhancement of a ground BS (GBS) with the aid of an FSO-backhualed UAV aerial BS. In particular, we optimize the UAV’s circular trajectory and parameters (i.e., coverage radius and beamwidth) to maximize the total network throughput during both normal and adverse weather (e.g., fog events). Two trajectories, namely rate maximization (RMT) and fairness-constrained rate maximization (FRMT), are considered. A novel expression for the average capacity of the FSO backhaul over the entire trajectory is derived. The formulated problem aims to maximize the average network throughput with constraints pertaining to backhaul capacity, network fairness, and UAV parameters. It is shown that the UAV changes its trajectory using its coverage radius and directional antenna beamwidth according to the weather conditions and fairness requirements to maximize the total system capacity. Furthermore, real weather data from the cities of Edinburgh and London in the U.K. is used to evaluate the performance of the system under low-visibility conditions. The numerical results show the proposed FSO-backhauled UAV can provide significant capacity enhancement even in thin, light, and moderately foggy conditions.
Published: 2024
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4. A mobile health application for patients eligible for statin therapy: app development and qualitative feedback on design and usability

Author: Weidan Cao, Lang Li, Puneet Mathur, John Thompson, and M. Wesley Milks
Subjects: Statin intolerance, Mobile health application, Symptom logging, Doctor-patient communication, Disease co-management, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Abstract Background Cardiovascular disease is the leading cause of death in the United States (US). Despite the well-recognized efficacy of statins, statin discontinuation rates remain high. Statin intolerance is a major cause of statin discontinuation. To accurately diagnose statin intolerance, healthcare professionals must distinguish between statin-associated and non-statin-associated muscle symptoms, because many muscle symptoms can be unrelated to statin therapy. Patients’ feedback on muscle-related symptoms would help providers make decisions about statin treatment. Given the potential benefits and feasibility of existing apps for cardiovascular disease (CVD) management and the unmet need for an app specifically addressing statin intolerance management, the objectives of the study were 1) to describe the developmental process of a novel app designed for patients who are eligible for statin therapy to lower the risk of CVD; 2) to explore healthcare providers’ feedback of the app; and 3) to explore patients’ app usage experience. Methods The app was developed by an interdisciplinary team. Healthcare provider participants and patient participants were recruited in the study. Providers were interviewed to provide their feedback about the app based on screenshots of the app. Patients were interviewed after a 30 days of app usage. Results The basic features of the app included symptom logging, vitals tracking, patient education, and push notifications. Overall, both parties provided positive feedback about the app. Areas to be improved mentioned by both parties included: the pain question asked in symptom tracking and the patient education section. Both parties agreed that it was essential to add the trend report of the logged symptoms. Conclusions The results indicated that providers were willing to use patient-reported data for disease management and perceived that the app had the potential to facilitate doctor-patient communication. Results also indicated that user engagement is the key to the success of app efficacy. To promote app engagement, app features should be tailored to individual patient’s needs and goals. In the future, after it is upgraded, we plan to test the app usability and feasibility among a more diverse sample.
Published: 2023
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5. Educational strategies in the health professions to mitigate cognitive and implicit bias impact on decision making: a scoping review

Author: John Thompson, Helena Bujalka, Stephen McKeever, Adrienne Lipscomb, Sonya Moore, Nicole Hill, Sharon Kinney, Kwang Meng Cham, Joanne Martin, Patrick Bowers, and Marie Gerdtz
Subjects: Cognitive bias, Implicit bias, Tertiary education, Assessment, Healthcare education, Clinical decision-making, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background Cognitive and implicit biases negatively impact clinicians’ decision-making capacity and can have devastating consequences for safe, effective, and equitable healthcare provision. Internationally, health care clinicians play a critical role in identifying and overcoming these biases. To be workforce ready, it is important that educators proactively prepare all pre-registration healthcare students for real world practice. However, it is unknown how and to what extent health professional educators incorporate bias training into curricula. To address this gap, this scoping review aims to explore what approaches to teaching cognitive and implicit bias, for entry to practice students, have been studied, and what are the evidence gaps that remain. Methods This scoping review was guided by the Joanna Briggs Institute (JBI) methodology. Databases were searched in May 2022 and included CINAHL, Cochrane, JBI, Medline, ERIC, Embase, and PsycINFO. The Population, Concept and Context framework was used to guide keyword and index terms used for search criteria and data extraction by two independent reviewers. Quantitative and qualitative studies published in English exploring pedagogical approaches and/or educational techniques, strategies, teaching tools to reduce the influence of bias in health clinicians' decision making were sought to be included in this review. Results are presented numerically and thematically in a table accompanied by a narrative summary. Results Of the 732 articles identified, 13 met the aim of this study. Most publications originated from the United States (n=9). Educational practice in medicine accounted for most studies (n=8), followed by nursing and midwifery (n=2). A guiding philosophy or conceptual framework for content development was not indicated in most papers. Educational content was mainly provided via face-to-face (lecture/tutorial) delivery (n=10). Reflection was the most common strategy used for assessment of learning (n=6). Cognitive biases were mainly taught in a single session (n=5); implicit biases were taught via a mix of single (n=4) and multiple sessions (n=4). Conclusions A range of pedagogical strategies were employed; most commonly, these were face-to-face, class-based activities such as lectures and tutorials. Assessments of student learning were primarily based on tests and personal reflection. There was limited use of real-world settings to educate students about or build skills in biases and their mitigation. There may be a valuable opportunity in exploring approaches to building these skills in the real-world settings that will be the workplaces of our future healthcare workers.
Published: 2023
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6. Open Reduction Internal Fixation vs Primary Arthrodesis for Lisfranc Fracture-Dislocations: A Cost Analysis

Author: Arinze Ochuba BS, Christopher J. Murdock MD, Amy L. Xu BS, Morgan Snow BA, Jessica Schmerler BS, Christopher R. Leland MD, Claire McDaniel MD, John Thompson MD, and Amiethab A. Aiyer MD
Subjects: Orthopedic surgery, RD701-811
Abstract: Background: Lisfranc fracture-dislocation is an uncommon but serious injury that currently lacks universal consensus on optimal operative treatment. Two common fixation methods are open reduction and internal fixation (ORIF) and primary arthrodesis (PA). The objective of this study is to analyze the cost difference between ORIF and PA of Lisfranc injuries, along with the contribution of medical services to overall costs. Methods: This was a retrospective cost analysis of the MarketScan database from 2010 to 2020. MarketScan is an insurance and commercial claims database that integrates deidentified patient information. It captures person-specific clinical utilization, expenditures, and enrollment across inpatient and outpatient services. Patients undergoing primary ORIF ( CPT code 28615) vs PA (28730 and 28740) for Lisfranc fracture-dislocation were identified. The primary independent variable was ORIF vs PA of Lisfranc injury. Total costs due to operative management was the primary objective. The utilization of and costs contributed by medical services was a secondary outcome. Results: From 2010 to 2020, a total of 7268 patients underwent operative management of Lisfranc injuries, with 5689 (78.3%) ORIF and 1579 (21.7%) PA. PA was independently associated with increased net and total payment and coinsurance, clinic visits, and imaging, and patients attended significantly more PT sessions. Conclusion: Using this large database that does not characterize severity or extent of injury, we found that treatment of Lisfranc fracture-dislocation with ORIF was associated with substantially lower initial episode of treatment costs compared with PA. Specific excessive cost drivers for PA were clinic visits, PT sessions, and imaging. Level of Evidence: Level III, retrospective cohort study.
Published: 2024
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7. Scoping article: research frontiers on the governance of the Sustainable Development Goals

Author: Thomas Hickmann, Frank Biermann, Carole-Anne Sénit, Yixian Sun, Magdalena Bexell, Mitzi Bolton, Basil Bornemann, Jecel Censoro, Aurelie Charles, Dominique Coy, Frederik Dahlmann, Mark Elder, Felicitas Fritzsche, Thiago Gehre Galvão, Jarrod Grainger-Brown, Cristina Inoue, Kristina Jönsson, Montserrat Koloffon Rosas, Kerstin Krellenberg, Enayat Moallemi, Ivonne Lobos Alva, Shirin Malekpour, Dianty Ningrum, Aneliya Paneva, Lena Partzsch, Rodrigo Ramiro, Rob Raven, Eszter Szedlacsek, John Thompson, Melanie van Driel, Jéssica Viani Damasceno, Robert Webb, and Sabine Weiland
Subjects: 2030 Agenda, goal-setting, governance, implementation, policies, Sustainable Development Goals (SDGs), United Nations, Environmental sciences, GE1-350
Abstract: Abstract Non-Technical Summary This article takes stock of the 2030 Agenda and focuses on five governance areas. In a nutshell, we see a quite patchy and often primarily symbolic uptake of the global goals. Although some studies highlight individual success stories of actors and institutions to implement the goals, it remains unclear how such cases can be upscaled and develop a broader political impact to accelerate the global endeavor to achieve sustainable development. We hence raise concerns about the overall effectiveness of governance by goal-setting and raise the question of how we can make this mode of governance more effective. Technical Summary A recent meta-analysis on the political impact of the Sustainable Development Goals (SDGs) has shown that these global goals are moving political processes forward only incrementally, with much variation across countries, sectors, and governance levels. Consequently, the realization of the 2030 Agenda for Sustainable Development remains uncertain. Against this backdrop, this article explores where and how incremental political changes are taking place due to the SDGs, and under what conditions these developments can bolster sustainability transformations up to 2030 and beyond. Our scoping review builds upon an online expert survey directed at the scholarly community of the ‘Earth System Governance Project’ and structured dialogues within the ‘Taskforce on the SDGs’ under this project. We identified five governance areas where some effects of the SDGs have been observable: (1) global governance, (2) national policy integration, (3) subnational initiatives, (4) private governance, and (5) education and learning for sustainable development. This article delves deeper into these governance areas and draws lessons to guide empirical research on the promises and pitfalls of accelerating SDG implementation. Social Media Summary As SDG implementation lags behind, this article explores 5 governance areas asking how to strengthen the global goals.
Published: 2024
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8. What Protects the Autonomy of the Federal Statistical Agencies? An Assessment of the Procedures in Place to Protect the Independence and Objectivity of Official U.S. Statistics

Author: Constance F. Citro, Jonathan Auerbach, Katherine Smith Evans, Erica L. Groshen, J. Steven Landefeld, Jeri Mulrow, Thomas Petska, Steve Pierson, Nancy Potok, Charles J. Rothwell, John Thompson, James L. Woodworth, and Edward Wu
Subjects: Autonomy, Federal statistical agency, Government statistics, Independence, Official statistics, Trust, Political institutions and public administration (General), JF20-2112, Probabilities. Mathematical statistics, QA273-280
Abstract: AbstractWe assess the professional autonomy of the 13 principal U.S. federal statistical agencies. We define six components or measures of such autonomy and evaluate each of the 13 principal statistical agencies according to each measure. Our assessment yields three main findings: (a) Challenges to the objectivity, credibility, and utility of federal statistics arise largely as a consequence of insufficient autonomy. (b) There is remarkable variation in autonomy protections and a surprising lack of statutory protections for many agencies for many of the proposed measures. (c) Many existing autonomy rules and guidelines are weakened by unclear or unactionable language. We conclude that a lack of professional autonomy unduly exposes the principal federal statistical agencies to efforts to undermine the objectivity of their products and that agencies cannot completely rebuff these efforts. Our main recommendations are to strengthen the role of the OMB Chief Statistician and to legislate new statutory autonomy protections, including explicit authorization for the principal federal statistical agencies that currently have no recognition in statute. We also recommend periodic assessments of the health of the federal statistical system, including not only autonomy protections and resources, but also how well agencies are satisfying data needs for the public good and using best methods to do so.
Published: 2023
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9. How Do Hybrid School Leaders Measure Program Success? Experimental Evidence from a National Sample of Hybrid Schools. EdWorkingPaper No. 24-997

Author: Annenberg Institute for School Reform at Brown University, Matthew H. Lee, John Thompson, and Eric Wearne
Abstract: Hybrid school enrollments are trending up and many parents express a diverse range of reasons for enrolling their children in hybrid schools. Yet little is known about the pedagogical goals pursued by hybrid schools. We aim to help close this gap in the literature with a stated preferences experiment of hybrid school leaders' perceptions of program success. Sixty-three school leaders participated in a survey experiment in which we randomly assigned attributes to hypothetical programs and asked school leaders to identify the most successful program. We find that hybrid school leaders consider a broad range of student outcomes when evaluating program success, including labor market outcomes, civic outcomes, and family life. Students' religious observance produced the largest effect sizes, a reasonable finding considering that roughly two-thirds of the schools represented in our sample have some religious affiliation. We do not find evidence that test score outcomes and higher education matriculation contribute meaningfully to perceived success.
Published: 2024

10. Federated learning enables big data for rare cancer boundary detection

Author: Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña Quintero, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S. Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela LaMontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard McKinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I. Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. van der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W. Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. van den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu’aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, and Spyridon Bakas
Subjects: Science
Abstract: Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.
Published: 2022
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11. Deep reinforcement learning-based beam training with energy and spectral efficiency maximisation for millimetre-wave channels

Author: Narengerile, John Thompson, Paul Patras, and Tharmalingam Ratnarajah
Subjects: 6G, Millimetre wave, Beam training, Deep reinforcement learning, Spectral efficiency, Energy efficiency, Telecommunication, TK5101-6720, Electronics, TK7800-8360
Abstract: Abstract The millimetre-wave (mmWave) spectrum has been investigated for the fifth generation wireless system to provide greater bandwidths and faster data rates. The use of mmWave signals allows large-scale antenna arrays to concentrate the radiated power into narrow beams for directional transmission. The beam alignment at mmWave frequency bands requires periodic training because mmWave channels are sensitive to user mobility and environmental changes. To benefit from machine learning technologies that will be used to build the sixth generation (6G) communication systems, we propose a new beam training algorithm via deep reinforcement learning. The proposed algorithm can switch between different beam training techniques according to the changes in the wireless channel such that the overall beam training overhead is minimised while achieving good performance of energy efficiency or spectral efficiency. Further, we develop a beam training strategy which can maximise either energy efficiency or spectral efficiency by controlling the number of activated radio frequency chains based on the current channel conditions. Simulation results show that compared to baseline algorithms, the proposed approach can achieve higher energy efficiency or spectral efficiency with lower training overhead.
Published: 2022
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12. Towards 6G: Spectrally efficient joint radar and communication with radio frequency selection, interference and hardware impairments (invited paper)

Author: Aryan Kaushik, Evangelos Vlachos, John Thompson, Maziar Nekovee, and Fraser Coutts
Subjects: 5G mobile communication, MIMO communication, MIMO radar, precoding, Telecommunication, TK5101-6720
Abstract: Abstract The joint radar‐communication (JRC) system is envisioned as an emerging sixth generation (6G) technology to tackle spectral congestion and hardware limitations by jointly implementing the communication and radar sensing on the same hardware platform and using the common radio frequency (RF) resources. Joint radar‐communication systems with a multi‐antenna setup leads to higher degrees of freedom, and hybrid beamforming can be exploited to achieve lower hardware complexity than conventional fully digital systems. This paper aims to design a spectral efficiency maximisation approach for a 6G inclined JRC system with hybrid beamforming and multi‐antenna setup while considering the interference between communication and radar operations and hardware impairments in the system. The rate expressions for communication and radar operations are defined, and the joint spectral efficiency is maximised via optimising the number of RF chains using an efficient selection algorithm taking into account the interference of one operation to the other and system hardware distortion. The simulation results are shown to support the effectiveness of the proposed approach, and they are compared with that of existing fully digital and hybrid beamforming based baseline methods with fixed number of RF chains. The proposed approach also exhibits a desirable communication‐radar trade‐off in terms of spectral efficiency gains.
Published: 2022
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13. Maternal Cardiovascular Responses to Position Change in Pregnancy

Author: Alys R. Clark, Hanna Fontinha, John Thompson, Sophie Couper, Devanshi Jani, Ali Mirjalili, Laura Bennet, and Peter Stone
Subjects: autonomic control, blood flow, cardiovascular adaptions, magnetic resonance imaging, pregnancy, Biology (General), QH301-705.5
Abstract: The maternal cardiovascular-circulatory system undergoes profound changes almost from the conception of a pregnancy until the postpartum period to support the maternal adaptions required for pregnancy and lactation. Maintenance of cardiovascular homeostasis requires changes in the cardiovascular autonomic responses. Here, we present a longitudinal study of the maternal cardiovascular autonomic responses to pregnancy and maternal position. Over a normal gestation, in the left lateral position there are significant changes in both time and frequency domain parameters reflecting heart rate variability. We show that cardiovascular autonomic responses to physiological stressors (standing and supine positions in late pregnancy) became significantly different with advancing gestation. In the third trimester, 60% of the subjects had an unstable heart rate response on standing, and these subjects had a significantly reduced sample entropy evident in their heart rate variability data. By 6 weeks, postpartum function returned to near the non-pregnant state, but there were consistent differences in high-frequency power when compared to nulligravid cases. Finally, we review complementary evidence, in particular from magnetic resonance imaging, that provides insights into the maternal and fetal impacts of positioning in pregnancy. This demonstrates a clear relationship between supine position and maternal hemodynamic parameters, which relates to compression of the inferior vena cava (p = 0.05). Together, these studies demonstrate new understanding of the physiology of physiological stressors related to position.
Published: 2023
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14. Comprehensive practical evaluation of wired and wireless internet base smart grid communication

Author: Mehdi Zeinali and John Thompson
Subjects: client-server systems, data compression, Internet, telecommunication computing, transport protocols, smart power grids, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: Abstract Internet‐based communications is a key solution for enabling low‐cost and scalable communication infrastructure for different applications of the smart grid. However, the performance of this network needs to be evaluated practically in the context of smart grid applications based on key metrics such as latency and reliability. This article is a comprehensive evaluation of the United Kingdom Internet network characteristics which will allow the smart grid systems designer to consider the essential parameters for communication applications. This article will focus not only on three smart grid applications, but also the outcome of this research which is relevant to a wider range of Internet of Things (IoT) applications. Different combinations of off‐the‐shelf wired and wireless last‐mile communication technologies are evaluated using real‐world transport protocols such as the Transport Control Protocol (TCP)and the User Datagram Protocol (UDP). The performance of TCP/UDP has been tested in a realistic client‐server communication test‐bed. The results from extensive evaluations show that typical latency values are between 200 and 600 ms for data packets and 50 bytes and kbytes for short control packets. Moreover by applying data compression techniques ,the results can be improved about 5%–20% for different last mile communications.
Published: 2021
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15. Cyberspace, Black-Hat Hacking and Economic Sustainability of Corporate Organizations in Cross-River State, Nigeria

Author: John Thompson Okpa, Christopher Uchechukwu Ugwuoke, Benjamin Okorie Ajah, Emmanuel Eshiotse, Joseph Egidi Igbe, Ogar James Ajor, Ofem, Nnana Okoi, Mary Juachi Eteng, and Rebecca Ginikanwa Nnamani
Subjects: History of scholarship and learning. The humanities, AZ20-999, Social Sciences
Abstract: Globally, e-commerce offers unlimited opportunities for corporate organizations to flourish as its customers reside in all parts of the universe. However, given the fluid nature of the cyberspace, black-hat hackers have enormously taken undue advantages of such mobility to perpetrate numerous financial frauds against individuals and corporate organizations. The impact of their attacks on the economic sustainability of corporate organizations is of obvious policy relevance, but little is empirically known about it. This study examined the role cyberspace plays in aiding the criminal activities of black-hat hackers and the impact of such malicious attacks on the economic sustainability of corporate organizations in Cross River State, Nigeria. An exploratory cross-sectional survey research design that allows the triangulation of quantitative and qualitative methods was adopted. Questionnaires were distributed to 1,074 respondents purposively selected from 18 financial institutions, 4 telecommunication network providers, and 2 manufacturing companies, while an in-depth interview was conducted on 13 participants across the selected corporate organizations. The presentation of data was done using frequency distribution tables, charts and relevant narratives. Chi-square was used to test the hypothesis, and content analyzing was adopted to analyze the qualitative data. The study found that corporate organizations with previous hacking experience are more likely to perceive black-hat hacking as affecting the productivity of their organization. The study, therefore, recommends that corporate organizations should strengthen their firewalls; educate their staff on the dangers of visiting unsafe websites, and downloading unverified attachments or clicking on links in unfamiliar emails.
Published: 2022
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16. Author Correction: Federated learning enables big data for rare cancer boundary detection

Author: Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S. Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela LaMontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard McKinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I. Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. van der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W. Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. van den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu’aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, and Spyridon Bakas
Subjects: Science
Published: 2023
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17. SOMAscan Proteomics Identifies Serum Biomarkers Associated With Liver Fibrosis in Patients With NASH

Author: Yi Luo, Samir Wadhawan, Alex Greenfield, Benjamin E. Decato, Abdul M. Oseini, Rebecca Collen, Diane E. Shevell, John Thompson, Gabor Jarai, Edgar D. Charles, and Arun J. Sanyal
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Nonalcoholic steatohepatitis (NASH) is a major cause of liver‐related morbidity and mortality worldwide. Liver fibrosis stage, a key component of NASH, has been linked to the risk of mortality and liver‐related clinical outcomes. Currently there are no validated noninvasive diagnostics that can differentiate between fibrosis stages in patients with NASH; many existing tests do not reflect underlying disease pathophysiology. Noninvasive biomarkers are needed to identify patients at high‐risk of NASH with advanced fibrosis. This was a retrospective study of patients with histologically proven NASH with fibrosis stages 0‐4. The SOMAscan proteomics platform was used to quantify 1,305 serum proteins in a discovery cohort (n = 113). In patients with advanced (stages 3‐4) versus early fibrosis (stages 0‐2), 97 proteins with diverse biological functions were differentially expressed. Next, fibrosis‐stage classification models were explored using a machine learning–based approach to prioritize the biomarkers for further evaluation. A four‐protein model differentiated patients with stage 0‐1 versus stage 2‐4 fibrosis (area under the receiver operating characteristic curve [AUROC] = 0.74), while a 12‐protein classifier differentiated advanced versus early fibrosis (AUROC = 0.83). Subsequently, the model’s performance was validated in two independent cohorts (n = 71 and n = 32) with similar results (AUROC = 0.74‐0.78). Our advanced fibrosis model performed similarly to or better than Fibrosis‐4 index, aspartate aminotransferase–to‐platelet ratio index, and nonalcoholic fatty liver disease (NAFLD) fibrosis score–based models for all three cohorts. Conclusion: A SOMAscan proteomics‐based exploratory classifier for advanced fibrosis, consisting of biomarkers that reflect the complexity of NASH pathophysiology, demonstrated similar performance in independent validation cohorts and performed similarly or better than Fibrosis‐4 index, aspartate aminotransferase–to‐platelet ratio index, and NAFLD fibrosis score. Further studies are warranted to evaluate the clinical utility of these biomarker panels in patients with NAFLD.
Published: 2021
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18. FMCW Radar With Enhanced Resolution and Processing Time by Beam Switching

Author: Pascual D. Hilario Re, Davide Comite, Symon K. Podilchak, Cristian A. Alistarh, George Goussetis, Mathini Sellathurai, John Thompson, and Jaesup Lee
Subjects: Automotive radar, multiple-input multiple-output (MIMO) radar, short-range radar (SRR), substrate-integrated waveguide (SIW), Butler matrix, Telecommunication, TK5101-6720
Abstract: We present the design of a novel K-band radar architecture for short-range target detection. Applications include direction finding systems and automotive radar. The developed system is compact and low cost and employs substrate-integrated-waveguide (SIW) antenna arrays and a $4\times 4$ Butler matrix (BM) beamformer. In particular, the proposed radar transmits a frequency modulated continuous-wave (FMCW) signal at 24 GHz, scanning the horizontal plane by switching the four input ports of the BM in time. Also, in conjunction with a new processing method for the received radar signals, the architecture is able to provide enhanced resolution at reduced computational burden and when compared to more standard single-input multiple-output (SIMO) and multiple-input multiple-output (MIMO) systems. The radar performance has also been measured in an anechoic chamber and results have been analyzed by illuminating and identifying test targets which are 2° apart, while also making comparisons to SIMO and MIMO FMCW radars. Moreover, the proposed radar architecture, by appropriate design, can also be scaled to operate at other microwave and millimeter-wave frequencies, while also providing a computationally efficient multi-channel radar signal processing platform.
Published: 2021
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19. Multi-Tier Variable Height UAV Networks: User Coverage and Throughput Optimization

Author: Muhammad Nafees, John Thompson, and Majid Safari
Subjects: Unmanned aerial vehicles (UAVs), signal-to-interference-plus-noise ratio (SINR), fractional frequency reuse (FFR), area spectral efficiency (ASE), reinforcement learning (RL), Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: Unmanned aerial vehicles (UAVs) are increasingly considered to act as base stations (BSs) for the future wireless networks. Some of the crucial UAV-assisted network design challenges are the network coverage, throughput, and energy efficiency. Therefore, fast, low-complexity, and efficient UAV placement and resource allocation strategies are imperative. This paper presents a novel variable height multi-UAV deployment strategy to exploit the 3D flexibility of UAVs as BSs. We propose a multi-tier variable height UAV-based network deployment and compare its performance with the state-of-the-art equal height deployment. Height optimization is performed to deliver energy efficiency and throughput maximization for each cell. The results show that our proposed method is more energy-efficient in a multi-cell UAV network than the most widely used height optimization method in the literature. In UAV networks, users at the cell edges can receive very poor signal-to-interference-plus-noise ratio (SINR) levels due to interfering UAVs. To cope with this problem, we adopt a fractional frequency reuse (FFR) scheme to compensate low SINR levels. We optimize the SINR threshold corresponding to each cell to maximize their spectral efficiency (SE), thereby improving the network’s area spectral efficiency (ASE). The numerical results show that the proposed deployments provide significant gains in coverage density, SINR coverage probability, rate coverage, and ASE compared to equal height benchmark scheme. As the number of UAVs increases, the number of tiers need to increase to preserve the rate coverage of the network. Moreover, the performance of the proposed variable height model is expected to converge to that of equal height cellular design for a large number of UAVs.
Published: 2021
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20. A tool to evaluate proportionality and necessity in the use of restrictive practices in forensic mental health settings: the DRILL tool (Dundrum restriction, intrusion and liberty ladders)

Author: Harry G. Kennedy, Ronan Mullaney, Paul McKenna, John Thompson, David Timmons, Pauline Gill, Owen P. O’Sullivan, Paul Braham, Dearbhla Duffy, Anthony Kearns, Sally Linehan, Damian Mohan, Stephen Monks, Lisa McLoughlin, Paul O’Connell, Conor O’Neill, Brenda Wright, Ken O’Reilly, and Mary Davoren
Subjects: Forensic psychiatry, Forensic, Violence, Seclusion, Restraint, Observational Study, Psychiatry, RC435-571
Abstract: Abstract Background Prevention of violence due to severe mental disorders in psychiatric hospitals may require intrusive, restrictive and coercive therapeutic practices. Research concerning appropriate use of such interventions is limited by lack of a system for description and measurement. We set out to devise and validate a tool for clinicians and secure hospitals to assess necessity and proportionality between imminent violence and restrictive practices including de-escalation, seclusion, restraint, forced medication and others. Methods In this retrospective observational cohort study, 28 patients on a 12 bed male admissions unit in a secure psychiatric hospital were assessed daily for six months. Data on adverse incidents were collected from case notes, incident registers and legal registers. Using the functional assessment sequence of antecedents, behaviours and consequences (A, B, C) we devised and applied a multivariate framework of structured professional assessment tools, common adverse incidents and preventive clinical interventions to develop a tool to analyse clinical practice. We validated by testing assumptions regarding the use of restrictive and intrusive practices in the prevention of violence in hospital. We aimed to provide a system for measuring contextual and individual factors contributing to adverse events and to assess whether the measured seriousness of threating and violent behaviours is proportionate to the degree of restrictive interventions used. General Estimating Equations tested preliminary models of contexts, decisions and pathways to interventions. Results A system for measuring adverse behaviours and restrictive, intrusive interventions for prevention had good internal consistency. Interventions were proportionate to seriousness of harmful behaviours. A ‘Pareto’ group of patients (5/28) were responsible for the majority (80%) of adverse events, outcomes and interventions. The seriousness of the precipitating events correlated with the degree of restrictions utilised to safely manage or treat such behaviours. Conclusion Observational scales can be used for restrictive, intrusive or coercive practices in psychiatry even though these involve interrelated complex sequences of interactions. The DRILL tool has been validated to assess the necessity and demonstrate proportionality of restrictive practices. This tool will be of benefit to services when reviewing practices internally, for mandatory external reviewing bodies and for future clinical research paradigms.
Published: 2020
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21. Allele-Selective Knockdown of MYH7 Using Antisense Oligonucleotides

Author: Brian R. Anderson, Marianne L. Jensen, Peter H. Hagedorn, Sean C. Little, Richard E. Olson, Ron Ammar, Bernadette Kienzle, John Thompson, Ivar McDonald, Stephen Mercer, Jonas Vikesaa, Bettina Nordbo, Larry Iben, Yang Cao, Joanne Natale, Greg Dalton-Kay, Angela Cacace, Bo R. Hansen, Maj Hedtjärn, Troels Koch, and Linda J. Bristow
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Hundreds of dominant-negative myosin mutations have been identified that lead to hypertrophic cardiomyopathy, and the biomechanical link between mutation and disease is heterogeneous across this patient population. To increase the therapeutic feasibility of treating this diverse genetic population, we investigated the ability of locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) to selectively knock down mutant myosin transcripts by targeting single-nucleotide polymorphisms (SNPs) that were found to be common in the myosin heavy chain 7 (MYH7) gene. We identified three SNPs in MYH7 and designed ASO libraries to selectively target either the reference or alternate MYH7 sequence. We identified ASOs that selectively knocked down either the reference or alternate allele at all three SNP regions. We also show allele-selective knockdown in a mouse model that was humanized on one allele. These results suggest that SNP-targeting ASOs are a promising therapeutic modality for treating cardiac pathology. Keywords: antisense oligonucleotides, myosin, cardiac hypertrophy, cardiomyopathy, nucleic acid, RNA degradation
Published: 2020
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22. Intelligent Signal Detection Under Spatially Correlated Noise

Author: Lei Wang, Jiang Xue, John Thompson, and Jia Yu
Subjects: Correlated noise, eigen-increment stopping rule, Gerschgorin disk estimator, principal component analysis, direction of arrival, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: Detecting the signal of the antenna array is a major problem in theoretical research and practical application. In this paper, several new methods are given for the number of signals detection at first, secondly, a new method called Principal Component Analysis of Signal Estimation (PCASE) will be introduced which can simultaneously detect the number of signals and the direction of arrival. In recent decades, the signal detection method based on the information theory criterion has been widely studied. The problem has been adequately solved under the assumption of uncorrelated white noise. However, considering the actual situation of wireless communication, the noise is spatially correlated or the noise information is unknown. In this case, traditional methods such as Akaike's information criteria (AIC), minimum descriptive length (MDL) and sparse and parameter approach (SPA) will often lead to a wrong estimation. Therefore, this paper introduces an improved eigenvalue correction method for the number of signals, and applies it to two new methods: the improved eigenvalue gradient method (Im-EGM) and the improved eigen-increment stop rule (Im-EISR), and studies a new estimation algorithm based on signal cancellation (SC). In addition, previous algorithms for estimating the direction of arrival (such as MUSIC, ESPRIT) require the number of known signals to estimate the direction of arrival. Therefore, this paper proposes a new method called PCASE, which can estimate the number of signals and the direction of arrival at the same time. This method combines the SPA and the Principal Component Analysis method (PCA) in machine learning. Compared with the existing methods, the accuracy of these new methods is verified by Monte Carlo simulation.
Published: 2020
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23. Behind Bars But Not Sentenced: The Role of Computerized Central Repository in Addressing Awaiting-Trial Problems in Ebonyi State, Nigeria

Author: Benjamin Okorie Ajah, Uzochukwu Chukwuka Chinweze, Ifeyinwa Angela Ajah, Dominic Chukwuemeka Onyejegbu, Aloysius C. Obiwulu, Emeka M. Onwuama, and John Thompson Okpa
Subjects: History of scholarship and learning. The humanities, AZ20-999, Social Sciences
Abstract: Quick dispensation of justice is necessary for every democratic society to succeed. It is encouraging to see studies, concerns and active agitations from people on the promotion of quick justice in Nigeria. Unfortunately, these studies and agitations have not yielded any concrete results. This article examines how a computerized central repository system can address awaiting-trial problems in Ebonyi State. Utilizing quantitative and qualitative approaches of research, a sample of 1,498 respondents were drawn from Ebonyi State. Purposive and multi-stage sampling techniques were used to reach the respondents. Questionnaires and in-depth interviews served as instruments for data collection. After the administration of instruments, data were sorted, coded, and analyzed using descriptive statistics, Chi-square, Pearson Product Moment Correlation Coefficient, and multiple linear regressions. Findings confirmed that while there is an uptick of awaiting-trial problems in Nigeria, there are no meaningful provisions to address it despite the fact that provisions exist within the Nigerian legal framework. Regression analysis revealed the Information and Computer Technology (ICT) method facilitates pretrial detention and brings it to quick conclusion as against the manual method. Based on the findings, the study calls for the creation of a computerized platform to automate all the Criminal Justice bureaucratic processes and make them faster through a centrally based computerized centrally repository system that is accessible to all agencies involved in Criminal Justice administration.
Published: 2022
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24. Antagonistic Activity of Lactic Acid Bacteria Against Pathogenic Vibrios and Their Potential Use as Probiotics in Shrimp (Penaeus vannamei) Culture

Author: John Thompson, Mark A. Weaver, Ingrid Lupatsch, Robin J. Shields, Sue Plummer, Christopher J. Coates, and Andrew F. Rowley
Subjects: aquaculture, shellfish health, disease, biofloc, competitive exclusion, Carnobacterium maltaromaticum, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract: Probiotic use in aquaculture settings can be an approach for disease control and dietary supplementation. We assessed the antagonistic effect of culture supernatants of lactic acid bacteria on the growth of known shrimp pathogens, Vibrio (Listonella) anguillarum, Vibrio alginolyticus, and V. harveyi, using a quantitative microplate bioassay. Supernatants from Lactobacillus curvatus subsp. curvatus, L. plantarum, and Pediococcus acidolactici significantly inhibited the growth of these vibrios. The active component(s) were heat stable (> 100°C) and resistant to freeze-thawing. Most of this inhibitory activity was brought about by the production of an acid pH; however, there was evidence for other factors playing a role. In the search for novel probiotic bacteria, an organism was isolated from the gastrointestinal tract of healthy whiteleg shrimp (Penaeus vannamei)—identified tentatively as Carnobacterium maltaromaticum. This isolate, however, had less potent vibriocidal activity than the lactic acid bacteria and reduced shrimp survival at a dose of 1 × 107 bacteria/shrimp. During a 28-day feeding trial, juvenile P. vannamei fed with L. plantarum supplemented diets showed no gross changes in growth parameters compared with the control. We suggest that lactic acid bacteria could be incorporated into biofloc formulations to purge the growth of pathogenic vibrios in pond settings, rather than being fed directly to shrimp.
Published: 2022
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25. The effects of electrical stunning on the nervous activity and physiological stress response of a commercially important decapod crustacean, the brown crab Cancer pagurus L.

Author: Douglas M Neil, Amaya Albalat, and John Thompson
Subjects: Medicine, Science
Abstract: Increasing attention is being paid to the welfare of decapod crustaceans. Legislation exists for their humane slaughter in several countries and this is being debated in others. Electrical stunning may have potential for humane slaughter of crustaceans in some circumstances, although scientific data on the effectiveness of electrical stunning when applied to various species are limited. Assessment criteria for effective stunning have so far been based mainly on behavioural assessments, but these do not always reflect neural insensibility. In this study direct recordings of neural activity, both centrally and peripherally, have been used to provide more direct measures of the state of sensibility. We have also examined whether electrical stunning acts as a physiological stressor, using measures of haemolymph L-lactate. Experiments were performed on a commercially important decapod species, the brown crab Cancer pagurus L. Spontaneous activity within the CNS was arrested by electrical stunning, which is an indication of loss of sensibility. There were also specific effects on the peripheral nervous system, with loss of responsiveness to sensory stimulation, rendering the animals unresponsive to external stimuli, and a failure of motor activation. All these effects were apparent immediately after a 10s stun, and persisted for as long as tested (4h) indicating that the animals were also killed by the procedure. No autotomy of limbs occurred. Haemolymph L-lactate was found to be no greater following electrical stunning than after handling and sampling alone, and both were significantly lower than values reached in a range of environmental and commercial situations. For all these reasons we find that electrical stunning may meet criteria for humane slaughter of C. pagurus.
Published: 2022
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26. Percutaneous Modified Lapidus Procedure with Early Weightbearing: Technique and Early Outcomes of the First 30 Cases

Author: Bryan Bean MD, Devin R. Mangold MD, Mostafa Abousayed MD, MSc, Michelle M. Coleman MD, PhD, John Thompson MD, and Gregory P. Guyton MD
Subjects: Orthopedic surgery, RD701-811
Abstract: Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Minimally invasive techniques (MIS) have focused on first metatarsal osteotomies in hallux valgus correction. Concurrently, new fixation methods allow early weightbearing protocols with the open Lapidus procedure, with nonunion rates comparable to those of more traditional protocols requiring nonweightbearing. We aimed to assess clinical and radiographic results of an MIS-modified Lapidus technique with axial nail fixation (Phantom Lapidus Intramedullary Nail: Paragon28, Englewood, CO USA) and early weightbearing. Methods: After institutional review board approval, the first 30 consecutive percutaneous MIS-modified Lapidus procedures by a single surgeon were retrospectively reviewed. Indications for surgery included moderate to severe hallux valgus deformity with or without first tarsometatarsal joint (TMT) instability, first TMT arthritis, adolescent bunion, and failed prior surgery. All patients initiated weightbearing within 12 days and returned to regular footwear by 6 weeks postoperatively. Patients had a minimum follow-up period of 3 months (average 8.3 months). The pre- and postoperative visual analog scale (VAS) pain scores, intra- and postoperative complications, and need for revision surgery were recorded. Pre- and postoperative radiographs were used to evaluate the hallux valgus angle (HVA), 1-2 intermetatarsal angle (IMA), and sesamoid station. Postoperative radiographs were evaluated for signs of hardware loosening and union of the first TMT arthrodesis site. A postoperative CT scan was obtained if nonunion was suspected. Results: Thirty consecutive percutaneous modified Lapidus procedures were performed in 28 patients. VAS scores improved from 4.1 preoperatively to 1.8 at final follow-up. The IMA decreased 8.3 degrees to an average of 5.9 degrees. The HVA decreased 19.2 degrees to 11.7 degrees. The medial column was shortened by 0.6%. There were no intraoperative complications. There were two reoperations, including one nonunion requiring revision first TMT fusion with autograft and one hallux valgus recurrence requiring a distal chevron osteotomy. There were no wound complications, surgical site infections, hardware complications, postoperative transfer metatarsalgia, or nerve-related problems. Conclusion: The current study provides clinical evidence that the intramedullary nail is a biomechanically stable construct evidenced by the high union rate, lack of hardware failure, and tolerance for early weightbearing. This percutaneous modified Lapidus technique may allow for a low rate of wound complications, accelerated rehabilitaion, and improved cosmesis.
Published: 2022
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27. Inter-Rater and Intra-Rater Reliability of the Lawrence and Botte Classification System of Fifth Metatarsal Base Fractures

Author: Michelle M. Coleman MD, PhD, Naudereh B. Noori MD, Mostafa Abousayed MD, MSc, Neeta Shenvi, Devin R. Mangold MD, Patrick M. Kennedy, Casey Kuripla MD, Walter C. Hembree MD, Niall A. Smyth MD, John Thompson MD, Stuart D. Miller MD, and Kirk Easley Gr
Subjects: Orthopedic surgery, RD701-811
Abstract: Category: Trauma; Midfoot/Forefoot Introduction/Purpose: Fractures of the proximal fifth metatarsal are common injuries with a unique history. Treatment of these fractures is controversial, in part due to confusion regarding the nomenclature of the fracture subtypes. The most commonly utilized classification system is the Lawrence and Botte classification, which separates fractures into zones 1, 2, and 3 based on their relationship to the tuberosity and the 4th-5th intermetatarsal articulation. The purpose of this study was to evaluate the inter-rater and intra-rater reliability of the Lawrence and Botte classification of fifth metatarsal base fractures. Methods: Thirty sets of x-rays representing an equal number of zone 1, zone 2 and zone 3 fractures of varying chronicity were sent to eleven fellowship trained orthopedic foot and ankle surgeons. Surgeons were asked to classify each fracture according to the Lawrence and Botte classification system (round 1). No review of the classification system or visual aids were provided. Two weeks later, the same set of x-rays were reordered and renumbered in a random fashion. The surgeons then re-classified each fracture in a blinded fashion under the same conditions (round 2). Inter-rater and intra-rater reliability was summarized using the kappa statistic. To determine the source of variability between the zones, additional analyses were performed to determine the kappa statistic for a) combined zone 1 and 2 fractures versus zone 3 fractures and b) combined zone 2 and 3 fractures versus zone 1 fractures. Results: The Lawrence and Botte classification demonstrated substantial overall inter-rater agreement for both rounds 1 and 2 (kappa = 0.66 and 0.65, respectively). Zone 1 fractures demonstrated the highest inter-rater reliability (kappa = 0.83 and 0.83). There was moderate agreement for zone 2 fractures (kappa = 0.51 and 0.50). There was substantial agreement for zone 3 fractures (kappa = 0.64 and 0.65). Dichotomous evaluation of the zone 1 vs. combined zones 2-3 boundary yielded excellent agreement (kappa = 0.83, 0.83). The combined zones 1-2 vs. zone 3 boundary yielded a much lower agreement (kappa = 0.66, 0.65). Intra-rater reliability varied by individual, with kappa values ranging from 0.60 to 0.90, corresponding to modest to almost perfect agreement. Conclusion: The Lawrence and Botte classification system has overall substantial inter-rater and intra-rater reliability, but assessment of the interface between zone 2 and zone 3 fractures is much less reliable than that between zone 1 and zone 2. Previous studies of isolated zone 1 fractures most likely contain a homogenous fracture cohort, while studies of zone 2 or zone 3 fractures are likely to include a mixture of fracture types. Future studies may utilize supplemental imaging or modify the classification to best determine treatment of these more distal fractures.
Published: 2022
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28. Risk Factors for Complications Associated with Minimally Invasive Medial Displacement Calcaneal Osteotomy

Author: Michelle M. Coleman MD, PhD, John Thompson MD, MSc, Bryan Bean MD, and Gregory P. Guyton MD
Subjects: Orthopedic surgery, RD701-811
Abstract: Category: Hindfoot Introduction/Purpose: Several minimally invasive medial displacement calcaneal osteotomy (MIS MDCO) techniques have been described utilizing differing methods for creating the osteotomy. However, there are few clinical reports of the safety profile and outcomes after percutaneous MDCO procedures. The purpose of this study was to describe short-term outcomes and complications associated with MIS MDCO for the correction of hindfoot valgus deformities. Methods: A retrospective study was conducted of all patients who underwent consecutive minimally invasive MDCO for the treatment of a hindfoot valgus deformity by a single fellowship-trained foot and ankle orthopaedic surgeon from September 2013 to August 2018. Demographic data, treatment data, and complications were recorded from the electronic medical record for the duration of the patient's follow-up. Univariate statistics were used to determine the relationship between complications and demographic/treatment variables. A p
Published: 2022
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29. Field Evaluation of UF Filtration Pretreatment Impact on RO Membrane Scaling

Author: Yakubu A. Jarma, John Thompson, Bilal M. Khan, and Yoram Cohen
Subjects: high scaling propensity water, RO feed pretreatment, RO, Hydraulic engineering, TC1-978, Water supply for domestic and industrial purposes, TD201-500
Abstract: Pretreatment of reverse osmosis (RO) feed water of high mineral scaling propensity was evaluated with respect to downstream RO membrane scaling, for two different feed pretreatment configurations. The pretreatment schemes included (i) media sand filtration, followed by a hydrocyclone (HC) and (ii) a hydrocyclone, microfilter, and a UF module, where both configurations included mesh screens for added protection. The first pretreatment configuration reduced the source water turbidity to ~0.5 NTU, while treatment that included UF feed yielded turbidity of <˜0.1 NTU; both pretreatment strategies provided feed water turbidity within the range recommended for RO desalination. Membrane scaling tests, with the pretreated water without antiscalant dosing, using a plate-and-frame RO unit and a membrane monitoring system, provided real-time membrane surface images that were quantified with respect to the progression of mineral scaling. RO desalting of source water pretreated with the first configuration revealed flux decline that was 75% greater and scale coverage (primarily gypsum) a factor of approximately eight higher relative to desalting of UF-treated source water. The results suggest that RO desalting of high mineral scaling propensity water can significantly benefit from added UF treatment to achieve feedwater turbidity to well below the typically recommended 0.5 NTU upper limit.
Published: 2023
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30. Backhaul-Aware User Association and Throughput Maximization in UAV-Aided Hybrid FSO/RF Network

Author: Muhammad Nafees, Shenjie Huang, John Thompson, and Majid Safari
Subjects: free space optics (FSO), matching game theory (GT), reinforcement learning (RL), unmanned aerial vehicle (UAV), Motor vehicles. Aeronautics. Astronautics, TL1-4050
Abstract: Free-space optical (FSO) communication is expected to play an indispensable role with high data rates and low system complexity in beyond fifth-generation (B5G) networks. However, infrequent adverse weather conditions can incapacitate its performance. The combination of FSO and radio frequency (RF) has emerged as an effective alternative for meeting the growing need for high data rates in wireless communication networks. Unmanned aerial vehicles (UAVs) are also anticipated to play an instrumental role in B5G networks due to their flexible movement and deployment. In this paper, a UAV-aided hybrid FSO/RF backhauling system using a matching game theory (GT) and reinforcement learning (RL) framework is investigated. We deploy a UAV to provide a user offloading service to an already existing ground base station (GBS), which is facing a reduced backhaul capacity due to weather attenuation (e.g., fog). It is considered that the GBS has a pre-installed FSO backhaul connection to a macro-base station (MBS). However, during adverse weather conditions, the FSO backhaul is severely affected, compromising the reliability of the FSO link. With the reduced FSO backhaul capacity, the GBS needs an additional backhaul link to support its backhaul data transmission to the destination MBS. As a result, instead of building an expensive permanent parallel RF link for the rare foggy situation, a UAV can be hired to serve a portion of the users, thereby reducing the GBS load. The users perform a matching game-based procedure to select the base station (BS) of their choice to maximize their utility. The UAV is deployed at an optimal altitude, and the bandwidth partition between the GBS and the UAV is optimized to maximize the system throughput using RL. Real weather data from the cities of Edinburgh and London in the U.K. are used to evaluate the performance of the system. The numerical results show the superiority and effectiveness of the proposed scheme compared to conventional methods.
Published: 2023
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31. Efficacy and safety of vedolizumab and infliximab treatment for immune-mediated diarrhea and colitis in patients with cancer: a two-center observational study

Author: Xuemei Wang, Jessica Harris, John Thompson, Elad Sharon, Yinghong Wang, Aline Charabaty, Marc S Ernstoff, Jennifer McQuade, Michel Obeid, Stephen Hanauer, Amishi Shah, Fangwen Zou, Isabella C Glitza Oliva, David Faleck, Anusha Thomas, Deepika Satish, and David M Richards
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2021
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32. Understanding the Quality of the 2020 Census is Essential

Author: John Thompson
Subjects: Electronic computers. Computer science, QA75.5-76.95
Published: 2021
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33. Radiodensity analysis of medial column superconstruct fixation sites in midfoot Charcot neuroarthropathy

Author: Dominick J. Casciato, DPM, Ryan Stone, DPM, John Thompson, DPM, Marissa Venero, DPM, Michael Chiu, DPM, Jonathan Blum, DPM, FACFAS, Ian Barron, DPM, FACFAS, and Christopher Hyer, DPM, MS, FACFAS
Subjects: Surgery, RD1-811
Abstract: Charcot neuroarthropathy (CN) is a highly destructive, pathologic process with devastating consequences to foot structure and viability. The use of intramedullary fixation ‘superconstructs’ allows for ‘re-bar’ support of compromised bone and allows for some dynamic fixation. This study examines radiodensity in Hounsfield units (HU) to compare bone quality of medial column fixation targets using computed tomography (CT) scans between patients with and without midfoot CN. A retrospective chart review identified control (non-diabetic, non-CN; n = 29) and midfoot CN (n = 21) groups. Patient demographics and medical history were collected. Two reviewers measured the mean HU of a circular region of interest centered on the first metatarsal head and the anterior, middle, and posterior thirds of the talar body. Radiodensity was compared between groups, and among talar locations, Eichenholtz stages and Brodsky types, with statistical significance set at p ≤ 0.05. Age and body mass index were not significantly different between groups. The CN group maintained greater mean HU than the control group at the metatarsal head (p
Published: 2021
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34. 407 Preliminary safety, pharmacokinetics/pharmacodynamics, and antitumor activity of XmAb20717, a PD-1 x CTLA-4 bispecific antibody, in patients with advanced solid tumors

Author: Adil Daud, Rom Leidner, Ezra Cohen, Matthew Reilley, Siwen Hu-Lieskovan, Raphael Clynes, Roger Cohen, John Thompson, Mark Stein, Alain Mita, Bartosz Chmielowski, Yana Najjar, Elaine Shum, R Donald Harvey, Catherine Fleener, Ying Ding, Sowmya Chollate, Hector Avina, Jolene Shorr, and Barbara Hickingbottom
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2020
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35. Surgical fixation compared with cast immobilisation for adults with a bicortical fracture of the scaphoid waist: the SWIFFT RCT

Author: Joseph Dias, Stephen Brealey, Liz Cook, Caroline Fairhurst, Sebastian Hinde, Paul Leighton, Surabhi Choudhary, Matthew Costa, Catherine Hewitt, Stephen Hodgson, Laura Jefferson, Kanagaratnam Jeyapalan, Ada Keding, Matthew Northgraves, Jared Palmer, Amar Rangan, Gerry Richardson, Nicholas Taub, Garry Tew, John Thompson, and David Torgerson
Subjects: scaphoid fracture, screw fixation, plaster cast, union, randomised controlled trial, Medical technology, R855-855.5
Abstract: Background: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. Immediate surgical fixation of this fracture has increased. Objective: To compare the clinical effectiveness and cost-effectiveness of surgical fixation with cast treatment and early fixation in adults with scaphoid waist fractures that fail to unite. Design: Multicentre, pragmatic, open-label, parallel two-arm randomised controlled trial with an economic evaluation and a nested qualitative study. Setting: Orthopaedic departments of 31 hospitals in England and Wales recruited from July 2013, with final follow-up in September 2017. Participants: Adults (aged ≥ 16 years) presenting within 2 weeks of injury with a clear, bicortical fracture of the scaphoid waist on plain radiographs. Interventions: Early surgical fixation using Conformité Européenne-marked headless compression screws. Below-elbow cast immobilisation for 6–10 weeks and urgent fixation of confirmed non-union. Main outcome measures: The primary outcome and end point was the Patient-Rated Wrist Evaluation total score at 52 weeks, with a clinically relevant difference of 6 points. Secondary outcomes included Patient-Rated Wrist Evaluation pain and function subscales, Short Form questionnaire 12-items, bone union, range of movement, grip strength, complications and return to work. Results: The mean age of 439 participants was 33 years; 363 participants were male (83%) and 269 participants had an undisplaced fracture (61%). The primary analysis was on 408 participants with valid Patient-Rated Wrist Evaluation outcome data for at least one post-randomisation time point (surgery, n = 203 of 219; cast, n = 205 of 220). There was no clinically relevant difference in the Patient-Rated Wrist Evaluation total score at 52 weeks: the mean score in the cast group was 14.0 (95% confidence interval 11.3 to 16.6) and in the surgery group was 11.9 (95% confidence interval 9.2 to 14.5), with an adjusted mean difference of –2.1 in favour of surgery (95% confidence interval –5.8 to 1.6; p = 0.27). The non-union rate was low (surgery group, n = 1; cast group, n = 4). Eight participants in the surgery group had a total of 11 reoperations and one participant in the cast group required a reoperation for non-union. The base-case economic analysis at 52 weeks found that surgery cost £1295 per patient more (95% confidence interval £1084 to £1504) than cast treatment. The base-case analysis of a lifetime-extrapolated model confirmed that the cast treatment pathway was more cost-effective. The nested qualitative study identified patients’ desire to have a ‘sense of recovering’, which surgeons should address at the outset. Limitation: There were 17 participants who had initial cast treatment and surgery for confirmed non-union, which in 14 cases was within 6 months from randomisation and in three cases was after 6 months. Three of the four participants in the cast group who had a non-union at 52 weeks were not offered surgery. Conclusions: Adult patients with an undisplaced or minimally displaced scaphoid waist fracture should have cast immobilisation and suspected non-unions immediately confirmed and urgently fixed. Patients should be followed up at 5 years to investigate the effect of partial union, degenerative arthritis, malunion and screw problems on their quality of life. Trial registration: Current Controlled Trials ISRCTN67901257. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 52. See the NIHR Journals Library website for further project information.
Published: 2020
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36. Experiences of a multi-ethnic population with obesity receiving dietary interventions and probiotics in pregnancy, from the Healthy Mums and Babies randomised trial

Author: Karaponi Okesene-Gafa, Lesley McCowan, Chris McKinlay, Deirdre Nielsen, Jess Wilson, Rennae Taylor, Clare Wall, John Thompson, Caroline Crowther, and Marcus Henning
Subjects: Public aspects of medicine, RA1-1270
Abstract: # Aim To evaluate multi-ethnic participants’ feedback from the Healthy Mums and Babies (HUMBA) trial. # Methods In conjunction with the HUMBA trial, a survey of dietary educational preferences (provided by community health workers (CHWs) and supported by text messages) or routine dietary advice with probiotic or placebo capsules was conducted in a multi-ethnic sample of pregnant women with obesity residing in an area of high deprivation in South Auckland, New Zealand (NZ). # Results Of 230 participants, median BMI was 38.6 kg/m^2^, 22% were Māori, 49% Pacific and 64% in highest deprivation quintile. Over 80% completed the survey. Participants reported overall-experience was positive (92%); capsules easy to take (80%); if probiotics improved health, they would recommend to a friend (97%). Participants in dietary intervention reported input by CHWs helped: change their food intake (70%); eat healthy (73%); set goals to change diet (62%); keep to recommended weight-gain (63%); and would recommend intervention to a friend (82%). Participants reported text messages: were read (93%); helped them eat healthy (65%); messages from baby was a good idea (79%) and would recommend to a friend (79%). Satisfaction with CHW was not related to weight-gain or birthweight. # Conclusions In this high needs’ population, feedback of participation in the HUMBA trial was very positive. The dietary intervention provided by CHWs was valued.
Published: 2020
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37. Future PM2.5 emissions from metal production to meet renewable energy demand

Author: Sagar D Rathod, Tami C Bond, Zbigniew Klimont, Jeffrey R Pierce, Natalie Mahowald, Chaitri Roy, John Thompson, Ryan P Scott, Karin Olson Hoal, and Peter Rafaj
Subjects: PM2.5, emissions, renewables, metals, critical minerals, energy transition, Environmental technology. Sanitary engineering, TD1-1066, Environmental sciences, GE1-350, Science, Physics, QC1-999
Abstract: A shift from fossil fuel to renewable energy is crucial in limiting global temperature increase to 2 °C above preindustrial levels. However, renewable energy technologies, solar photovoltaics, wind turbines, and electric vehicles are metal-intensive, and the mining and smelting processes to obtain the needed metals are emission-intensive. We estimate the future PM _2.5 emissions from mining and smelting to meet the metal demand of renewable energy technologies in two climate pathways to be 0.3–0.6 Tg yr ^−1 in the 2020–2050 period, which are projected to contribute 10%–30% of total anthropogenic primary PM _2.5 combustion emissions in many countries. The concentration of mineral reserves in a few regions means the impacts are also regionally concentrated. Rapid decarbonization could lead to a faster reduction of overall anthropogenic PM _2.5 emissions but also could create more unevenness in the distributions of emissions relative to where demand occurs. Options to reduce metal-related PM _2.5 emissions by over 90% exist and are well understood; introducing policy requiring their installation could avoid emission hotspots.
Published: 2022
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38. Establishing a National Community of Practice for Newborn Screening Follow-Up

Author: Erin Darby, John Thompson, Carol Johnson, Sikha Singh, and Jelili Ojodu
Subjects: newborn screening, follow-up, short-term follow-up, technical assistance, community of practice, Pediatrics, RJ1-570
Abstract: Newborn screening (NBS) follow-up programs in the United States are managed at the state level, leaving limited opportunities for collaboration across programs and coordinated resource sharing. The Newborn Screening Technical assistance and Evaluation Program (NewSTEPs), a program of the Association of Public Health Laboratories (APHL), has established a national community of practice for NBS follow-up by creating a network of follow-up staff and stakeholders through education and engagement opportunities. The activities of NewSTEPs in support of NBS follow-up have strengthened information dissemination, collaboration, data collection and technical assistance-driven mentorship across the national system.
Published: 2021
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39. Inflammatory Colitis after Treatment of Melanoma with Talimogene Laherparepvec (T-VEC)

Author: Jennifer Gardner, Teresa Hyun, Gideon Steinbach, and John Thompson
Subjects: colitis, immune-related adverse event, immunotherapy, melanoma, talimogene laherparepvec, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Immunologic diseases. Allergy, RC581-607
Abstract: Talimogene laherparepvec (T-VEC) is an intralesional oncolytic viral therapy for the treatment of recurrent, unresectable cutaneous, subcutaneous, and nodal melanoma. It is thought to work through direct tumor oncolysis and by eliciting a tumor-specific systemic immune response. Immune-related adverse events have been reported only rarely with this therapy. We report a case of culture-negative, biopsy-proven colitis following pathologic complete response of recurrent, and intransit cutaneous melanoma to T-VEC. To the best of our knowledge, this is the first report of immune-related colitis following T-VEC.
Published: 2018
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40. Priority questions for biodiversity conservation in the Mediterranean biome: Heterogeneous perspectives across continents and stakeholders

Author: Francisco Moreira, Nicky Allsopp, Karen J. Esler, Grant Wardell‐Johnson, Leonardo Ancillotto, Margarita Arianoutsou, Jeffrey Clary, Lluis Brotons, Miguel Clavero, Panayiotis G. Dimitrakopoulos, Raquel Fagoaga, Peggy Fiedler, Ana F. Filipe, Eliezer Frankenberg, Milena Holmgren, Pablo A. Marquet, Maria J. Martinez‐Harms, Adriano Martinoli, Ben P. Miller, Linda Olsvig‐Whittaker, Patricio Pliscoff, Phil Rundel, Danilo Russo, Jasper A. Slingsby, John Thompson, Angela Wardell‐Johnson, and Pedro Beja
Subjects: climate change, governance, policy, recommendations, research questions, stakeholder differences, Ecology, QH540-549.5, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract: Abstract The identification of research questions with high relevance for biodiversity conservation is an important step towards designing more effective policies and management actions, and to better allocate funding among alternative conservation options. However, the identification of priority questions may be influenced by regional differences in biodiversity threats and social contexts, and to variations in the perceptions and interests of different stakeholders. Here we describe the results of a prioritization exercise involving six types of stakeholders from the Mediterranean biome, which includes several biodiversity hotspots spread across five regions of the planet (Europe, Africa, North and South America, and Australia). We found great heterogeneity across regions and stakeholder types in the priority topics identified and disagreement among the priorities of research scientists and other stakeholders. However, governance, climate change, and public participation issues were key topics in most regions. We conclude that the identification of research priorities should be targeted in a way that integrates the spectrum of stakeholder interests, potential funding sources and regional needs, and that further development of interdisciplinary studies is required. The key questions identified here provide a basis to identify priorities for research funding aligned with biodiversity conservation needs in this biome.
Published: 2019
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41. Climate Smart Agriculture? Governing the Sustainable Development Goals in Sub-Saharan Africa

Author: Peter Newell, Olivia Taylor, Lars Otto Naess, John Thompson, Hussein Mahmoud, Patrick Ndaki, Raphael Rurangwa, and Amdissa Teshome
Subjects: climate change, agriculture, SDGs, governance, sub-Sahara Africa, Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456
Abstract: This paper examines the political economic and governance challenges faced by African governments in operationalizing Climate-Smart Agriculture (CSA) as part of their pursuit of the United Nations Sustainable Development Goals (SDGs). There is a need to enrich our understanding of the diverse contexts and ways in which governments will have to navigate and address the inevitable choices and conflicts, synergies and trade-offs that will characterize efforts to simultaneously implement these global goals. Here we seek to develop an account of why and how countries are managing the interrelationship between SDGs, particularly those associated with food security and climate action. We develop explanations for the diversity in approaches and provide an initial assessment of what the consequences are for policy and practice. The analysis is informed by the contrasting experiences of four Eastern African countries, Kenya, Tanzania, Ethiopia, and Rwanda, as they seek to build more “climate resilient” food and agricultural systems that are compatible with achieving the SDGs.
Published: 2019
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42. Transformative Pedagogy and Visual Literacy: Reframing Art and Design Student Perspectives on Sustainability with Illustrated Infographics

Author: Lisa Winstanley, Jesse John Thompson, and Sophia Huey Shan Tan
Abstract: This study explores the integration of key Transformative Learning Theory (TLT) principles into design education to foster Visual Literacy (VL) and promote awareness of environmental issues among undergraduate students. Through thematic analysis of 22 illustrated infographics, ideation sketches and supporting textual data created by art and design students, the study examines patterns and insights related to perspective transformation, critical reflection, and visual writing skills. Findings reveal pedagogical efficacy when prompting students to explore counter-narratives to the prevailing negative zeitgeist, resulting in perspective transformation and critical reflection of the design process. In turn, this perspective shift and critical reflection fostered the development of students' abilities to convey complex ideas visually, thus broadening their visual vocabulary to advocate for positive change. Three main categories were considered: Critical Reflection, Perspective Transformation, and Visual Writing Skills, and six sub-categories were identified: Implicit Reflection, Paradigm Shift, Alternative Narratives, Rhetorical Concepts, Intentional Visual-Verbal Communication, and Emotional Visual Language. Implications for scholars include insights into curriculum development and the promotion of ethical and sustainable design practices, while pragmatic applications for faculty offer actionable recommendations for enhancing teaching practices. The study underscores the importance of ethical considerations, diverse perspectives, and real-world applications in nurturing students' growth as innovative, ethical and sustainable designers.
Published: 2024
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43. Comparing Commute Distances between Hybrid and Conventional Schools

Author: Eric Wearne and John Thompson
Abstract: One schooling sector that had been growing before the pandemic, hybrid schools, in which students attend physical classes fewer than five days per week and are homeschooled on the other days, has seen recent continued growth. One factor that has not been explored is the commuting patterns families follow to use these schools. Whether families drive more miles to attend these part-time schools, or fewer, or neither, is the question this study seeks to address. In this manuscript, using individual student address data, we examine the commute distances made by students at four schools: two conventional, 5-day private schools, and two hybrid schools. We find that suburban hybrid school students do commute longer distances, but fewer total miles per week.
Published: 2024
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44. Age at puberty and risk of asthma: A Mendelian randomisation study.

Author: Cosetta Minelli, Diana A van der Plaat, Bénédicte Leynaert, Raquel Granell, Andre F S Amaral, Miguel Pereira, Osama Mahmoud, James Potts, Nuala A Sheehan, Jack Bowden, John Thompson, Debbie Jarvis, George Davey Smith, and John Henderson
Subjects: Medicine
Abstract: BackgroundObservational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males.Methods and findingsMR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10(-5)) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10(-4)), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking.ConclusionsThis large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide.
Published: 2018
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45. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Author: Christopher J. Ricketts, Aguirre A. De Cubas, Huihui Fan, Christof C. Smith, Martin Lang, Ed Reznik, Reanne Bowlby, Ewan A. Gibb, Rehan Akbani, Rameen Beroukhim, Donald P. Bottaro, Toni K. Choueiri, Richard A. Gibbs, Andrew K. Godwin, Scott Haake, A. Ari Hakimi, Elizabeth P. Henske, James J. Hsieh, Thai H. Ho, Rupa S. Kanchi, Bhavani Krishnan, David J. Kwaitkowski, Wembin Lui, Maria J. Merino, Gordon B. Mills, Jerome Myers, Michael L. Nickerson, Victor E. Reuter, Laura S. Schmidt, C. Simon Shelley, Hui Shen, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Benjamin G. Vincent, Cathy D. Vocke, David A. Wheeler, Lixing Yang, William T. Kim, A. Gordon Robertson, Paul T. Spellman, W. Kimryn Rathmell, W. Marston Linehan, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Toshinori Hinoue, Peter W. Laird, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, onathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr., Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, and Armaz Mariamidze
Subjects: Biology (General), QH301-705.5
Abstract: Summary: Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas
Published: 2018
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46. Driver Fusions and Their Implications in the Development and Treatment of Human Cancers

Author: Qingsong Gao, Wen-Wei Liang, Steven M. Foltz, Gnanavel Mutharasu, Reyka G. Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M. Reynolds, Matthew A. Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q. Sun, Ken Chen, Alexander J. Lazar, Ryan C. Fields, Michael C. Wendl, Brian A. Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr., Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, and Armaz Mariamidze
Subjects: Biology (General), QH301-705.5
Abstract: Summary: Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. : Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability. Keywords: fusion, cancer, RNA, translocation, gene fusions
Published: 2018
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47. Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Author: Joel Saltz, Rajarsi Gupta, Le Hou, Tahsin Kurc, Pankaj Singh, Vu Nguyen, Dimitris Samaras, Kenneth R. Shroyer, Tianhao Zhao, Rebecca Batiste, John Van Arnam, Ilya Shmulevich, Arvind U.K. Rao, Alexander J. Lazar, Ashish Sharma, Vésteinn Thorsson, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, onathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr., Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, and Armaz Mariamidze
Subjects: Biology (General), QH301-705.5
Abstract: Summary: Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment. : Tumor-infiltrating lymphocytes (TILs) were identified from standard pathology cancer images by a deep-learning-derived “computational stain” developed by Saltz et al. They processed 5,202 digital images from 13 cancer types. Resulting TIL maps were correlated with TCGA molecular data, relating TIL content to survival, tumor subtypes, and immune profiles. Keywords: digital pathology, immuno-oncology, machine learning, lymphocytes, tumor microenvironment, deep learning, tumor-infiltrating lymphocytes, artificial intelligence, bioinformatics, computer vision
Published: 2018
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48. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

Author: Xinxin Peng, Zhongyuan Chen, Farshad Farshidfar, Xiaoyan Xu, Philip L. Lorenzi, Yumeng Wang, Feixiong Cheng, Lin Tan, Kamalika Mojumdar, Di Du, Zhongqi Ge, Jun Li, George V. Thomas, Kivanc Birsoy, Lingxiang Liu, Huiwen Zhang, Zhongming Zhao, Calena Marchand, John N. Weinstein, Oliver F. Bathe, Han Liang, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr., Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, and Armaz Mariamidze
Subjects: Biology (General), QH301-705.5
Abstract: Summary: Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes—modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility. : Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators. Keywords: The Cancer Genome Atlas, tumor subtypes, prognostic markers, somatic drivers, master regulator, therapeutic targets, drug sensitivity, carbohydrate metabolism
Published: 2018
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49. Systematic Analysis of Splice-Site-Creating Mutations in Cancer

Author: Reyka G. Jayasinghe, Song Cao, Qingsong Gao, Michael C. Wendl, Nam Sy Vo, Sheila M. Reynolds, Yanyan Zhao, Héctor Climente-González, Shengjie Chai, Fang Wang, Rajees Varghese, Mo Huang, Wen-Wei Liang, Matthew A. Wyczalkowski, Sohini Sengupta, Zhi Li, Samuel H. Payne, David Fenyö, Jeffrey H. Miner, Matthew J. Walter, Benjamin Vincent, Eduardo Eyras, Ken Chen, Ilya Shmulevich, Feng Chen, Li Ding, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr., Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, and Armaz Mariamidze
Subjects: Biology (General), QH301-705.5
Abstract: Summary: For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. : Jayasinghe et al. identify nearly 2,000 splice-site-creating mutations (SCMs) from over 8,000 tumor samples across 33 cancer types. They provide a more accurate interpretation of previously mis-annotated mutations, highlighting the importance of integrating data types to understand the functional and the clinical implications of splicing mutations in human disease. Keywords: splicing, RNA, mutations of clinical relevance
Published: 2018
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50. Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

Author: Theo A. Knijnenburg, Linghua Wang, Michael T. Zimmermann, Nyasha Chambwe, Galen F. Gao, Andrew D. Cherniack, Huihui Fan, Hui Shen, Gregory P. Way, Casey S. Greene, Yuexin Liu, Rehan Akbani, Bin Feng, Lawrence A. Donehower, Chase Miller, Yang Shen, Mostafa Karimi, Haoran Chen, Pora Kim, Peilin Jia, Eve Shinbrot, Shaojun Zhang, Jianfang Liu, Hai Hu, Matthew H. Bailey, Christina Yau, Denise Wolf, Zhongming Zhao, John N. Weinstein, Lei Li, Li Ding, Gordon B. Mills, Peter W. Laird, David A. Wheeler, Ilya Shmulevich, Raymond J. Monnat, Jr., Yonghong Xiao, Chen Wang, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Michael Miller, Sheila Reynolds, Vesteinn Thorsson, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Toshinori Hinoue, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Min Wang, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr., Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, and Armaz Mariamidze
Subjects: Biology (General), QH301-705.5
Abstract: Summary: DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy. : Knijnenburg et al. present The Cancer Genome Atlas (TCGA) Pan-Cancer analysis of DNA damage repair (DDR) deficiency in cancer. They use integrative genomic and molecular analyses to identify frequent DDR alterations across 33 cancer types, correlate gene- and pathway-level alterations with genome-wide measures of genome instability and impaired function, and demonstrate the prognostic utility of DDR deficiency scores. Keywords: The Cancer Genome Atlas PanCanAtlas project, DNA damage repair, somatic mutations, somatic copy-number alterations, epigenetic silencing, DNA damage footprints, mutational signatures, integrative statistical analysis, protein structure analysis
Published: 2018
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