Medical Genetics Commons^™

Rescue Of Auditory Function By A Single Administration Of Aav-Tmprss3 Gene Therapy In Aged Mice Of Human Recessive Deafness Dfnb8, Wan Du, Volkan Ergin, Corena Loeb, Mingqian Huang, Stewart Silver, Ariel Miura Armstrong, Zaohua Huang, Channabasavaiah B. Gurumurthy, Hinrich Staecker, Xuezhong Liu, Zheng-Yi Chen

Journal Articles: Genetics, Cell Biology & Anatomy

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3^A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. …

Detecting Overlapping Gene Regions Using The U-Net Attention Mechanism, Samuel Lemma

All Graduate Theses, Dissertations, and Other Capstone Projects

The current issue of locating, diagnosing, and treating cancer and other diseases linked to specific target genes necessitates the creation of a reliable system for precisely identifying target genes that are initially extracted from a human chromosome. Current methodologies often suffer from overlapping gene regions in the target gene that occurs during the analysis process, which can have a substantial impact on the accuracy of the results. Our recommended approach, which was the appropriate model to apply for this particular problem, is set to enhance the analytical process by utilizing neural networks' U-Net with an attention mechanism. We were able …

An Initial Experience Of Completion Hemispherotomy Via Magnetic Resonance-Guided Laser Interstitial Therapy, Vijay M Ravindra, Lucia Ruggieri, Nisha Gadgil, Angela P Addison, Ilana Patino, David D Gonda, Jason Chu, Laura Whitehead, Anne Anderson, Gloria Diaz-Medina, Kimberly Houck, Akshat Katyayan, Laura Masters, Audrey Nath, Michael Quach, James John Riviello, Elaine Seto, Krystal Elizabeth Sully, Latanya Agurs, Sonali Sen, Maureen Handoko, Rohini Coorg, Irfan Ali, Daniel Ikeda, Howard Weiner, Daniel J Curry

Duncan NRI Faculty and Staff Publications

Introduction: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy.

Methods: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively.

Results: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two …

Copy Number Alterations Of Aggressive Pituitary Neuroendocrine Tumors, Grace Zhang

Scripps Senior Theses

Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.

Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.

Genetic markers, such as copy number variations …

Upregulation Of The Escrt Pathway And Multivesicular Bodies Accelerates Degradation Of Proteins Associated With Neurodegeneration, Ron Benyair, Sai Srinivas Panapakkam Giridharan, Pilar Rivero-Ríos, Junya Hasegawa, Emily Bristow, Eeva-Liisa Eskelinen, Merav D Shmueli, Vered Fishbain-Yoskovitz, Yifat Merbl, Lisa M Sharkey, Henry L Paulson, Phyllis I Hanson, Samarjit Patnaik, Ismael Al-Ramahi, Juan Botas, Juan Marugan, Lois S Weisman

Duncan NRI Faculty and Staff Publications

Many neurodegenerative diseases, including Huntington’s disease (HD) and Alzheimer’s disease (AD), occur due to an accumulation of aggregation-prone proteins, which results in neuronal death. Studies in animal and cell models show that reducing the levels of these proteins mitigates disease phenotypes. We previously reported a small molecule, NCT-504, which reduces cellular levels of mutant huntingtin (mHTT) in patient fibroblasts as well as mouse striatal and cortical neurons from an HdhQ111 mutant mouse. Here, we show that NCT-504 has a broader potential, and in addition reduces levels of Tau, a protein associated with Alzheimer’s disease, as well as other tauopathies. We …

Powerful, Scalable And Resource-Efficient Meta-Analysis Of Rare Variant Associations In Large Whole Genome Sequencing Studies, Xihao Li, Corbin Quick, Hufeng Zhou, Sheila M. Gaynor, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Harald H. H. Goring, Michael Mahaney, Juan M. Peralta

School of Medicine Publications

Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of …

Using Rna-Based Therapies To Target The Kidney In Cardiovascular Disease, Trecia C Palmer, Robert W Hunter

Faculty, Staff and Student Publications

RNA-based therapies are currently used for immunisation against infections and to treat metabolic diseases. They can modulate gene expression in immune cells and hepatocytes, but their use in other cell types has been limited by an inability to selectively target specific tissues. Potential solutions to this targeting problem involve packaging therapeutic RNA molecules into delivery vehicles that are preferentially delivered to cells of interest. In this review, we consider why the kidney is a desirable target for RNA-based therapies in cardiovascular disease and discuss how such therapy could be delivered. Because the kidney plays a central role in maintaining cardiovascular …

Gibbs Process Distinguishes Survival And Reveals Contact-Inhibition Genes In Glioblastoma Multiforme, Afrooz Jahedi, Gayatri Kumar, Lavanya Kannan, Tarjani Agarwal, Jason Huse, Krishna Bhat, Kasthuri Kannan

Faculty, Staff and Student Publications

Tumor growth is a spatiotemporal birth-and-death process with loss of heterotypic contact-inhibition of locomotion (CIL) of tumor cells promoting invasion and metastasis. Therefore, representing tumor cells as two-dimensional points, we can expect the tumor tissues in histology slides to reflect realizations of spatial birth-and-death process which can be mathematically modeled to reveal molecular mechanisms of CIL, provided the mathematics models the inhibitory interactions. Gibbs process as an inhibitory point process is a natural choice since it is an equilibrium process of the spatial birth-and-death process. That is if the tumor cells maintain homotypic contact inhibition, the spatial distributions of tumor …

Formation Of Vasculogenic Mimicry: Role Of Melanoma Differentiation Associated Gene-9 In Human Melanoma, Jinkal Shah

Theses and Dissertations

Malignant melanoma (MM) is the most aggressive skin cancer and the most frequent skin disorder in Caucasians. MM is associated with aggressive and progressive disease states, leading to major cancer-related morbidity and mortality. Recent investigations identify an alternative pathway -vasculogenic mimicry (VM), which is considered a cancer hallmark that can independently facilitate tumor neovascularization by the formation of fluid-conducting and vascular endothelial cells. MM cells undergoing VM can dedifferentiate into numerous cellular phenotypes and acquire endothelial-like features, resulting in the formation of the de novo matrix-rich vascular-like networks, such as plasma and red blood cells. The co-generation of endothelial cells, …

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …

Genetic Sequencing Of Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections In Fully Vaccinated Healthcare Workers, Sara Haddad, John Zurlo, Zi-Xuan Wang, Bonnie Richards, Nitika Badjatia, Dagan Coppock

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Introduction

Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several efforts have been made to prevent infection, culminating in the development of highly effective vaccines. However, as genetic variants of the virus have emerged, concerns have arisen regarding potential limitations of available vaccines.

Methods

In this article, we evaluated SARS-CoV-2 breakthrough infections among 520 healthcare workers in a 950-bed hospital from March 1, 2021, to October 31, 2021, and stratified them according to the type of vaccine received. We tested for associations between Alpha and Delta strains of SARS-CoV-2 and clinical characteristics.

Results

During the study period, …

Public Mental Health During And After The Sars-Cov-2 Pandemic: Opportunities For Intervention, Melissa M Karnaze, Brent M Kious, Lindsay Z Feuerman, Sarah Classen, Jill O Robinson, Cinnamon S Bloss, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Importance: During the pandemic, the number of United States adults reporting clinically significant symptoms of anxiety and depression sky-rocketed, up from 11% in 2020 to more than 40% in 2021. Our current mental healthcare system cannot adequately accommodate the current crisis; it is therefore important to identify opportunities for public mental health interventions.

Objective: Assess whether modifiable emotional factors may offer a point of intervention for the mental health crisis.

Design setting and participants: From January 13 to 15, 2022, adults living in the United States were recruited via Amazon Mechanical Turk to complete an anonymous survey.

Main outcomes and …

Enhancing Reciprocity, Equity And Quality Of Ethics Review For Multisite Research During Public Health Crises: The Experience Of The Covid-19 Clinical Research Coalition Ethics Working Group, Vasiliki Rahimzadeh, Jennyfer Ambe, Jantina De Vries

Center for Medical Ethics and Health Policy Staff Publications

In this paper we report findings from a commissioned report to the COVID-19 Clinical Research Coalition on approaches to streamline multinational REC review/approval during public health emergencies. As currently envisioned in the literature, a system of REC mutual recognition is theoretically possible based on shared procedural REC standards, but raises numerous concerns about perceived inequities and mistrust.

Renewed Calls For Abortion-Related Research In The Post-Roe Era, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

“Extremely Slow And Capricious”: A Qualitative Exploration Of Genetic Researcher Priorities In Selecting Shared Data Resources, M Grace Trinidad, Kerry A Ryan, Chris D Krenz, J Scott Roberts, Amy L Mcguire, Raymond De Vries, Brian J Zikmund-Fisher, Sharon Kardia, Erica Marsh, Jane Forman, Madison Kent, David Wilborn, Kayte Spector-Bagdady

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Genetic researchers' selection of a database can have scientific, regulatory, and ethical implications. It is important to understand what is driving database selection such that database stewards can be responsive to user needs while balancing the interests of communities in equitably benefiting from advances.

Methods: We conducted 23 semistructured interviews with US academic genetic researchers working with private, government, and collaboratory data stewards to explore factors that they consider when selecting a genetic database.

Results: Interviewees used existing databases to avoid burdens of primary data collection, which was described as expensive and time-consuming. They highlighted ease of access as …

2023 Canadian Surgery Forum: Sept. 20-23, 2023, Raphaëlle Brière, Marce Émond, Axel Benhamed, Pierre-Gilles Blanchard, Sébastien Drolet, Rogeh Habashi, Bahar Golbon, Jonas Shellenberger, Jesse Pasternak, Shaila Merchant, Jonas Shellenberger, Julie La, Monakshi Sawhney, Susan Brogly, Lina Cadili, Michael Horkoff, Scott Ainslie, Jeffrey Demetrick, Brian Chai, Kevin Wiseman, Hamish Hwang, Zainab Alhumoud, Amro Salem, Rebecca Lau, Katherine Aw, Carolyn Nessim, Nada Gawad, Kameela Alibhai, Chelsea Towaij, Danielle Doan, Isabelle Raîche, Rahim Valji, Simon Turner, Patricia Nicole Balmes, Hamish Hwang, S Morad Hameed, Jun Guang Kendric Tan, Ruwan Wijesuriya, Jun Guang Kendric Tan, Nicole Lee Chui Hew, Ruwan Wijesuriya, Matthew Lund, Jeffrey Hawel, Jamie Gregor, Ken Leslie, Tori Lenet, Daniel Mcisaac, Julie Hallet, Angela Jerath, Manoj Lalu, Stuart Nicholls, Justin Presseau, Alan Tinmouth, Michael Verret, Christopher Wherrett, Dean Fergusson, Guillaume Martel, Sahil Sharma, Tyler Mckechnie, Gaurav Talwar, Janhavi Patel, Luke Heimann, Aristithes Doumouras, Dennis Hong, Cagla Eskicioglu, Christine Wang, Michael Guo, Longlong Huang, Shaun Sun, Noelle Davis, Julian Wang, Samuel Skulsky, Lindsey Sikora, Isabelle Raîche, Hyo Jin Son, Denise Gee, David Gomez, James Jung, Rajajee Selvam, Nieve Seguin, Lisa Zhang, Ariane Lacaille-Ranger, Lindsey Sikora, Daniel Mcisaac, Husein Moloo, Alicia Follett, Holly, Michael Organ, David Pace, Saba Balvardi, Pepa Kaneva, Koorosh Semsar-Kazerooni, Carmen Mueller, Melina Vassiliou, Mohammed Al Mahroos, Julio F Fiore, Kevin Schwartzman, Liane Feldman, Michael Guo, Ahmer Karimuddin, Gui Ping Liu, Trafford Crump, Jason Sutherland, Kala Hickey, Erin M Bonisteel, Jurgienne Umali, Ibrahim Dogar, Geoffrey Warden, Darrell Boone, Alexander Mathieson, Michael Hogan, David Pace, Nieve Seguin, Husein Moloo, Yiran Li, Gordon Best, Rachel Leong, Sam Wiseman, Ahmed Amine Alaoui, Roy Hajjar, Evelyne Wassef, Danny Sebastien Metellus, François Dagbert, Rasmy Loungnarath, Richard Ratelle, Frank Schwenter, Éric Debroux, Ramses Wassef, Marianne Gagnon-Konamna, Alfons Pomp, Carole S Richard, Herawaty Sebajang, Ahmed Amine Alaoui, Roy Hajjar, François Dagbert, Rasmy Loungnarath, Herawaty Sebajang, Richard Ratelle, Frank Schwenter, Éric Debroux, Ramses Wassef, Marianne Gagnon-Konamna, Alfons Pomp, Manuela M Santos, Carole S Richard, Ge Shi, Regina Leung, Christina Lim, Sarah Knowles, Simran Parmar, Christine Wang, Estifanos Debru, Fardowsa Mohamed, Megan Anakin, Yung Lee, Yasith Samarasinghe, Jigish Khamar, Bradley Petrisor, Tyler Mckechnie, Cagla Eskicioglu, Ilun Yang, Hanaa N Mughal, Mumtaz Bhugio, Muhammed A Gok, Usman A Khan, Alisha R Fernandes, Richard Spence, Geoffrey Porter, C Marius Hoogerboord, Katerina Neumann, Michal Pillar, Michael Guo, Neraj Manhas, Adrienne Melck, Tania Kazi, Tyler Mckechnie, Ghazal Jessani, Luke Heimann, Yung Lee, Dennis Hong, Cagla Eskicioglu, Tyler Mckechnie, Léa Tessier, Vicki Archer, Lily Park, Dan Cohen, Sameer Parpia, Mohit Bhandari, Joanna Dionne, Cagla Eskicioglu, Sara Bolin, Rebecca Afford, Madeleine Armstrong, Ahmer Karimuddin, Regina Leung, Ge Shi, Christina Lim, Aaron Grant, Julie Ann Van Koughnett, Sarah Knowles, Elizabeth Clement, Claire Lange, Aishwi Roshan, Ahmer Karimuddin, Tracy Scott, Kara Nadeau, Jennifer Macmillan, Jaime Wilson, Madeleine Deschenes, Aruba Nurullah, Caitlin Cahill, Victoria H Chen, Keiko M Patterson, Sam M Wiseman, Betty Wen, Joshua Bhudial, Anise Barton, Jessica Lie, Chan Mi Park, Laiji Yang, Natalia Gouskova, Dae Hyun Kim, Rebecca Afford, Sara Bolin, Dunavan Morris-Janzen, Alastair Mclellan, Ahmer Karimuddin, Victoria Archer, Zacharie Cloutier, Annie Berg, Tyler Mckechnie, Wojtek Wiercioch, Cagla Eskicioglu, Joëlle Labonté, Pascale Bisson, André Bégin, Sonia Gabriela Cheng-Oviedo, Yves Collin, Alisha R Fernandes, Intekhab Hossain, James Ellsmere, Charbel El-Kefraoui, Uyen Do, Andrew Miller, Araz Kouyoumdjian, David Cui, Elahe Khorasani, Tara Landry, Alexandre Amar-Zifkin, Lawrence Lee, Liane Feldman, Julio Fiore, Tran Michelle Au, Mark Oppenheimer, Sarvesh Logsetty, Raghad Alshammari, Mohammad Alabri, Ahmer Karimuddin, Carl Brown, Manoj J Raval, Paul Terry Phang, Samantha Bird, Zarrukh Baig, Nawaf Abu-Omar, Dilip Gill, Soumiya Suresh, Nathan Ginther, Marta Karpinski, Amandeep Ghuman, Peter R A Malik, Kameela Alibhai, Taryn Zabolotniuk, Isabelle Raîche, Nada Gawad, Sarah Mashal, Nathalie Boulanger, Larry Watt, Tarek Razek, Paola Fata, Jeremy Grushka, Evan G Wong, Intekhab Hossain, Maxim Landry, Sarah Mackey, Nicholas Fairbridge, Alison Greene, Mark Borgoankar, Cullen Kim, Diana Decarvalho, David Pace, Robin Wigen, Emily Walser, Jacob Davidson, Michael Dorward, Leanne Muszynski, Celia Dann, Natashia Seemann, Jennifer Lam, Kaitlyn Harding, A J Lowik, Caroline Guinard, Sam Wiseman, Odelle Ma, Valentin Mocanu, Andrea Lin, Shahzeer Karmali, David Bigam, Kaitlyn Harding, Grant Greaves, Brent Parker, Vu Nguyen, Azim Ahmed, Belinda Yee, Joël Perren, Mathew Norman, Morgan Grey, Rafael Perini, Fahd Jowhari, Adrian Bak, Jeremy Drung, Laura Allen, Daniele Wiseman, Bradley Moffat, Jeremy K H Lee, Catherine Mcguire, Isabelle Raîche, Mihaela Tudorache, Nada Gawad, Lily J Park, Flavia K Borges, Rahima Nenshi, Michael Jacka, Diane Heels-Ansdell, Marko Simunovic, Jessica Bogach, Pablo E Serrano, Lehana Thabane, P J Devereaux, Sauleha Farooq, Erica Lester, Janice Kung, Nori Bradley, Gordon Best, San Ahn, Lisa Zhang, Nicole Prince, Olivia Cheng-Boivin, Nieve Seguin, Harry Wang, Liam Quartermain, Sherry Tan, Jennifer Shamess, Mathilde Simard, Humberto Vigil, Isabelle Raîche, Mary Hanna, Husein Moloo, Riordan Azam, Gary Ko, Mayanne Zhu, Yanuga Raveendran, Christine Lam, Janet Tang, Amrit Bajwa, Marina Englesakis, Emma Reel, Jordan Cleland, Laura Snell, Gianni Lorello, Tulin Cil, Hilalion San Ahn, Catherine Dube, Daniel Mcisaac, David Smith, Alexie Leclerc, Jennifer Shamess, Alaa Rostom, Natalia Calo, Kednapa Thavorn, Husein Moloo, Simon Laplante, Louis Liu, Nadia Khan, Allan Okrainec, Odelle Ma, Andrea Lin, Valentin Mocanu, Shahzeer Karmali, David Bigam, Gladys Bruyninx, Ilinca Georgescu, Vladislav Khokhotva, Gaurav Talwar, Sahil Sharma, Tyler Mckechnie, Shuling Yang, Jigish Khamar, Dennis Hong, Aristithes Doumouras, Cagla Eskicioglu, Karina Spoyalo, Thais Ayres Rebello, Gyan Chhipi-Shrestha, Kelly Mayson, Rehan Sadiq, Kasun Hewage, Andrea Macneill, Susan Muncner, Mo Yu Li, Igor Mihajlovic, Mark Dykstra, Ryan Snelgrove, Haili Wang, Christina Schweitzer, Sam M Wiseman, Ivneet Garcha, Uzair Jogiat, Vickie Baracos, Simon R Turner, Dean Eurich, Heather Filafilo, Armin Rouhi, Alexandre Bédard, Eric L R Bédard, Yogita S Patel, Jacob A Alaichi, John Agzarian, Wael C Hanna, Yogita S Patel, Jacob A Alaichi, Esther Provost, Bobby Shayegan, Anthony Adili, Wael C Hanna, Nikkita Mistry, Anthony A Gatti, Yogita S Patel, Forough Farrokhyar, Feng Xie, Wael C Hanna, Kerrie A Sullivan, Forough Farrokhyar, Yogita S Patel, Moishe Liberman, Simon R Turner, Anne V Gonzalez, Rahul Nayak, Kazuhiro Yasufuku, Wael C Hanna, Nikkita Mistry, Anthony A Gatti, Yogita S Patel, Sam Cross, Forough Farrokhyar, Feng Xie, Wael C Hanna, Pier-Luc Haché, Geraud Galvaing, Serge Simard, Jocelyn Grégoire, Jean Bussières, Yves Lacasse, Sami Sassi, Catherine Champagne, Anne-Sophie Laliberté, Jin Yong Jeong, Uzair Jogiat, Hillary Wilson, Alexandre Bédard, Pam Blakely, Jerry Dang, Warren Sun, Shahzeer Karmali, Eric L R Bédard, Clarence Wong, Suhail Yaqoob Hakim, Samim Azizi, Ayman El-Menyar, Sandro Rizoli, Hassan Al-Thani, Alisha R Fernandes, Daniel French, Chao Li, James Ellsmere, Shiloh Gossen, Daniel French, Jon Bailey, Phil Tibbo, Candice Crocker, Adom Bondzi-Simpson, Tiago Ribeiro, Biniam Kidane, Michael Ko, Natalie Coburn, Girish Kulkarni, Julie Hallet, Ahmed Faidh Ramzee, Ibrahim Afifi, Mushrek Alani, Ayman El-Menyar, Sandro Rizoli, Hassan Al-Thani, Talat Chughtai, Bright Huo, Daria Manos, Zhaolin Xu, Katerina-Maria Kontouli, Samuel Chun, John Fris, Allison M R Wallace, Daniel G French, Catherine Giffin, Moishe Liberman, Gabriel Dayan, Anne-Sophie Laliberté, Kazuhiro Yasufuku, Alexander Farivar, Biniam Kidane, Cara Weessies, Madeline Robinson, Leeann Bednarek, Gordon Buduhan, Richard Liu, Lawrence Tan, Sadeesh K Srinathan, Biniam Kidane, Awrad Nasralla, Najib Safieddine, Sayf Gazala, Carmine Simone, Negar Ahmadi, Roy Hilzenrat, Maurice Blitz, Shaun Deen, Michael Humer, Anand Jugnauth, Gordon Buduhan, Laura Kerr, Simon Sun, Ikennah Browne, Yogita Patel, Wael Hanna, Brandon Loshusan, Arefin Shamsil, Michael D Naish, Mehdi Qiabi, Rahul Nayak, Rajni Patel, Richard Malthaner, Patel Pooja, Ribeiro Roberto, Hirsch Greg, French Daniel, Caroline Huynh, Sohat Sharma, Arthur Vieira, Fagun Jain, Yejun Lee, Dorsa Mousa-Doust, Jonice Costa, Michelle Mezei, Kristine Chapman, Hannah Briemberg, Kristin Jack, Kyle Grant, James Choi, John Yee, Anna L Mcguire, Sami Aftab Abdul, Francois Khazoom, Katherine Aw, Rebecca Lau, Sebastien Gilbert, Sudhir Sundaresan, Daniel Jones, Andrew J E Seely, Patrick J Villeneuve, Donna E Maziak, Claudie-Anne Pigeon, Jonathan Frigault, Sébastien Drolet, Ève-Marie Roy, Kristopher Bujold-Pitre, Valérie Courval, Lea Tessier, Tyler Mckechnie, Yung Lee, Lily Park, Nirupa Gangam, Cagla Eskicioglu, Zacharie Cloutier, Tyler Mckechnie, Victoria Archer, Lily Park, Jay Lee, Ashaka Patel, Dennis Hong, Cagla Eskicioglu, Simarpreet Ichhpuniani, Tyler Mckechnie, Geoffrey Elder, Andrew Chen, Kathleen Logie, Aristithes Doumouras, Dennis Hong, Randy Benko, Cagla Eskicioglu, Matthew Castelo, Lawrence Paszat, Bettina Hansen, Adena Scheer, Neil Faught, Lena Nguyen, Nancy Baxter, Sahil Sharma, Tyler Mckechnie, Jigish Khamar, Kathy Wu, Cagla Eskicioglu, Tyler Mckechnie, Jigish Khamar, Yung Lee, Léa Tessier, Edward Passos, Aristithes Doumouras, Dennis Hong, Cagla Eskicioglu, Tyler Mckechnie, Jigish Khamar, Anjali Sachdeva, Yung Lee, Dennis Hong, Cagla Eskicioglu, Linda Y N Fei, Antonio Caycedo, Sunil Patel, Teodora Popa, Lee Boudreau, Andrea Grin, Tao Wang, Jessica Lie, Ahmer Karimuddin, Carl Brown, Terry Phang, Manoj Raval, Amandeep Ghuman, Sydney Candy, Kareena Nanda, Christine Li, Ryan Snelgrove, Mark Dykstra, Karen Kroeker, Haili Wang, Haven Roy, Ramzi M Helewa, Garrett Johnson, Harminder Singh, Eric Hyun, Dana Moffatt, Ashley Vergis, Patricia Balmes, Terry Phang, Michael Guo, Jerry Liu, Haven Roy, Sandra Webber, Farhana Shariff, Ramzi M Helewa, Dave Hochman, Jason Park, Garrett Johnson, Eric Hyun, Stephan Robitaille, Anna Wang, Michael Maalouf, Naser Alali, Hiba Elhaj, Sender Liberman, Patrick Charlebois, Barry Stein, Liane Feldman, Julio F Fiore, Lawrence Lee, Richard Hu, Ariane Lacaille-Ranger, San Ahn, Mihaela Tudorache, Husein Moloo, Lara Williams, Isabelle Raîche, Reilly Musselman, Maddy Lemke, Laura Allen, Nadeesha Samarasinghe, Kelly Vogt, Muriel Brackstone, Terry Zwiep, Elizabeth Clement, Claire Lange, Armaghan Alam, Anu Ghuman, Ahmer Karimuddin, Terry Phang, Manoj Raval, Carl Brown, Elizabeth Clement, Jerry Liu, Anu Ghuman, Ahmer Karimuddin, Terry Phang, Manoj Raval, Carl Brown, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Nicholas James, Terry Zwiep, Julie Ann Van Koughnett, Dora Laczko, Tyler Mckechnie, Shuling Yang, Kathy Wu, Sahil Sharma, Yung Lee, Lily Park, Aristithes Doumouras, Dennis Hong, Sameer Parpia, Mohit Bhandari, Cagla Eskicioglu, Tyler Mckechnie, Léa Tessier, Stephanie Lee, Tania Kazi, Praveen Sritharan, Yung Lee, Aristithes Doumouras, Dennis Hong, Cagla Eskicioglu, Tyler Mckechnie, Yung Lee, Dennis Hong, Joanna Dionne, Aristithes Doumouras, Sameer Parpia, Mohit Bhandari, Cagla Eskicioglu, Olivia Hershorn, Amandeep Ghuman, Ahmer Karimuddin, Carl Brown, Manoj Raval, P Terry Phang, Alex Chen, Marylise Boutros, Natasha Caminsky, Teodora Dumitra, Sarah Faris-Sabboobeh, Marie Demian, Georgia Rigas, Olivia Monton, Allister Smith, Jeongyoon Moon, Marie Demian, Richard Garfinkle, Carol-Ann Vasilevsky, Fateme Rajabiyazdi, Marylise Boutros, Emily Courage, Danielle Leblanc, Matthew Benesch, Kala Hickey, Katia Hartwig, Casey Armstrong, Reniel Engelbrecht, Mitchell Fagan, Mark Borgaonkar, David Pace, Jessica Shanahan, Jeongyoon Moon, Ebram Salama, Anna Wang, Mylène Arsenault, Nathalie Leon, Carmen Loiselle, Fatemeh Rajabiyazdi, Marylise Boutros, Kelly Brennan, Mandip Rai, Ameer Farooq, Chad Mcclintock, Weidong Kong, Sunil Patel, Neyla Boukhili, Natasha Caminsky, Sarah Faris-Sabboobeh, Marie Demian, Marylise Boutros, Tiffany Paradis, Stephan Robitaille, Teodora Dumitra, A Sender Liberman, Patrick Charlebois, Barry Stein, Julio F Fiore, Liane S Feldman, Lawrence Lee, Terry Zwiep, Deborah Abner, Tarik Alam, Elaine Beyer, Michele Evans, Mary Hill, Debra Johnston, Karla Lohnes, Svea Menard, Nicole Pitcher, Kelly Sair, Bev Smith, Bonita Yarjau, Kimberly Leblanc, Nadeesha Samarasinghe, Ahmer A Karimuddin, Carl J Brown, P Terry Phang, Manoj J Raval, Karen Macdonell, Amandeep Ghuman, Alexandra Harvey, P Terry Phang, Ahmer Karimuddin, Carl J Brown, Manoj J Raval, Amandeep Ghuman, Olivia Hershorn, Amandeep Ghuman, Ahmer Karimuddin, Manoj Raval, P Terry Phang, Carl Brown, Kathleen Logie, Tyler Mckechnie, Yung Lee, Dennis Hong, Cagla Eskicioglu, Mirna Matta, Laura Baker, Jessica Hopkins, Ryan Rochon, Donald Buie, Anthony Maclean, Amandeep Ghuman, Jason Park, Ahmer A Karimuddin, P Terry Phang, Manoj J Raval, Carl J Brown, Ameer Farooq, Amandeep Ghuman, Sunil Patel, Hugh Macdonald, Ahmer Karimuddin, Manoj Raval, P Terry Phang, Carl Brown, Vanessa Wiseman, Kelly Brennan, Sunil Patel, Ameer Farooq, Shaila Merchant, Weidong Kong, Chad Mcclintock, Chris Booth, Tim Hann, Alessandro Ricci, Sunil Patel, Kelly Brennan, Vanessa Wiseman, Chad Mcclintock, Weidong Kong, Ameer Farooq, Rohan Kakkar, Olivia Hershorn, Manoj Raval, P Terry Phang, Ahmer Karimuddin, Amandeep Ghuman, Carl Brown, Vanessa Wiseman, Ameer Farooq, Sunil Patel, Roy Hajjar, Emmanuel Gonzalez, Gabriela Fragoso, Manon Oliero, Ahmed Amine Alaoui, Hervé Vennin Rendos, Souad Djediai, Thibault Cuisiniere, Patrick Laplante, Claire Gerkins, Ayodeji Samuel Ajayi, Khoudia Diop, Nassima Taleb, Sophie Thérien, Frédéricke Schampaert, Hefzi Alratrout, François Dagbert, Rasmy Loungnarath, Herawaty Sebajang, Frank Schwenter, Ramses Wassef, Richard Ratelle, Éric Debroux, Jean-François Cailhier, Bertrand Routy, Borhane Annabi, Nicholas J B Brereton, Carole Richard, Manuela M Santos, Tamara Gimon, Helen Macrae, Anthony De Buck Van Overstraeten, Mantaj Brar, Sami Chadi, Erin Kennedy, Laura Baker, Jessica Hopkins, Ryan Rochon, Donald Buie, Anthony Maclean, Lily J Park, Victoria Archer, Tyler Mckechnie, Yung Lee, Daniel Mcisaac, Pavel Rashanov, Cagla Eskicioglu, Husein Moloo, P J Devereaux, Rehab Alsayari, Tyler Mckechnie, Simarpreet Ichhpuniani, Yung Lee, Cagla Eskicioglu, Roy Hajjar, Manon Oliero, Gabriela Fragoso, Ayodeji Samuel Ajayi, Ahmed Amine Alaoui, Hervé Vennin Rendos, Annie Calvé, Thibault Cuisinière, Claire Gerkins, Sophie Thérien, Nassima Taleb, François Dagbert, Herawaty Sebajang, Rasmy Loungnarath, Frank Schwenter, Richard Ratelle, Ramses Wassef, Eric Debroux, Carole Richard, Manuela M Santos, Erin Kennedy, Marko Simunovic, Selina Schmocker, Carl Brown, Anthony Maclean, Sender Liberman, Sébastien Drolet, Katerina Neumann, Peter Stotland, Kartik Jhaveri, Richard Kirsch, Hafssah Alnajem, Huseen Alibrahim, Christian Giundi, Alex Chen, Georgia Rigas, Haroon Munir, Ali Safar, Sarah Sabboobeh, Jessica Holland, Marylise Boutros, Erin Kennedy, Carole Richard, Marko Simunovic, Selina Schmocker, Carl Brown, Anthony Maclean, Sender Liberman, Sébastien Drolet, Katerina Neumann, Peter Stotland, Kartik Jhaveri, Richard Kirsch, Gladys Bruyninx, Dilip Gill, Rehab Alsayari, Tyler Mckechnie, Yung Lee, Dennis Hong, Cagla Eskicioglu, Lisa Zhang, Sean Abtahi, Allison Chhor, Gordon Best, Isabelle Raîche, Reilly Musselman, Lara Williams, Husein Moloo, Natasha Grace Caminsky, Jenny Jeongyoon Moon, Daniel Marinescu, Allison Pang, Carol-Ann Vasilevsky, Marylise Boutros, Mohammed Al-Abri, Elliott Gee, Ahmer Karimuddin, P Terry Phang, Carl Brown, Manoj Raval, Amandeep Ghuman, Nina Morena, Libby Ben-Zvi, Victoria Hayman, Mary Hou, Diana Nguyen, Carrie A Rentschler, Ari N Meguerditchian, Zuhaib Mir, Linda Fei, Sandra Mckeown, Rachelle Dinchong, Nicholas Cofie, Nancy Dalgarno, Rona Cheifetz, Shaila Merchant, Alisha Jaffer, Carolyn Cullinane, Gerard Feeney, Amirhossein Jalali, Anne Merrigan, Chwanrow Baban, Juliette Buckley, Shona Tormey, Matthew Benesch, Rongrong Wu, Kazuaki Takabe, Matthew Benesch, Shalana O'Brien, Karineh Kazazian, Ali Hosni Abdalaty, Christine Brezden, Ron Burkes, Eric Chen, Anand Govindarajan, Raymond Jang, Erin Kennedy, Jelena Lukovic, Aruz Mesci, Fayez Quereshy, Carol Swallow, Sami Chadi, Rogeh Habashi, Jesse Pasternak, Wanda Marini, Weiyue Zheng, Kiichi Murakami, Pamela Ohashi, Michael Reedijk, Richard Hu, Victoria Ivankovic, Lewis Han, Louise Gresham, Ranjeeta Mallick, Rebecca Auer, Tiago Ribeiro, Adom Bondzi-Simpson, Natalie Coburn, Julie Hallet, Tulin Cil, Adam Fontebasso, Alex Lee, Ericka Bernard-Bedard, Boaz Wong, Heidi Li, Elysia Grose, Olivier Brandts-Longtin, Katie Aw, Rebecca Lau, Ahmad Abed, James Stevenson, Rahat Sheikh, Richard Chen, Stephanie Johnson-Obaseki, Carolyn Nessim, Rachel Liu Hennessey, Adam T Meneghetti, Michael Bildersheim, Antoine Bouchard-Fortier, Gregg Nelson, Lloyd Mack, Farhad Ghasemi, Mahtab Malekian Naeini, Armen Parsyan, Yuvreet Kaur, Andrea Covelli, Fayez Quereshy, Elena Elimova, Elan Panov, Jelena Lukovic, James Brierley, Bev Burnett, Carol Swallow, Ashley Eom, David Kirkwood, Nicole Hodgson, Aristithes Doumouras, Jessica Bogach, Timothy Whelan, Mark Levine, Elena Parvez, Deanna Ng, Karineh Kazazian, Kiera Lee, Yi Qing Lu, Dae Kyum Kim, Marco Magalhaes, Emma Grigor, Angel Arnaout, Jing Zhang, Elliott K Yee, Julie Hallet, Nicole J Look Hong, Lena Nguyen, Natalie Coburn, Frances C Wright, Sonal Gandhi, Katarzyna J Jerzak, Andrea Eisen, Amanda Roberts, Daniel Ben Lustig, May Lynn Quan, Tien Phan, Antoine Bouchard-Fortier, Jeff Cao, Conrad Bayley, Akie Watanabe, Susan Yao, Eitan Prisman, Gary Groot, Elliot Mitmaker, Ross Walker, Jonn Wu, Jesse Pasternak, Chi Kien Lai, Antoine Eskander, Jonathan Wasserman, Frederic Mercier, Kathryn Roth, Sabrina Gill, Carlos Villamil, David Goldstein, Vicki Munro, Alok Pathak, Debon Lee, Anne Nguyen, Sam Wiseman, Luckshi Rajendran, Marco Claasen, Tommy Ivanics, Nazia Selzner, Ian Mcgilvray, Mark Cattral, Anand Ghanekar, Carol-Anne Moulton, Trevor Reichman, Chaya Shwaartz, Ur Metser, Ron Burkes, Erin Winter, Steven Gallinger, Gonzalo Sapisochin, Juan Glinka, Evelyn Waugh, Ken Leslie, Anton Skaro, Epharaim Tang, Juan Glinka, Janyssa Charbonneau, Alexandre Brind'amour, Alexis F Turgeon, Sarah O'Connor, Thomas Couture, Yifan Wang, Osamu Yoshino, Michael Driedger, Michael Beckman, Dionisios Vrochides, John Martinie, Abdulrahman Alabduljabbar, Maral Aali, Christopher Lightfoot, Boris Gala-Lopez, Maud Labelle, Frédérick D'Aragon, Yves Collin, Dhruvin Hirpara, Jonathan Irish, Mohammed Rashid, Tharsiya Martin, Alice Zhu, Leah Mcknight, Amber Hunter, Shiva Jayaraman, Alice Wei, Natalie Coburn, Frances Wright, Katlin Mallette, Ahmad Elnahas, Nawar Alkhamesi, Christopher Schlachta, Jeffrey Hawel, Ephraim Tang, Subin Punnen, Jade Zhong, Yuwei Yang, Lucas Streith, Jordan Yu, Stephen Chung, Peter Kim, Stephanie Chartier-Plante, Maja Segedi, Michael Bleszynski, Molly White, Melanie E Tsang, Shiva Jayaraman, Kimberley Lam-Tin-Cheung, Shiva Jayaraman, Melanie Tsang, Brittany Greene, Panthea Pouramin, Susan Allen, David Evan Nelson, Mark Walsh, Julien Côté, Rolando Rebolledo, Mélanie Borie, Ahmed Menaouar, Carolyne Landry, Marylène Plasse, Richard Létourneau, Michel Dagenais, Zhixia Rong, André Roy, Eve Beaudry-Simoneau, Franck Vandenbroucke-Menu, Réal Lapointe, Pasquale Ferraro, Shant Der Sarkissian, Nicolas Noiseux, Simon Turcotte, Yara Haddad, Antoine Bernard, Clara Lafortune, Nathalie Brassard, Annie Roy, Claude Perreault, Gaétan Mayer, Mieczyslaw Marcinkiewicz, Majambu Mbikay, Michel Chrétien, Simon Turcotte, Evelyn Waugh, Lynne Sinclair, Juan Glinka, Elizabeth Shin, Crystal Engelage, Ephraim Tang, Anton Skaro, Hala Muaddi, Jennifer Flemming, Bettina Hansen, Laura Dawson, Grainne O'Kane, Jordan Feld, Gonzalo Sapisochin, Alice Zhu, Shiva Jayaraman, Sean Cleary, Anthonie Hamel, Claudie-Anne Pigeon, Camille Marcoux, Thanh-Quan Philips Ngo, Isabelle Deshaies, Sarah Mansouri, Nawal Amhis, Maxime Léveillé, Christine Lawson, Carol Achard, Carolina Ilkow, Yves Collin, Lee-Hwa Tai, Lily Park, Christopher Griffiths, Daniel D'Souza, Felipe Rodriguez, Tyler Mckechnie, Pablo E Serrano, Rachel Liu Hennessey, Yuwei Yang, Adam T Meneghetti, O Neely M Panton, Chieh Jack Chiu, Oscar Henao, Fernando Spencer Netto, Marguerite Mainprize, Rachel Liu Hennessey, Chieh Jack Chiu, Rachel Liu Hennessey, Chieh Jack Chiu, Sukhdeep Jatana, Kevin Verhoeff, Valentin Mocanu, Uzair Jogiat, Daniel Birch, Shahzeer Karmali, Noah Switzer, Alexandra Hetherington, Kevin Verhoeff, Valentin Mocanu, Daniel Birch, Shahzeer Karmali, Noah Switzer, Ali Safar, Najla Al-Ghaithi, Phil Vourtzoumis, Sebastian Demyttenaere, Olivier Court, Amin Andalib, Hillary Wilson, Kevin Verhoeff, Jerry Dang, Janice Kung, Noah Switzer, Daniel Birch, Karen Madsen, Shahzeer Karmali, Valentin Mocanu, Ted Wu, Wenjing He, Ashley Vergis, Krista Hardy, Marta Zmudzinski, Felica Daenick, Janice Linton, Marta Zmudzinski, Melinda Fowler-Woods, Wenjing He, Amanda Fowler-Woods, Geraldine Shingoose, Ashley Vergis, Krista Hardy, Yung Lee, Aristithes Doumouras, Amber Molnar, Francis Nguyen, Dennis Hong, Romano Schneider, Andras B Fecso, Priya Sharma, Azusa Maeda, Timothy Jackson, Allan Okrainec, Cheynne Mclean, Valentin Mocanu, Daniel Birch, Shahzeer Karmali, Noah Switzer, Sarah Macvicar, Jerry Dang, Valentin Mocanu, Kevin Verhoeff, Uzair Jogiat, Shahzeer Karmali, Daniel Birch, Noah Switzer, Steffane Mclennan, Kevin Verhoeff, Kieran Purich, Jerry Dang, Janice Kung, Valentin Mocanu, Steffane Mclennan, Kevin Verhoeff, Valentin Mocanu, Uzair Jogiat, Daniel W Birch, Shahzeer Karmali, Noah J Switzer, Lisa Jeffery, Hamish Hwang, Alexis Ryley, Morgan Schellenberg, Natthida Owattanapanich, Brent Emigh, Chance Nichols, Joshua Dilday, Chaiss Ugarte, Atsushi Onogawa, Kazuhide Matsushima, Matthew J Martin, Kenji Inaba, Morgan Schellenberg, Brent Emigh, Chance Nichols, Joshua Dilday, Chaiss Ugarte, Atsushi Onogawa, Doug Shapiro, Daniel Im, Kenji Inaba, Morgan Schellenberg, Natthida Owattanapanich, Chaiss Ugarte, Lydia Lam, Matthew J Martin, Kenji Inaba, Joao Rezende-Neto, Sunil Patel, Lisa Zhang, Zuhaib Mir, Madeline Lemke, William Leeper, Laura Allen, Eric Walser, Kelly Vogt, Tiago Ribeiro, Sarah Bateni, Adom Bondzi-Simpson, Natalie Coburn, Julie Hallet, Victoria Barabash, Austin Barr, Wing Chan, Suhail Yaqoob Hakim, Ayman El-Menyar, Sandro Rizoli, Hassan Al-Thani, Hanaa N Mughal, Mumtaz Bhugio, Muhammed A Gok, Usman A Khan, Ahmed Warraich, Lawrence Gillman, Markus Ziesmann, Jovana Momic, Nouf Yassin, Mella Kim, Amy Makish, Eric Walser, Shane Smith, Ian Ball, Brad Moffat, Neil Parry, Kelly Vogt, Alex Lee, Jenna Kroeker, David Evans, Nahal Fansia, Chana Notik, Evan G Wong, Guire Coyle, David Seben, Jaiden Smith, Brandy Tanenbaum, Corey Freedman, Avery Nathens, Robert Fowler, Prachikumari Patel, Tim Elrick, Meghan Ewing, Steven Di Marco, Tarek Razek, Jeremy Grushka, Evan G Wong, Lily J Park, Flavia K Borges, Rahima Nenshi, Pablo E Serrano, Paul Engels, Kelly Vogt, Emily Di Sante, Jessica Vincent, Kate Tsiplova, P J Devereaux, Gaurav Talwar, Joanna Dionne, Tyler Mckechnie, Yung Lee, Tania Kazi, Abdullah El-Sayes, Jessica Bogach, Dennis Hong, Cagla Eskicioglu, Matthew Connell, Amanda Klooster, Jenna Beck, Kevin Verhoeff, Matt Strickland, Ram Anantha, Lilly Groszman, Natasha G Caminsky, Larry Watt, Nathalie Boulanger, Tarek Razek, Jeremy Grushka, Steven Di Marco, Evan G Wong, Rachel Livergant, Brooke Mcdonald, Catherine Binda, Shreya Luthra, Nicole Ebert, Ryan Falk, Emilie Joos

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Payer Reimbursement Practices And Incentives For Improving Interpretation Of Germline Genetic Testing, Patricia Deverka, Janis Geary, Charles Mathews, Matan Cohen, Gillian Hooker, Mary Majumder, Zuzana Skvarkova, Robert Cook-Deegan

Center for Medical Ethics and Health Policy Staff Publications

Germline genetic testing for inherited cancer risk has shifted to multi-gene panel tests (MGPTs). While MGPTs detect more pathogenic variants, they also detect more variants of uncertain significance (VUSs) that increase the possibility of harms such as unnecessary surgery. Data sharing by laboratories is critical to addressing the VUS problem. However, barriers to sharing and an absence of incentives have limited laboratory contributions to the ClinVar database. Payers can play a crucial role in the expansion of knowledge and effectiveness of genetic testing. Current policies affecting MGPT reimbursement are complex and create perverse incentives. Trends in utilization and coverage for …

Community Engagement In Precision Medicine Research: Organizational Practices And Their Impacts For Equity, Janet K Shim, Nicole Foti, Emily Vasquez, Stephanie M Fullerton, Michael Bentz, Melanie Jeske, Sandra Soo-Jin Lee

Center for Medical Ethics and Health Policy Staff Publications

Background: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal.

Methods: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for.

Results: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research. …

Payer Reimbursement Practices And Incentives For Improving Interpretation Of Germline Genetic Testing, Patricia Deverka, Janis Geary, Charles Mathews, Matan Cohen, Gillian Hooker, Mary Majumder, Zuzana Skvarkova, Robert Cook-Deegan

Center for Medical Ethics and Health Policy Staff Publications

Germline genetic testing for inherited cancer risk has shifted to multi-gene panel tests (MGPTs). While MGPTs detect more pathogenic variants, they also detect more variants of uncertain significance (VUSs) that increase the possibility of harms such as unnecessary surgery. Data sharing by laboratories is critical to addressing the VUS problem. However, barriers to sharing and an absence of incentives have limited laboratory contributions to the ClinVar database. Payers can play a crucial role in the expansion of knowledge and effectiveness of genetic testing. Current policies affecting MGPT reimbursement are complex and create perverse incentives. Trends in utilization and coverage for …

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M Willems, Natasha H J Ng, Juan Fernandez, Rebecca S Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Xueling Sim, Hanieh Yaghootkar, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Niels Grarup, Ruifang Li-Gao, Tibor V Varga, Jennifer L Asimit, Shuang Feng, Rona J Strawbridge, Erica L Kleinbrink, Tarunveer S Ahluwalia, Ping An, Emil V Appel, Dan E Arking, Juha Auvinen, Lawrence F Bielak, Nathan A Bihlmeyer, Jette Bork-Jensen, Jennifer A Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Anne U Jackson, Johanna Jakobsdottir, Marjo-Riitta Järvelin, Richard A Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Man Li, Yingchang Lu, Jian'an Luan, Alisa K Manning, Jonathan Marten, Karina Meidtner, Dennis O Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M Rice, Serena Sanna, Albert Vernon Smith, Jennifer A Smith, Lorraine Southam, Heather M Stringham, Vinicius Tragante, Sander W Van Der Laan, Helen R Warren, Jie Yao, Andrianos M Yiorkas, Weihua Zhang, Wei Zhao, Mariaelisa Graff, Heather M Highland, Anne E Justice, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W Asselbergs, Lori L Bonnycastle, Michiel L Bots, Ivan Brandslund, Ji Chen, John Danesh, Renée De Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, Epic-Interact Consortium, Aliki-Eleni Farmaki, Jessica D Faul, Paul W Franks, Steve Franks, Andreas Fritsche, Anette P Gjesing, Mark O Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B Harris, Karl-Heinz Herzig, Marie-France Hivert, Torben Jørgensen, Marit E Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L R Kardia, Leena Kinnunen, Heikki A Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A Lange, Lenore J Launer, Aaron Leong, Jaana Lindström, Jocelyn E Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A Nalls, Matthew Neville, James S Pankow, Alison Pattie, Eva R B Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D Taylor, Betina H Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group;, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P Bottinger, Mark J Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Francis S Collins, Josef Coresh, Francesco Cucca, Gert J De Borst, Ian J Deary, George Dedoussis, Panos Deloukas, Hester M Den Ruijter, Josée Dupuis, Michele K Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Torben Hansen, Andrew T Hattersley, Caroline Hayward, Joel N Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J F Loos, Patrick E Macdonald, Karen L Mohlke, Andrew D Morris, Patricia B Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A Peyser, Ozren Polasek, David Porteous, Michael A Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M Starr, Michael Stumvoll, Cornelia M Van Duijn, Mark Walker, Nick J Wareham, David R Weir, James G Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B Zonderman, Jerome I Rotter, Andrew P Morris, Michael Boehnke, Jose C Florez, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Robert A Scott, Anna L Gloyn, Inês Barroso

Faculty, Staff and Student Publications

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.

Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network …

Methodological Considerations In Pisces 3: A Randomized, Placebo-Controlled Study Of Intracerebral Stem Cells In Subjects With Disability Following An Ischemic Stroke, Daniel T Laskowitz, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Y Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, Laura Juel, Deborah Koltai, Brad J Kolls

Faculty, Staff and Student Publications

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6-12 months after an index ischemic stroke.

Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6-12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Cerebellar Dysfunction In Rodent Models With Dystonia, Tremor, And Ataxia, Meike E Van Der Heijden, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a movement disorder characterized by involuntary co- or over-contractions of the muscles, which results in abnormal postures and movements. These symptoms arise from the pathophysiology of a brain-wide dystonia network. There is mounting evidence suggesting that the cerebellum is a central node in this network. For example, manipulations that target the cerebellum cause dystonic symptoms in mice, and cerebellar neuromodulation reduces these symptoms. Although numerous findings provide insight into dystonia pathophysiology, they also raise further questions. Namely, how does cerebellar pathophysiology cause the diverse motor abnormalities in dystonia, tremor, and ataxia? Here, we describe recent work in rodents …

Function And Dysfunction Of The Dystonia Network: An Exploration Of Neural Circuits That Underlie The Acquired And Isolated Dystonias, Jason S Gill, Megan X Nguyen, Mariam Hull, Meike E Van Der Heijden, Ken Nguyen, Sruthi P Thomas, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a highly prevalent movement disorder that can manifest at any time across the lifespan. An increasing number of investigations have tied this disorder to dysfunction of a broad "dystonia network" encompassing the cerebellum, thalamus, basal ganglia, and cortex. However, pinpointing how dysfunction of the various anatomic components of the network produces the wide variety of dystonia presentations across etiologies remains a difficult problem. In this review, a discussion of functional network findings in non-mendelian etiologies of dystonia is undertaken. Initially acquired etiologies of dystonia and how lesion location leads to alterations in network function are explored, first through …

Social Behavioral Impairments In Syngap1-Related Intellectual Disability, Hajer Naveed, Maria Mccormack, J Lloyd Holder

Duncan NRI Faculty and Staff Publications

Introduction: Developmental synaptopathies are neurodevelopmental disorders caused by genetic mutations disrupting the development and function of neuronal synapses.

Methods: We administered the validated Social Responsiveness Scale, Second Edition (SRS-2) to investigate the phenotypic presentation of social-behavioral impairments for the developmental synaptopathy-SYNGAP1-related Intellectual Disability (SYNGAP1-ID) (n = 32) compared with a phenotypically similar disorder Phelan-McDermid syndrome (PMD) (n = 27) and healthy controls (n = 43). A short form SRS-2 analysis (n = 85) was also conducted.

Results: Both SYNGAP1-ID and PMD had significantly elevated total and subcategory T-scores, with no significant score differences between SYNGAP1 …

Examining Sociodemographic Correlates Of Opioid Use, Misuse, And Use Disorders In The All Of Us Research Program, Hsueh-Han Yeh, Cathryn Peltz-Rauchman, Christine C Johnson, Pamala A Pawloski, David Chesla, Stephen C Waring, Alan B Stevens, Mara Epstein, Christine Joseph, Lisa R Miller-Matero, Hongsheng Gui, Amy Tang, Eric Boerwinkle, Mine Cicek, Cheryl R Clark, Elizabeth Cohn, Kelly Gebo, Roxana Loperena, Kelsey Mayo, Stephen Mockrin, Lucila Ohno-Machado, Sheri Schully, Andrea H Ramirez, Jun Qian, Brian K Ahmedani

Faculty, Staff and Student Publications

Background: The All of Us Research Program enrolls diverse US participants which provide a unique opportunity to better understand the problem of opioid use. This study aims to estimate the prevalence of opioid use and its association with sociodemographic characteristics from survey data and electronic health record (EHR).

Methods: A total of 214,206 participants were included in this study who competed survey modules and shared EHR data. Adjusted logistic regressions were used to explore the associations between sociodemographic characteristics and opioid use.

Results: The lifetime prevalence of street opioids was 4%, and the nonmedical use of prescription opioids was 9%. …

Editorial: Advances In Mathematical And Computational Oncology, Volume Iii, George Bebis, Mamoru Kato, Mohammad Kohandel, Kathleen Wilkie, Dinler A Antunes, Ken Chen, Jinzhuang Dou

Faculty, Staff and Student Publications

No abstract provided.

Case Report: Responses To The Combination Of Gemcitabine With Sirolimus In Two Patients With Tsc-Mutated Sarcomas, Elise F Nassif, Cissimol P Joseph, Rossana Lazcano, Jocelyn T Joseph, Prapassorn Thirasastr, Alexander J Lazar, Neeta Somaiah

Faculty, Staff and Student Publications

TSC-mutated sarcomas are rare molecular and histologic types of sarcoma. Due to the presence of their specific oncogenic driver mutation, these sarcomas are particularly sensitive to mTOR inhibitors. Recently, nab-sirolimus, an albumin-bound mTOR inhibitor, was approved by the Food and Drug Administration (FDA) for PEComas, which harbor a TSC mutation, and this drug remains the only FDA-approved systemic treatment for these tumors. We report on two cases of patients with TSC-mutated sarcomas who experienced significant responses to the combination of gemcitabine and sirolimus, after progression on prior gemcitabine-based chemotherapy and single agent mTOR inhibition with nab-sirolimus. …

Stellettin B Sensitizes Glioblastoma To Dna-Damaging Treatments By Suppressing Pi3k-Mediated Homologous Recombination Repair, Xin Peng, Shaolu Zhang, Yingying Wang, Zhicheng Zhou, Zixiang Yu, Zhenxing Zhong, Liang Zhang, Zhe-Sheng Chen, Francois X Claret, Moshe Elkabets, Feng Wang, Fan Sun, Ran Wang, Han Liang, Hou-Wen Lin, Dexin Kong

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most aggressive type of cancer. Its current first-line postsurgery regimens are radiotherapy and temozolomide (TMZ) chemotherapy, both of which are DNA damage-inducing therapies but show very limited efficacy and a high risk of resistance. There is an urgent need to develop novel agents to sensitize GBM to DNA-damaging treatments. Here it is found that the triterpene compound stellettin B (STELB) greatly enhances the sensitivity of GBM to ionizing radiation and TMZ in vitro and in vivo. Mechanistically, STELB inhibits the expression of homologous recombination repair (HR) factors BRCA1/2 and RAD51 by promoting the degradation of PI3Kα …

Mass Spectrometry Based Biomarkers For Early Detection Of Hcc Using A Glycoproteomic Approach, Yehia Mechref, Wenjing Peng, Sakshi Gautam, Parisa Ahmadi, Yu Lin, Jianhui Zhu, Jie Zhang, Suyu Liu, Amit G Singal, Neehar D Parikh, David M Lubman

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide and 80%-90% of HCC develops in patients that have underlying cirrhosis. Better methods of surveillance are needed to increase early detection of HCC and the proportion of patients that can be offered curative therapies. Recent work in novel mass spec-based methods for glycomic and glycopeptide analysis for discovery and confirmation of markers for early detection of HCC versus cirrhosis is reviewed in this chapter. Results from recent work in these fields by several groups and the progress made in developing markers of early HCC which can outperform …