Medicine and Health Sciences Commons^™

Extrachromosomal Dna (Ecdna): An Origin Of Tumor Heterogeneity, Genomic Remodeling, And Drug Resistance., Lauren T Pecorino, Roel G W Verhaak, Anton Henssen, Paul S Mischel

Faculty Research 2022

The genome of cancer cells contains circular extrachromosomal DNA (ecDNA) elements not found in normal cells. Analysis of clinical samples reveal they are common in most cancers and their presence indicates poor prognosis. They often contain enhancers and driver oncogenes that are highly expressed. The circular ecDNA topology leads to an open chromatin conformation and generates new gene regulatory interactions, including with distal enhancers. The absence of centromeres leads to random distribution of ecDNAs during cell division and genes encoded on them are transmitted in a non-mendelian manner. ecDNA can integrate into and exit from chromosomal DNA. The numbers of …

An Fmri Protocol For Administering Liquid Incentives To Human Participants, Debbie M Yee, Jennifer L Crawford, Todd S Braver

2020-Current year OA Pubs

This protocol describes the materials and approaches for administering liquid incentives to human participants during fMRI scanning. We first describe preparation of the liquid solutions (e.g., neutral solution and saltwater) and liquid delivery setups. We then detail steps to connect the setups to the computer-controlled syringe pump in the MRI control room, followed by procedures for testing the syringe pump dispensing a liquid bolus during the task. Description of custom software and required adapters for implementing the liquid setup are included. For complete details on the use and execution of this protocol, please refer to Yee et al. (2021).

Mitochondrial Autophagy In Ischemic Aged Livers, Jae-Sung Kim, William C Chapman, Yiing Lin

2020-Current year OA Pubs

Mitochondrial autophagy (mitophagy) is a central catabolic event for mitochondrial quality control. Defective or insufficient mitophagy, thus, can result in mitochondrial dysfunction, and ultimately cell death. There is a strong causal relationship between ischemia/reperfusion (I/R) injury and mitochondrial dysfunction following liver resection and transplantation. Compared to young patients, elderly patients poorly tolerate I/R injury. Accumulation of abnormal mitochondria after I/R is more prominent in aged livers than in young counterparts. This review highlights how altered autophagy is mechanistically involved in age-dependent hypersensitivity to reperfusion injury.

A Whole-Genome Sequencing Study Implicates Gramd1b In Multiple Sclerosis Susceptibility, Federica Esposito, Bryan Bollman, Laura Piccio, Et Al.

2020-Current year OA Pubs

While the role of common genetic variants in multiple sclerosis (MS) has been elucidated in large genome-wide association studies, the contribution of rare variants to the disease remains unclear. Herein, a whole-genome sequencing study in four affected and four healthy relatives of a consanguineous Italian family identified a novel missense c.1801T > C (p.S601P) variant in the

Neuromotor Changes In Participants With A Concussion History Can Be Detected With A Custom Smartphone App, Christopher K. Rhea, Masahiro Yamada, Nikita A. Kuznetsov, Jason T. Jakiela, Chanel T. Lojacono, Scott E. Ross, F. J. Haran, Jason M. Bailie, W. Geoffrey Wright

Moss-Magee Rehabilitation Papers

Neuromotor dysfunction after a concussion is common, but balance tests used to assess neuromotor dysfunction are typically subjective. Current objective balance tests are either cost- or space-prohibitive, or utilize a static balance protocol, which may mask neuromotor dysfunction due to the simplicity of the task. To address this gap, our team developed an Android-based smartphone app (portable and cost-effective) that uses the sensors in the device (objective) to record movement profiles during a stepping-in-place task (dynamic movement). The purpose of this study was to examine the extent to which our custom smartphone app and protocol could discriminate neuromotor behavior between …

Adjuvant Nab-Paclitaxel + Gemcitabine In Resected Pancreatic Ductal Adenocarcinoma: Results From A Randomized, Open-Label, Phase Iii Trial, Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni

Department of Surgery Faculty Papers

PURPOSE

This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS

We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS

Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab …

Human Nk Cells Confer Protection Against Hiv-1 Infection In Humanized Mice, Can M. Sungur, Qiankun Wang, Ayşe N. Ozantürk, Hongbo Gao, Aaron J. Schmitz, Marina Cella, Wayne M. Yokoyama, Liang Shan

2020-Current year OA Pubs

The role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the humanized MISTRG-6-15 mouse model, in which NK cells were quick to expand and exhibit degranulation, cytotoxicity, and proinflammatory cytokine production in nonlymphoid organs upon HIV-1 infection but had reduced functionality in lymphoid organs. Although HIV-1 infection induced functional impairment of NK cells, antiretroviral therapy reinvigorated NK cells in response to HIV-1 rebound …

Social Attention During Object Engagement: Toward A Cross-Species Measure Of Preferential Social Orienting, Claire Weichselbaum, Nicole Hendrix, Jordan Albright, Joseph D Dougherty, Kelly N Botteron, John N Constantino, Natasha Marrus

2020-Current year OA Pubs

BACKGROUND: A central challenge in preclinical research investigating the biology of autism spectrum disorder (ASD) is the translation of ASD-related social phenotypes across humans and animal models. Social orienting, an observable, evolutionarily conserved behavior, represents a promising cross-species ASD phenotype given that disrupted social orienting is an early-emerging ASD feature with evidence for predicting familial recurrence. Here, we adapt a competing-stimulus social orienting task from domesticated dogs to naturalistic play behavior in human toddlers and test whether this approach indexes decreased social orienting in ASD.

METHODS: Play behavior was coded from the Autism Diagnostic Observation Schedule (ADOS) in two samples …

Topics And Sentiment Surrounding Vaping On Twitter And Reddit During The 2019 E-Cigarette And Vaping Use-Associated Lung Injury Outbreak: Comparative Study, Dezhi Wu, Erin Kasson, Avineet Kumar Singh, Yang Ren, Nina Kaiser, Ming Huang, Patricia A Cavazos-Rehg

2020-Current year OA Pubs

BACKGROUND: Vaping or e-cigarette use has become dramatically more popular in the United States in recent years. e-Cigarette and vaping use-associated lung injury (EVALI) cases caused an increase in hospitalizations and deaths in 2019, and many instances were later linked to unregulated products. Previous literature has leveraged social media data for surveillance of health topics. Individuals are willing to share mental health experiences and other personal stories on social media platforms where they feel a sense of community, reduced stigma, and empowerment.

OBJECTIVE: This study aimed to compare vaping-related content on 2 popular social media platforms (ie, Twitter and Reddit) …

Recurrent Switch 2 Domain Rac2 Mutations In Intravascular Large B-Cell Lymphoma, Rohan Kodgule, Jie Chen, Pooja Khonde, Joshua Robinson, Amy D'Albora, Lisa Cook, Catrina C Fronick, Robert Fulton, Sridhar Nonavinkere Srivatsan, Patrick J Cimino, Eric J Duncavage

2020-Current year OA Pubs

No abstract provided.

Tissue Registration And Exploration User Interfaces In Support Of A Human Reference Atlas, Katy Börner, Andreas Bueckle, Bruce W Herr 2nd, Leonard E Cross, Ellen M Quardokus, Elizabeth G Record, Yingnan Ju, Jonathan C Silverstein, Kristen M Browne, Sanjay Jain, Clive H Wasserfall, Marda L Jorgensen, Jeffrey M Spraggins, N Heath Patterson, Griffin M Weber

2020-Current year OA Pubs

Seventeen international consortia are collaborating on a human reference atlas (HRA), a comprehensive, high-resolution, three-dimensional atlas of all the cells in the healthy human body. Laboratories around the world are collecting tissue specimens from donors varying in sex, age, ethnicity, and body mass index. However, harmonizing tissue data across 25 organs and more than 15 bulk and spatial single-cell assay types poses challenges. Here, we present software tools and user interfaces developed to spatially and semantically annotate ("register") and explore the tissue data and the evolving HRA. A key part of these tools is a common coordinate framework, providing standard …

Molecular Classification And Biomarkers Of Clinical Outcome In Breast Ductal Carcinoma In Situ: Analysis Of Tbcrc 038 And Rahbt Cohorts, Siri H Strand, Deborah J Veis, Katherine Deschryver, Jen Tappenden, Jingqin Luo, Shu Jiang, Graham A Colditz, Et Al.

2020-Current year OA Pubs

Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression …

Mendelian Randomization And Genetic Colocalization Infer The Effects Of The Multi-Tissue Proteome On 211 Complex Disease-Related Phenotypes, Chengran Yang, Anne M Fagan, Richard J Perrin, Herve Rhinn, Oscar Harari, Carlos Cruchaga

2020-Current year OA Pubs

BACKGROUND: Human proteins are widely used as drug targets. Integration of large-scale protein-level genome-wide association studies (GWAS) and disease-related GWAS has thus connected genetic variation to disease mechanisms via protein. Previous proteome-by-phenome-wide Mendelian randomization (MR) studies have been mainly focused on plasma proteomes. Previous MR studies using the brain proteome only reported protein effects on a set of pre-selected tissue-specific diseases. No studies, however, have used high-throughput proteomics from multiple tissues to perform MR on hundreds of phenotypes.

METHODS: Here, we performed MR and colocalization analysis using multi-tissue (cerebrospinal fluid (CSF), plasma, and brain from pre- and post-meta-analysis of several …

Two-Year Follow-Up Of Kte-X19 In Patients With Relapsed Or Refractory Adult B-Cell Acute Lymphoblastic Leukemia In Zuma-3 And Its Contextualization With Scholar-3, An External Historical Control Study, Bijal D Shah, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care.

METHODS: Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 10

RESULTS: After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients (N = 55) in phase 2 was 71% …

Defective Proteostasis In Induced Pluripotent Stem Cell Models Of Frontotemporal Lobar Degeneration, Sidhartha Mahali, Rita Martinez, Melvin King, Anthony Verbeck, Oscar Harari, Bruno A Benitez, Kanta Horie, Chihiro Sato, Sally Temple, Celeste M Karch

2020-Current year OA Pubs

Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We …

Associations Of Aspirin And Other Anti-Inflammatory Medications With Breast Cancer Risk By The Status Of Cox-2 Expression, Lusine Yaghjyan, A Heather Eliassen, Graham Colditz, Bernard Rosner, Pepper Schedin, Akemi Wijayabahu, Rulla M Tamimi

2020-Current year OA Pubs

BACKGROUND: We investigated the associations of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with breast cancer risk by the status of COX-2 protein expression.

METHODS: This study included 421 cases and 3,166 controls from a nested case-control study within the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) cohorts. Information on medication use was first collected in 1980 (NHS) and 1989 (NHSII) and was updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users using data collected from all biannual questionnaires preceding the reference …

Safety Of Lenadogene Nolparvovec Gene Therapy Over 5 Years In 189 Patients With Leber Hereditary Optic Neuropathy, Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, José-Alain Sahel

Wills Eye Hospital Papers

Purpose

To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy.

Design

Pooled analysis of safety data from 5 clinical studies.

Methods

A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2.

Results

Almost all patients (95.2%) received 9 × …

Methylprednisolone For Heart Surgery In Infants - A Randomized, Controlled Trial, Kevin D Hill, Pirooz Eghtesady, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown.

METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes.

RESULTS: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for …

Prevalence Estimates Of Trafficking In Persons Using Statistical Definitions: A Cross-Sectional High-Risk Community Survey In Cape Town, South Africa, Rumi Kato Price, Annah K Bender, Floriana H Milazzo, Edna G Rich, Nicolette V Roman, Sheldon X Zhang, Erica L Koegler

2020-Current year OA Pubs

OBJECTIVES: Current research on trafficking in persons (TIP) relies heavily on legal and prosecutorial definitions. A public health approach has called for population-level assessment; however, identification of TIP victims lacks a standardised operational definition. This study applied the Prevalence Reduction Innovation Forum (PRIF) statistical definitions, developed by the US Department of State, to a community survey in Cape Town, South Africa.

DESIGNS: A high-risk sampling strategy was used. TIP screening questions from two instruments were matched with PRIF domain indicators to generate prevalence estimates. Sensitivity, specificity and receiver operating characteristics analyses were conducted to assess the performance of the two …

The Subcortical And Neurochemical Organization Of The Ventral And Dorsal Attention Networks, Pedro Nascimento Alves, Stephanie J Forkel, Maurizio Corbetta, Michel Thiebaut De Schotten

2020-Current year OA Pubs

Attention is a core cognitive function that filters and selects behaviourally relevant information in the environment. The cortical mapping of attentional systems identified two segregated networks that mediate stimulus-driven and goal-driven processes, the Ventral and the Dorsal Attention Networks (VAN, DAN). Deep brain electrophysiological recordings, behavioral data from phylogenetic distant species, and observations from human brain pathologies challenge purely corticocentric models. Here, we used advanced methods of functional alignment applied to resting-state functional connectivity analyses to map the subcortical architecture of the Ventral and Dorsal Attention Networks. Our investigations revealed the involvement of the pulvinar, the superior colliculi, the head …

Genetic Diversity Fuels Gene Discovery For Tobacco And Alcohol Use, Gretchen R B Saunders, Charles C Gu, John P Rice, Nancy L Saccone, Laura J Bierut, Et Al.

2020-Current year OA Pubs

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury

Evaluating Public Participation In A Deliberative Dialogue: A Single Case Study., Tiffany Scurr, Rebecca Ganann, Shannon L Sibbald, Ruta Valaitis, Anita Kothari

Health Studies Publications

BACKGROUND: Deliberative dialogues (DDs) are used in policy-making and healthcare research to enhance knowledge exchange and research implementation strategies. They allow organized dissemination and integration of relevant research, contextual considerations, and input from diverse stakeholder perspectives. Despite recent interest in involving patient and public perspectives in the design and development of healthcare services, DDs typically involve only professional stakeholders. A DD took place in May 2019 that aimed to improve the social environment (eg, safety, social inclusion) and decrease social isolation in a rent-geared-to-income housing complex in a large urban community. Tenants of the housing complex, public health, primary care, …

In Silico Identification Of A Β2-Adrenoceptor Allosteric Site That Selectively Augments Canonical Β2ar-Gs Signaling And Function, Sushrut D Shah, Christoffer Lind, Francesco De Pascali, Raymond B Penn, Alexander D Mackerell, Deepak A Deshpande

Department of Biochemistry and Molecular Biology Faculty Papers

Activation of β2-adrenoceptors (β2ARs) causes airway smooth muscle (ASM) relaxation and bronchodilation, and β2AR agonists (β-agonists) are front-line treatments for asthma and other obstructive lung diseases. However, the therapeutic efficacy of β-agonists is limited by agonist-induced β2AR desensitization and noncanonical β2AR signaling involving β-arrestin that is shown to promote asthma pathophysiology. Accordingly, we undertook the identification of an allosteric site on β2AR that could modulate the activity of β-agonists to overcome these limitations. We employed the site identification by ligand competitive saturation (SILCS) computational method to comprehensively map the entire 3D structure of in silico-generated β2AR intermediate conformations and identified …

Efficacy And Safety Of Pacritinib Vs Placebo For Patients With Severe Covid-19: A Phase 2 Randomized Clinical Trial, John Cafardi, Carole Miller, Howard Terebelo, Chad Tewell, Sadia Benzaquen, David Park, Pamela Egan, Daniel Lebovic, Kristen Pettit, Eric Whitman, Douglas Tremblay, Jonathan Feld, Sarah Buckley, Karisse Roman-Torres, Jennifer Smith, Adam Craig, John Mascarenhas

Einstein Health Papers

IMPORTANCE: The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated.

OBJECTIVE: To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.5 months of safety follow-up per patient. Data analysis was performed …

Examining The Barriers, Facilitators And Attitudes Towards Covid-19 Vaccine And Public Health Measures For Black Communities In Canada: A Qualitative Study Protocol., Obidimma Ezezika, Bethelehem Girmay, Toluwalope Adedugbe, Isaac Jonas, Yanaminah Thullah, Chris Thompson

Health Studies Publications

INTRODUCTION: Black communities claim the highest number of cases and deaths due to COVID-19 in Canada. Generating culturally/contextually appropriate public health measures and strategies for vaccine uptake in black communities within Canada can better support the disproportionate impact of this pandemic. This study explores the barriers and enablers to public health measures limited to mask-wearing, disinfection, sanitation, social distancing and handwashing, as well as the barriers and attitudes towards COVID-19 vaccines among the black community.

METHODS AND ANALYSIS: We will use qualitative approaches informed by the widely accepted Consolidated Framework for Implementation Research (CFIR) to aid our investigation. We will …

Complexity Of Progranulin Mechanisms Of Action In Mesothelioma, Elisa Ventura, Christopher Xie, Simone Buraschi, Antonino Belfiore, Renato V. Iozzo, Antonio Giordano, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Mesothelioma is an aggressive disease with limited therapeutic options. The growth factor progranulin plays a critical role in several cancer models, where it regulates tumor initiation and progression. Recent data from our laboratories have demonstrated that progranulin and its receptor, EphA2, constitute an oncogenic pathway in bladder cancer by promoting motility, invasion and in vivo tumor formation. Progranulin and EphA2 are expressed in mesothelioma cells but their mechanisms of action are not well defined. In addition, there are no data establishing whether the progranulin/EphA2 axis is tumorigenic for mesothelioma cells.

Methods: The expression of progranulin in various mesothelioma cell …

Federated Learning Enables Big Data For Rare Cancer Boundary Detection, 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, Spyridon Bakas

Department of Radiation Oncology Faculty Papers

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically …

Symptom-Driven Inhaled Corticosteroid/Long-Acting Beta-Agonist Therapy For Adult Patients With Asthma Who Are Non-Adherent To Daily Maintenance Inhalers: A Study Protocol For A Pragmatic Randomized Controlled Trial, James G Krings, Kaitlyn M Wojcik, Vanessa Chen, Tejas C Sekhar, Kelly Harris, Abigail Zulich, Kaharu Sumino, Ross Brownson, Eric Lenze, Mario Castro

2020-Current year OA Pubs

BACKGROUND: While inhaled corticosteroids (ICS) are considered the essential foundation of most asthma therapy, ICS inhaler nonadherence is a notoriously common problem and a significant cause of asthma-related morbidity. Partially acknowledging the problem of nonadherence, international organizations recently made paradigm-shifting recommendations that all patients with mild-to-moderate persistent asthma be considered for symptom-driven ICS-containing inhalers rather than relying on adherence to traditional maintenance ICS inhalers and symptom-driven short-acting beta-agonists (SABA). With this new approach, asthma patients are at least exposed to the important anti-inflammatory effects of ICS-containing inhalers when their symptom reliever inhaler is deployed due to acute symptoms.

METHODS: This …

The Prevalence Of Sars-Cov-2 Antibodies Within The Community Of A Private Tertiary University In The Philippines: A Serial Cross Sectional Study, Lourdes S. Tanchanco, Jenica Clarisse Y. Sy, Angel Belle C. Dy, Myla D. Levantino, Arianna Maever L. Amit, John Wong, Kirsten Angeles, John Paul Vergara

Ateneo School of Medicine and Public Health Publications

The COVID-19 pandemic has caused a public health emergency in all sectors of society, including universities and other academic institutions. This study determined the seroprevalence of SARS-CoV-2 antibodies among administrators, faculty, staff, and students of a private tertiary academic institution in the Philippines over a 7 month period. It employed a serial cross-sectional method using qualitative and quantitative COVID-19 antibody test kits. A total of 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021, which coincided with the vaccine roll-out of …

Impact Of International Travel And Diarrhea On Gut Microbiome And Resistome Dynamics, Manish Boolchandani, Kevin S Blake, Drake H Tilley, Miguel M Cabada, Drew J Schwartz, Sanket Patel, Maria Luisa Morales, Rina Meza, Giselle Soto, Sandra D Isidean, Chad K Porter, Mark P Simons, Gautam Dantas

2020-Current year OA Pubs

International travel contributes to the global spread of antimicrobial resistance. Travelers' diarrhea exacerbates the risk of acquiring multidrug-resistant organisms and can lead to persistent gastrointestinal disturbance post-travel. However, little is known about the impact of diarrhea on travelers' gut microbiomes, and the dynamics of these changes throughout travel. Here, we assembled a cohort of 159 international students visiting the Andean city of Cusco, Peru and applied next-generation sequencing techniques to 718 longitudinally-collected stool samples. We find that gut microbiome composition changed significantly throughout travel, but taxonomic diversity remained stable. However, diarrhea disrupted this stability and resulted in an increased abundance …