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Mapping The Immune Environment In Clear Cell Renal Carcinoma By Single-Cell Genomics, Nicholas Borcherding, Ajaykumar Vishwakarma, Andrew P Voigt, Andrew Bellizzi, Jacob Kaplan, Kenneth Nepple, Aliasger K Salem, Russell W Jenkins, Yousef Zakharia, Weizhou Zhang Jan 2021

Mapping The Immune Environment In Clear Cell Renal Carcinoma By Single-Cell Genomics, Nicholas Borcherding, Ajaykumar Vishwakarma, Andrew P Voigt, Andrew Bellizzi, Jacob Kaplan, Kenneth Nepple, Aliasger K Salem, Russell W Jenkins, Yousef Zakharia, Weizhou Zhang

Open Access Publications

Clear cell renal cell carcinoma (ccRCC) is one of the most immunologically distinct tumor types due to high response rate to immunotherapies, despite low tumor mutational burden. To characterize the tumor immune microenvironment of ccRCC, we applied single-cell-RNA sequencing (SCRS) along with T-cell-receptor (TCR) sequencing to map the transcriptomic heterogeneity of 25,688 individual CD45


Structural Insights Into The Disruption Of Tnf-Tnfr1 Signalling By Small Molecules Stabilising A Distorted Tnf, David Mcmillan, Carlos Martinez-Fleites, John Porter, David Fox, Rachel E. Davis, Prashant Mori, Tom Ceska, Bruce Carrington, Alastair Lawson, Tim Bourne, James O'Connell Jan 2021

Structural Insights Into The Disruption Of Tnf-Tnfr1 Signalling By Small Molecules Stabilising A Distorted Tnf, David Mcmillan, Carlos Martinez-Fleites, John Porter, David Fox, Rachel E. Davis, Prashant Mori, Tom Ceska, Bruce Carrington, Alastair Lawson, Tim Bourne, James O'Connell

Faculty Publications

Tumour necrosis factor (TNF) is a trimeric protein which signals through two membrane receptors, TNFR1 and TNFR2. Previously, we identified small molecules that inhibit human TNF by stabilising a distorted trimer and reduce the number of receptors bound to TNF from three to two. Here we present a biochemical and structural characterisation of the small molecule-stabilised TNF-TNFR1 complex, providing insights into how a distorted TNF trimer can alter signalling function. We demonstrate that the inhibitors reduce the binding affinity of TNF to the third TNFR1 molecule. In support of this, we show by X-ray crystallography that the inhibitor-bound, distorted, TNF …


Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook Jan 2021

Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook

Faculty, Staff and Students Publications

Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA …


Distinct Mechanisms Control Genome Recognition By P53 At Its Target Genes Linked To Different Cell Fates., Marina Farkas, Hideharu Hashimoto, Yingtao Bi, Ramana V Davuluri, Lois Resnick-Silverman, James J. Manfredi, Erik W. Debler, Steven B. Mcmahon Jan 2021

Distinct Mechanisms Control Genome Recognition By P53 At Its Target Genes Linked To Different Cell Fates., Marina Farkas, Hideharu Hashimoto, Yingtao Bi, Ramana V Davuluri, Lois Resnick-Silverman, James J. Manfredi, Erik W. Debler, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

The tumor suppressor p53 integrates stress response pathways by selectively engaging one of several potential transcriptomes, thereby triggering cell fate decisions (e.g., cell cycle arrest, apoptosis). Foundational to this process is the binding of tetrameric p53 to 20-bp response elements (REs) in the genome (RRRCWWGYYYN0-13RRRCWWGYYY). In general, REs at cell cycle arrest targets (e.g. p21) are of higher affinity than those at apoptosis targets (e.g., BAX). However, the RE sequence code underlying selectivity remains undeciphered. Here, we identify molecular mechanisms mediating p53 binding to high- and low-affinity REs by showing that key determinants of the code are embedded …


Identification Of 3-Chymotrypsin Like Protease (3clpro) Inhibitors As Potential Anti-Sars-Cov-2 Agents., Vicky Mody, Joanna Ho, Savannah Wills, Ahmed Mawri, Latasha Lawson, Maximilian C C J C Ebert, Guillaume M Fortin, Srujana Rayalam, Shashidharamurthy Taval Jan 2021

Identification Of 3-Chymotrypsin Like Protease (3clpro) Inhibitors As Potential Anti-Sars-Cov-2 Agents., Vicky Mody, Joanna Ho, Savannah Wills, Ahmed Mawri, Latasha Lawson, Maximilian C C J C Ebert, Guillaume M Fortin, Srujana Rayalam, Shashidharamurthy Taval

PCOM Scholarly Works

Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 …


Designing And Undertaking Randomised Implementation Trials: Guide For Researchers, Luke Wolfenden, Robbie Foy, Justin Presseau, Jeremy Grimshaw, Noah Ivers, Byron Powell, Monica Taljaard, John Wiggers, Rachel Sutherland, Nicole Nathan, Christopher Williams, Melanie Kingsland, Andrew Milat, Rebecca Hodder, Sze Lin Yoong Jan 2021

Designing And Undertaking Randomised Implementation Trials: Guide For Researchers, Luke Wolfenden, Robbie Foy, Justin Presseau, Jeremy Grimshaw, Noah Ivers, Byron Powell, Monica Taljaard, John Wiggers, Rachel Sutherland, Nicole Nathan, Christopher Williams, Melanie Kingsland, Andrew Milat, Rebecca Hodder, Sze Lin Yoong

Open Access Publications

No abstract provided.


The Circadian Cryptochrome, Cry1, Is A Pro-Tumorigenic Factor That Rhythmically Modulates Dna Repair., Ayesha A Shafi, Chris M Mcnair, Jennifer J Mccann, Mohammed Alshalalfa, Anton Shostak, Tesa M Severson, Yanyun Zhu, Andre Bergman, Nicolas Gordon, Amy C Mandigo, Saswati N Chand, Peter Gallagher, Emanuela Dylgjeri, Talya S Laufer, Irina A Vasilevskaya, Matthew J Schiewer, Michael Brunner, Felix Y Feng, Wilbert Zwart, Karen E Knudsen Jan 2021

The Circadian Cryptochrome, Cry1, Is A Pro-Tumorigenic Factor That Rhythmically Modulates Dna Repair., Ayesha A Shafi, Chris M Mcnair, Jennifer J Mccann, Mohammed Alshalalfa, Anton Shostak, Tesa M Severson, Yanyun Zhu, Andre Bergman, Nicolas Gordon, Amy C Mandigo, Saswati N Chand, Peter Gallagher, Emanuela Dylgjeri, Talya S Laufer, Irina A Vasilevskaya, Matthew J Schiewer, Michael Brunner, Felix Y Feng, Wilbert Zwart, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required …


Frontiers In Human Factors: Embedding Specialists In Multi-Disciplinary Efforts To Improve Healthcare., Ken Catchpole, Paul Bowie, Sarah Fouquet, Joy Rivera, Sue Hignett Jan 2021

Frontiers In Human Factors: Embedding Specialists In Multi-Disciplinary Efforts To Improve Healthcare., Ken Catchpole, Paul Bowie, Sarah Fouquet, Joy Rivera, Sue Hignett

Manuscripts, Articles, Book Chapters and Other Papers

Despite the application of a huge range of human factors (HF) principles in a growing range of care contexts, there is much more that could be done to realize this expertise for patient benefit, staff well-being and organizational performance. Healthcare has struggled to embrace system safety approaches, misapplied or misinterpreted others, and has stuck to a range of outdated and potentially counter-productive myths even has safety science has developed. One consequence of these persistent misunderstandings is that few opportunities exist in clinical settings for qualified HF professionals. Instead, HF has been applied by clinicians and others, to highly variable degrees-sometimes …


Application Of Systems Dynamics And Group Model Building To Identify Barriers And Facilitators To Acute Care Delivery In A Resource Limited Setting, Fiona Muttalib, Ellis Ballard, Josephine Langton, Sara Malone, Yudy Fonseca, Andreas Hansmann, Kenneth Remy, Peter Hovmand, Allan Doctor Jan 2021

Application Of Systems Dynamics And Group Model Building To Identify Barriers And Facilitators To Acute Care Delivery In A Resource Limited Setting, Fiona Muttalib, Ellis Ballard, Josephine Langton, Sara Malone, Yudy Fonseca, Andreas Hansmann, Kenneth Remy, Peter Hovmand, Allan Doctor

2020-Current year OA Pubs

BACKGROUND: Group model building (GMB) is a method to facilitate shared understanding of structures and relationships that determine system behaviors. This project aimed to determine the feasibility of GMB in a resource-limited setting and to use GMB to describe key barriers and facilitators to effective acute care delivery at a tertiary care hospital in Malawi.

METHODS: Over 1 week, trained facilitators led three GMB sessions with two groups of healthcare providers to facilitate shared understanding of structures and relationships that determine system behaviors. One group aimed to identify factors that impact patient flow in the paediatric special care ward. The …


Microbiome For Mars: Surveying Microbiome Connections To Healthcare With Implications For Long-Duration Human Spaceflight, Virtual Workshop, July 13, 2020, Michael Lapelusa, Dorit Donoviel, Sergio E Branzini, Paul E Carlson, Stephanie Culler, Amrita K Cheema, Rima Kaddurah-Daouk, Denise Kelly, Isabelle De Cremoux, Rob Knight, Rosa Krajmalnik-Brown, Stephen L Mayo, Sarkis K Mazmanian, Emeran A Mayer, Joseph F Petrosino, Keith Garrison Jan 2021

Microbiome For Mars: Surveying Microbiome Connections To Healthcare With Implications For Long-Duration Human Spaceflight, Virtual Workshop, July 13, 2020, Michael Lapelusa, Dorit Donoviel, Sergio E Branzini, Paul E Carlson, Stephanie Culler, Amrita K Cheema, Rima Kaddurah-Daouk, Denise Kelly, Isabelle De Cremoux, Rob Knight, Rosa Krajmalnik-Brown, Stephen L Mayo, Sarkis K Mazmanian, Emeran A Mayer, Joseph F Petrosino, Keith Garrison

Faculty, Staff and Students Publications

The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate to long-duration human space travel. The conference focused on surveying current microbiome research, future endeavors, and how this growing field could broadly impact human health and space exploration. This report summarizes each speaker's presentation in the order presented at the workshop.


Impact Of A Multidisciplinary Workflow On Safety And Management Of Patients With Heparin-Induced Thrombocytopenia, Sheh-Li Chen, Andrew P. Stivers, Jonathan D. Cicci, Tanner L. Hedrick, Marian A. Rollins-Raval, Raj S. Kasthuri, Kalynn A. Northam Jan 2021

Impact Of A Multidisciplinary Workflow On Safety And Management Of Patients With Heparin-Induced Thrombocytopenia, Sheh-Li Chen, Andrew P. Stivers, Jonathan D. Cicci, Tanner L. Hedrick, Marian A. Rollins-Raval, Raj S. Kasthuri, Kalynn A. Northam

Pathology Research and Scholarship

PURPOSE: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin administration. Management strategies are complex and include discontinuing heparin products, initiating alternative anticoagulants, interpreting laboratory test results, documenting heparin allergies, and providing patient education. Medication error reports and a retrospective review conducted at an academic medical center revealed an opportunity for a quality improvement initiative and led to the creation of a multidisciplinary workflow for the management of HIT. In a pre-post study, the impact of the multidisciplinary workflow on the safety and management of HIT was evaluated.

METHODS: The preimplementation group consisted of adult patients tested for suspected HIT …


Towards Digestible Digital Health Solutions: Application Of A Health Literacy Inclusive Development Framework For Peripartum Depression Management, Alexandra Zingg, Tavleen Singh, Sahiti Myneni Jan 2021

Towards Digestible Digital Health Solutions: Application Of A Health Literacy Inclusive Development Framework For Peripartum Depression Management, Alexandra Zingg, Tavleen Singh, Sahiti Myneni

Faculty, Staff and Student Publications

Women of low income and education have lower levels of peripartum depression (PPD) literacy, limiting their ability to recognize symptoms and make informed healthcare decisions. Existing digital solutions and underlying development frameworks for PPD lack an integrative approach addressing health literacy and related disparities. Therefore, we develop an integrative framework for digital content engineering in PPD self-management consisting of (a) user needs analysis, (b) inclusion of eHealth literacy principles (science and health literacy), and (c) mapping user needs to the Behavioral Intervention Technology model. Results revealed that perinatal women seeking mental health care prefer information in multisensory formats, and knowledge …


Pleiotropic Anticoagulant Functions Of Protein S, Consequences For The Clinical Laboratory. Communication From The Ssc Of The Isth, Herm Jan M. Brinkman, Josefin Ahnström, Elisabetta Castoldi, Björn Dahlbäck, Richard A. Marlar Jan 2021

Pleiotropic Anticoagulant Functions Of Protein S, Consequences For The Clinical Laboratory. Communication From The Ssc Of The Isth, Herm Jan M. Brinkman, Josefin Ahnström, Elisabetta Castoldi, Björn Dahlbäck, Richard A. Marlar

Pathology Research and Scholarship

Hereditary deficiencies of protein S (PS) increase the risk of thrombosis. However, assessing the plasma levels of PS is complicated by its manifold physiological interactions, while the large inter-individual variability makes it problematic to establish reliable cut-off values. PS has multiple physiological functions, with only two appearing to have significant anticoagulant properties: the activated protein C (APC) and tissue factor pathway inhibitor alpha (TFPIα) cofactor activities. Current clinical laboratory investigations for deficiency in PS function rely only on the APC-dependent activity. This communication presents an argument for reclassifying the qualitative PS deficiencies to differentiate the two major anticoagulant functions of …


Lying In Wait: The Resurgence Of Dengue Virus After The Zika Epidemic In Brazil, Anderson Fernandes Brito, Lais Ceschini Machado, Rachel J. Oidtman, Márcio Junio Lima Siconelli, Quan Minh Tran, Joseph R. Fauver, Rodrigo Dias De Oliveira Carvalho, Filipe Zimmer Dezordi, Mylena Ribeiro Pereira, Luiza Antunes De Castro-Jorge, Elaine Cristina Manini Minto, Luzia Márcia Romanholi Passos, Chaney C. Kalinich, Mary E. Petrone, Emma Allen, Guido Camargo España, Angkana T. Huang, Derek A. T. Cummings, Guy Baele, Rafael Freitas Oliveira Franca, Benedito Antônio Lopes Da Fonseca, T. Alex Perkins, Gabriel Luz Wallau, Nathan D. Grubaugh Jan 2021

Lying In Wait: The Resurgence Of Dengue Virus After The Zika Epidemic In Brazil, Anderson Fernandes Brito, Lais Ceschini Machado, Rachel J. Oidtman, Márcio Junio Lima Siconelli, Quan Minh Tran, Joseph R. Fauver, Rodrigo Dias De Oliveira Carvalho, Filipe Zimmer Dezordi, Mylena Ribeiro Pereira, Luiza Antunes De Castro-Jorge, Elaine Cristina Manini Minto, Luzia Márcia Romanholi Passos, Chaney C. Kalinich, Mary E. Petrone, Emma Allen, Guido Camargo España, Angkana T. Huang, Derek A. T. Cummings, Guy Baele, Rafael Freitas Oliveira Franca, Benedito Antônio Lopes Da Fonseca, T. Alex Perkins, Gabriel Luz Wallau, Nathan D. Grubaugh

Journal Articles: Epidemiology

After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017-2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017-2018, despite conditions being suitable for viral spread. Our study also shows a marked decline in dengue susceptibility …


Viral Dynamics Of Acute Sars-Cov-2 Infection And Applications To Diagnostic And Public Health Strategies, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Scott W. Olesen, Caroline Tai, Kristin Y. Shiue, Chaney C. Kalinich, Sarah Jednak, Isabel M. Ott, Chantal B. F. Vogels, Jay Wohlgemuth, James Weisberger, John Difiori, Deverick J. Anderson, Jimmie Mancell, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad Jan 2021

Viral Dynamics Of Acute Sars-Cov-2 Infection And Applications To Diagnostic And Public Health Strategies, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Scott W. Olesen, Caroline Tai, Kristin Y. Shiue, Chaney C. Kalinich, Sarah Jednak, Isabel M. Ott, Chantal B. F. Vogels, Jay Wohlgemuth, James Weisberger, John Difiori, Deverick J. Anderson, Jimmie Mancell, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Journal Articles: Epidemiology

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found …


Guidelines For Conducting Virtual Cognitive Interviews During A Pandemic, James A Shepperd, Gabrielle Pogge, Jean M Hunleth, Sienna Ruiz, Erika A Waters Jan 2021

Guidelines For Conducting Virtual Cognitive Interviews During A Pandemic, James A Shepperd, Gabrielle Pogge, Jean M Hunleth, Sienna Ruiz, Erika A Waters

Open Access Publications

The COVID-19 pandemic has challenged researchers working in physical contact with research participants. Cognitive interviews examine whether study components (most often questionnaire items) are worded or structured in a manner that allows study participants to interpret the items in a way intended by the researcher. We developed guidelines to conduct cognitive interviews virtually to accommodate interviewees who have limited access to the internet. The guidelines describe the essential communication and safety equipment requirements and outline a procedure for collecting responses while maintaining the safety of the participants and researchers. Furthermore, the guidelines provide suggestions regarding training of participants to use …


Stroke-Related Alterations In Inter-Areal Communication, Michele Allegra, Chiara Favaretto, Nicholas Metcalf, Maurizio Corbetta, Andrea Brovelli Jan 2021

Stroke-Related Alterations In Inter-Areal Communication, Michele Allegra, Chiara Favaretto, Nicholas Metcalf, Maurizio Corbetta, Andrea Brovelli

Open Access Publications

Beyond causing local ischemia and cell damage at the site of injury, stroke strongly affects long-range anatomical connections, perturbing the functional organization of brain networks. Several studies reported functional connectivity abnormalities parallelling both behavioral deficits and functional recovery across different cognitive domains. FC alterations suggest that long-range communication in the brain is altered after stroke. However, standard FC analyses cannot reveal the directionality and time scale of inter-areal information transfer. We used resting-state fMRI and covariance-based Granger causality analysis to quantify network-level information transfer and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric …


Mr Elastography Demonstrates Reduced White Matter Shear Stiffness In Early-Onset Hydrocephalus, M E Wagshul, J P Mcallister, D D Limbrick Jr, S Yang, W Mowrey, J T Goodrich, A Meiri, D M Morales, A Kobets, R Abbott Jan 2021

Mr Elastography Demonstrates Reduced White Matter Shear Stiffness In Early-Onset Hydrocephalus, M E Wagshul, J P Mcallister, D D Limbrick Jr, S Yang, W Mowrey, J T Goodrich, A Meiri, D M Morales, A Kobets, R Abbott

Open Access Publications

INTRODUCTION: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures.

METHODS: MRE was collected at two imaging sites …


Outcomes Associated With Social Distancing Policies In St Louis, Missouri, During The Early Phase Of The Covid-19 Pandemic, Elvin H. Geng, Joshua Schwab, Randi Foraker, Branson Fox, Christine M. Hoehner, Mario Schootman, Aaloke Mody, William Powderly, Byron Yount, Keith Woeltje, Maya Petersen Jan 2021

Outcomes Associated With Social Distancing Policies In St Louis, Missouri, During The Early Phase Of The Covid-19 Pandemic, Elvin H. Geng, Joshua Schwab, Randi Foraker, Branson Fox, Christine M. Hoehner, Mario Schootman, Aaloke Mody, William Powderly, Byron Yount, Keith Woeltje, Maya Petersen

Open Access Publications

Importance: In the absence of a national strategy in response to the COVID-19 pandemic, many public health decisions fell to local elected officials and agencies. Outcomes of such policies depend on a complex combination of local epidemic conditions and demographic features as well as the intensity and timing of such policies and are therefore unclear.

Objective: To use a decision analytical model of the COVID-19 epidemic to investigate potential outcomes if actual policies enacted in March 2020 (during the first wave of the epidemic) in the St Louis region of Missouri had been delayed.

Design, Setting, and Participants: A previously …


Comprehensive Assessment Of A Nationwide Simulation-Based Course For Artificial Life Support, Mateusz Puslecki, Ahmed S Said, Et Al Jan 2021

Comprehensive Assessment Of A Nationwide Simulation-Based Course For Artificial Life Support, Mateusz Puslecki, Ahmed S Said, Et Al

Open Access Publications

BACKGROUND: Successful implementation of medical technologies applied in life-threatening conditions, including extracorporeal membrane oxygenation (ECMO) requires appropriate preparation and training of medical personnel. The pandemic has accelerated the creation of new ECMO centers and has highlighted continuous training in adapting to new pandemic standards. To reach high standards of patients' care, we created the first of its kind, National Education Centre for Artificial Life Support (NEC-ALS) in 40 million inhabitants' country in the Central and Eastern Europe (CEE). The role of the Center is to test and promote the novel or commonly used procedures as well as to develop staff …


An Absence Of Equipoise: Examining Surgeons' Decision Talk During Encounters With Women Considering Breast Cancer Surgery, Mary C. Politi, Catherine H. Saunders, Victoria F. Grabinski, Renata W. Yen, Amy E. Cyr, Marie-Anne Durand, Glyn Elwyn Jan 2021

An Absence Of Equipoise: Examining Surgeons' Decision Talk During Encounters With Women Considering Breast Cancer Surgery, Mary C. Politi, Catherine H. Saunders, Victoria F. Grabinski, Renata W. Yen, Amy E. Cyr, Marie-Anne Durand, Glyn Elwyn

Open Access Publications

Shared decision-making is recommended for decisions with multiple reasonable options, yet clinicians often subtly or explicitly guide choices. Using purposive sampling, we performed a secondary analysis of 142 audio-recorded encounters between 13 surgeons and women eligible for breast-conserving surgery with radiation or mastectomy. We trained 9 surgeons in shared decision-making and provided them one of two conversation aids; 4 surgeons practiced as usual. Based on a published taxonomy of treatment recommendations (pronouncements, suggestions, proposals, offers, assertions), we examined how surgeons framed choices with patients. Many surgeons made assertions providing information and advice (usual care 71% vs. intervention 66%; p = …


Rubella Virus Infected Macrophages And Neutrophils Define Patterns Of Granulomatous Inflammation In Inborn And Acquired Errors Of Immunity, Ludmila Perelygina, Amy Musiek, Et Al Jan 2021

Rubella Virus Infected Macrophages And Neutrophils Define Patterns Of Granulomatous Inflammation In Inborn And Acquired Errors Of Immunity, Ludmila Perelygina, Amy Musiek, Et Al

Open Access Publications

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, …


Characteristics Of Sars-Cov-2 Transmission Among Meat Processing Workers In Nebraska, Usa, And Effectiveness Of Risk Mitigation Measures, Jocelyn J. Herstein, Abraham Degarege, Derry Stover, Christopher Austin, Michelle M. Schwedhelm, James V. Lawler, John Lowe, Athena K. Ramos, Matthew Donahue Jan 2021

Characteristics Of Sars-Cov-2 Transmission Among Meat Processing Workers In Nebraska, Usa, And Effectiveness Of Risk Mitigation Measures, Jocelyn J. Herstein, Abraham Degarege, Derry Stover, Christopher Austin, Michelle M. Schwedhelm, James V. Lawler, John Lowe, Athena K. Ramos, Matthew Donahue

Journal Articles: Epidemiology

The coronavirus disease (COVID-19) pandemic has severely impacted the meat processing industry in the United States. We sought to detail demographics and outcomes of severe acute respiratory syndrome coronavirus 2 infections among workers in Nebraska meat processing facilities and determine the effects of initiating universal mask policies and installing physical barriers at 13 meat processing facilities. During April 1-July 31, 2020, COVID-19 was diagnosed in 5,002 Nebraska meat processing workers (attack rate 19%). After initiating both universal masking and physical barrier interventions, 8/13 facilities showed a statistically significant reduction in COVID-19 incidence inspecifically, high attack rates among meat processing industry …


Joseph Smith’S Translation: The Words And Worlds Of Early Mormonism, Samuel Morris Brown, Kent P. Jackson, Reviewer Jan 2021

Joseph Smith’S Translation: The Words And Worlds Of Early Mormonism, Samuel Morris Brown, Kent P. Jackson, Reviewer

BYU Studies

Samuel Morris Brown’s Joseph Smith’s Translation: The Words and Worlds of Early Mormonism announces a sweeping objective: to place all of Joseph Smith’s prophetic projects under a single heading: translation. The thesis of the book is that “translation as a source of scriptural texts” is mirrored in “translation as a process by which humans became assimilable to the divine presence” (ix). “Translation was about more than words and sentences. Translation was also concerned with the transformation of human beings and the worlds they were capable of inhabiting. These twin senses of translation run together in early Latter-day Saint thought” (4).


Evaluation Of A Clinical Decision Support Strategy To Increase Seasonal Influenza Vaccination Among Hospitalized Children Before Inpatient Discharge, Evan W. Orenstein, Omar Elsayed-Ali, Swaminathan Kandaswamy, Erin Masterson, Reena Blanco, Pareen Shah, Patricia Lantis, Amy Kolwaite, Thomas E. Dawson, Edwin Ray, Christy Bryant, Srikant Iyer, Andi L. Shane, Stephanie Jernigan Jan 2021

Evaluation Of A Clinical Decision Support Strategy To Increase Seasonal Influenza Vaccination Among Hospitalized Children Before Inpatient Discharge, Evan W. Orenstein, Omar Elsayed-Ali, Swaminathan Kandaswamy, Erin Masterson, Reena Blanco, Pareen Shah, Patricia Lantis, Amy Kolwaite, Thomas E. Dawson, Edwin Ray, Christy Bryant, Srikant Iyer, Andi L. Shane, Stephanie Jernigan

Open Access Publications

Importance: Hospitalized children are at increased risk of influenza-related complications, yet influenza vaccine coverage remains low among this group. Evidence-based strategies about vaccination of vulnerable children during all health care visits are especially important during the COVID-19 pandemic.

Objective: To design and evaluate a clinical decision support (CDS) strategy to increase the proportion of eligible hospitalized children who receive a seasonal influenza vaccine prior to inpatient discharge.

Design, Setting, and Participants: This quality improvement study was conducted among children eligible for the seasonal influenza vaccine who were hospitalized in a tertiary pediatric health system providing care to more than half …


Lesion Quantification Toolkit: A Matlab Software Tool For Estimating Grey Matter Damage And White Matter Disconnections In Patients With Focal Brain Lesions, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman Jan 2021

Lesion Quantification Toolkit: A Matlab Software Tool For Estimating Grey Matter Damage And White Matter Disconnections In Patients With Focal Brain Lesions, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman

Open Access Publications

Lesion studies are an important tool for cognitive neuroscientists and neurologists. However, while brain lesion studies have traditionally aimed to localize neurological symptoms to specific anatomical loci, a growing body of evidence indicates that neurological diseases such as stroke are best conceptualized as brain network disorders. While researchers in the fields of neuroscience and neurology are therefore increasingly interested in quantifying the effects of focal brain lesions on the white matter connections that form the brain's structural connectome, few dedicated tools exist to facilitate this endeavor. Here, we present the Lesion Quantification Toolkit, a publicly available MATLAB software package for …


Brain/Minds Beyond Human Brain Mri Project: A Protocol For Multi-Level Harmonization Across Brain Disorders Throughout The Lifespan, Shinsuke Koike, Matthew F Glasser, David C Van Essen, Et Al Jan 2021

Brain/Minds Beyond Human Brain Mri Project: A Protocol For Multi-Level Harmonization Across Brain Disorders Throughout The Lifespan, Shinsuke Koike, Matthew F Glasser, David C Van Essen, Et Al

Open Access Publications

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing …


Improvements To A Framework For Gender And Emerging Infectious Diseases, Lynn Lieberman Lawry, Roberta Lugo-Robles, Vicki Mciver Jan 2021

Improvements To A Framework For Gender And Emerging Infectious Diseases, Lynn Lieberman Lawry, Roberta Lugo-Robles, Vicki Mciver

Journal Articles: Epidemiology

No abstract provided.


A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells Jan 2021

A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells

Journal Articles: Infectious Diseases

During the COVID-19 pandemic, HIV clinics had to transform care delivery for people with HIV (PWH). We developed a multifaceted telehealth implementation strategy and monitored number of out of care patients (OOC), medical visit frequency (MVF), gap in care (GiC) and viral suppression (VS), and compared measures to baseline data. Between April and October 2020, 1559 visits were scheduled; 328 (21%) were missed, and 63 (4%) were new to care. Of the remaining 1168 follow-up visits, 412 (35%) were telehealth visits. As of October 2020, there were 53 patients OOC, MVF was 55% and GiC was 24% compared to 34, …


Science Dialogue Mapping Of Knowledge And Knowledge Gaps Related To The Effects Of Dairy Intake On Human Cardiovascular Health And Disease, Andrew W Brown, Kathryn A Kaiser, Andrew Keitt, Kevin Fontaine, Madeline Gibson, Barbara A Gower, James M Shikany, Colby J Vorland, Donald C Beitz, Dennis M Bier, J Thomas Brenna, David R Jacobs, Penny Kris-Etherton, Kevin Maki, Michael Miller, Marie-Pierre St-Onge, Margarita Teran-Garcia, David B Allison Jan 2021

Science Dialogue Mapping Of Knowledge And Knowledge Gaps Related To The Effects Of Dairy Intake On Human Cardiovascular Health And Disease, Andrew W Brown, Kathryn A Kaiser, Andrew Keitt, Kevin Fontaine, Madeline Gibson, Barbara A Gower, James M Shikany, Colby J Vorland, Donald C Beitz, Dennis M Bier, J Thomas Brenna, David R Jacobs, Penny Kris-Etherton, Kevin Maki, Michael Miller, Marie-Pierre St-Onge, Margarita Teran-Garcia, David B Allison

Children’s Nutrition Research Center Staff Publications

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, “dialogue mapping™,” to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products, 1) should be …