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The Mechanisms Of Action Of Tumor Treating Fields, Justin C Moser, Ellaine Salvador, Karina Deniz, Kenneth Swanson, Jack Tuszynski, Narasimha Kumar Karanam, Michael Story, Emil Lou, Carsten Hagemann Oct 2022

The Mechanisms Of Action Of Tumor Treating Fields, Justin C Moser, Ellaine Salvador, Karina Deniz, Kenneth Swanson, Jack Tuszynski, Narasimha Kumar Karanam, Michael Story, Emil Lou, Carsten Hagemann

Faculty, Staff and Student Publications

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of …


Hsf1 Is A Driver Of Leukemia Stem Cell Self-Renewal In Acute Myeloid Leukemia, Qianze Dong, Nick Borcherding, Et Al. Oct 2022

Hsf1 Is A Driver Of Leukemia Stem Cell Self-Renewal In Acute Myeloid Leukemia, Qianze Dong, Nick Borcherding, Et Al.

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML is that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target in cancer therapy. Using genetic Hsf1 deletion and a direct HSF1 small molecule inhibitor, we show that HSF1 is specifically required for the maintenance of AML, while sparing steady-state and stressed hematopoiesis. Mechanistically, deletion of Hsf1 dysregulates multifaceted genes involved in LSC stemness and suppresses mitochondrial oxidative phosphorylation through downregulation of …


Federated Learning Algorithms For Generalized Mixed-Effects Model (Glmm) On Horizontally Partitioned Data From Distributed Sources, Yong Chen, Xiaoqian Jiang Oct 2022

Federated Learning Algorithms For Generalized Mixed-Effects Model (Glmm) On Horizontally Partitioned Data From Distributed Sources, Yong Chen, Xiaoqian Jiang

Faculty, Staff and Student Publications

OBJECTIVES: This paper developed federated solutions based on two approximation algorithms to achieve federated generalized linear mixed effect models (GLMM). The paper also proposed a solution for numerical errors and singularity issues. And showed the two proposed methods can perform well in revealing the significance of parameter in distributed datasets, comparing to a centralized GLMM algorithm from R package ('lme4') as the baseline model.

METHODS: The log-likelihood function of GLMM is approximated by two numerical methods (Laplace approximation and Gaussian Hermite approximation, abbreviated as LA and GH), which supports federated decomposition of GLMM to bring computation to data. To solve …


2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Arianna Di Napoli, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos Oct 2022

2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Arianna Di Napoli, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos

Faculty, Staff and Student Publications

BACKGROUND: Laboratory and clinical research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3rd World Consensus Conference on BIA-ALCL.

OBJECTIVES: The authors sought to provide practice recommendations from a consensus of experts, supplemented with a literature review regarding epidemiology, etiology, pathogenesis, diagnosis, treatment, socio-psychological aspects, and international authority guidance.

METHODS: A literature search of all manuscripts between 1997 and August 2021 for the above areas of BIA-ALCL was conducted with the PubMed database. Manuscripts in different languages, on non-human subjects, and/or discussing …


Structural And Functional Diversity Of Type Iv Secretion Systems, Elena Evdokimova, Junko Yano, Paul L Fidel, Alexei Savchenko, David R Andes, Peter J Stogios, Michael C Lorenz, Danielle A Garsin Oct 2022

Structural And Functional Diversity Of Type Iv Secretion Systems, Elena Evdokimova, Junko Yano, Paul L Fidel, Alexei Savchenko, David R Andes, Peter J Stogios, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also …


Amyloid Β, Lipid Metabolism, Basal Cholinergic System, And Therapeutics In Alzheimer's Disease, Victoria Campos-Peña, Pavel Pichardo-Rojas, Talía Sánchez-Barbosa, Emma Ortíz-Islas, Citlali Ekaterina Rodríguez-Pérez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios Oct 2022

Amyloid Β, Lipid Metabolism, Basal Cholinergic System, And Therapeutics In Alzheimer's Disease, Victoria Campos-Peña, Pavel Pichardo-Rojas, Talía Sánchez-Barbosa, Emma Ortíz-Islas, Citlali Ekaterina Rodríguez-Pérez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios

2020-Current year OA Pubs

The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each …


Whole Genome Sequence Analysis Of Blood Lipid Levels In >66,000 Individuals, David Y Zhang, Joshua C Bis, Jennifer A Brody, Brian E Cade, Lee-Ming Chuang, Ren-Hua Chung, Joanne E Curran, Lisa De Las Fuentes, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Mariaelisa Graff, Xiuqing Guo, Nancy Heard-Costa, Bertha Hidalgo, Chii-Min Hwu, Marguerite R Irvin, Tanika N Kelly, Leslie Lange, Xiaohui Li, Martin Lisa, Steven A Lubitz, Ani W Manichaikul, Preuss Michael, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Muagututia S Reupena, Jennifer A Smith, Xiao Sun, Kent D Taylor, Russell P Tracy, Michael Y Tsai, Zhe Wang, Yuxuan Wang, Wei Bao, John T Wilkins, Lisa R Yanek, Wei Zhao, Donna K Arnett, John Blangero, Eric Boerwinkle, Donald W Bowden, Yii-Der Ida Chen, Adolfo Correa, L Adrienne Cupples, Susan K Dutcher, Patrick T Ellinor, Myriam Fornage, Stacey Gabriel, Soren Germer, Richard Gibbs, Jiang He, Robert C Kaplan, Sharon L R Kardia, Ryan Kim, Charles Kooperberg, Ruth J F Loos, Karine A Viaud-Martinez, Rasika A Mathias, Stephen T Mcgarvey, Braxton D Mitchell, Deborah Nickerson, Kari E North, Bruce M Psaty, Susan Redline, Alexander P Reiner, Ramachandran S Vasan, Stephen S Rich, Cristen Willer, Jerome I Rotter, Daniel J Rader, Xihong Lin, Gina M Peloso, Pradeep Natarajan Oct 2022

Whole Genome Sequence Analysis Of Blood Lipid Levels In >66,000 Individuals, David Y Zhang, Joshua C Bis, Jennifer A Brody, Brian E Cade, Lee-Ming Chuang, Ren-Hua Chung, Joanne E Curran, Lisa De Las Fuentes, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Mariaelisa Graff, Xiuqing Guo, Nancy Heard-Costa, Bertha Hidalgo, Chii-Min Hwu, Marguerite R Irvin, Tanika N Kelly, Leslie Lange, Xiaohui Li, Martin Lisa, Steven A Lubitz, Ani W Manichaikul, Preuss Michael, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Muagututia S Reupena, Jennifer A Smith, Xiao Sun, Kent D Taylor, Russell P Tracy, Michael Y Tsai, Zhe Wang, Yuxuan Wang, Wei Bao, John T Wilkins, Lisa R Yanek, Wei Zhao, Donna K Arnett, John Blangero, Eric Boerwinkle, Donald W Bowden, Yii-Der Ida Chen, Adolfo Correa, L Adrienne Cupples, Susan K Dutcher, Patrick T Ellinor, Myriam Fornage, Stacey Gabriel, Soren Germer, Richard Gibbs, Jiang He, Robert C Kaplan, Sharon L R Kardia, Ryan Kim, Charles Kooperberg, Ruth J F Loos, Karine A Viaud-Martinez, Rasika A Mathias, Stephen T Mcgarvey, Braxton D Mitchell, Deborah Nickerson, Kari E North, Bruce M Psaty, Susan Redline, Alexander P Reiner, Ramachandran S Vasan, Stephen S Rich, Cristen Willer, Jerome I Rotter, Daniel J Rader, Xihong Lin, Gina M Peloso, Pradeep Natarajan

Faculty, Staff and Student Publications

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid …


Collaborative Quality Improvement Strategy In Secondary Prevention Of Cardiovascular Disease In India: Findings From A Multi-Stakeholder, Qualitative Study Using Consolidated Framework For Implementation Research (Cfir), Kavita Singh, Mark D. Huffman, Leslie C M Johnson, Nikhil Tandon, Dorairaj Prabhakaran, Emily Mendenhall Oct 2022

Collaborative Quality Improvement Strategy In Secondary Prevention Of Cardiovascular Disease In India: Findings From A Multi-Stakeholder, Qualitative Study Using Consolidated Framework For Implementation Research (Cfir), Kavita Singh, Mark D. Huffman, Leslie C M Johnson, Nikhil Tandon, Dorairaj Prabhakaran, Emily Mendenhall

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent in India, and little is known about the perception of patients and providers about a package of collaborative quality improvement (C-QIP) strategies consisting of provider-focused electronic health records-decision support system (EHR-DSS), non-physician health workers (NPHW), and patient-facing text messages to enhance the CVD care.

OBJECTIVE: To explore the barriers and enablers of the C-QIP strategy from the perspective of providers, health administrators, patients, and care givers in India.

METHODS: We conducted a qualitative study using the consolidated framework for implementation research (CFIR) to understand the challenges and facilitators of implementing C-QIP strategy to …


Evolution And Modulation Of Antigen-Specific T Cell Responses In Melanoma Patients, Jani Huuhtanen, Liang Chen, Emmi Jokinen, Henna Kasanen, Tapio Lönnberg, Katriina Peltola, Chunlin Wang, Cassian Yee, Harri Lähdesmäki, Mark M Davis, Satu Mustjoki Oct 2022

Evolution And Modulation Of Antigen-Specific T Cell Responses In Melanoma Patients, Jani Huuhtanen, Liang Chen, Emmi Jokinen, Henna Kasanen, Tapio Lönnberg, Katriina Peltola, Chunlin Wang, Cassian Yee, Harri Lähdesmäki, Mark M Davis, Satu Mustjoki

Faculty, Staff and Student Publications

Analyzing antigen-specific T cell responses at scale has been challenging. Here, we analyze three types of T cell receptor (TCR) repertoire data (antigen-specific TCRs, TCR-repertoire, and single-cell RNA + TCRαβ-sequencing data) from 515 patients with primary or metastatic melanoma and compare it to 783 healthy controls. Although melanoma-associated antigen (MAA) -specific TCRs are restricted to individuals, they share sequence similarities that allow us to build classifiers for predicting anti-MAA T cells. The frequency of anti-MAA T cells distinguishes melanoma patients from healthy and predicts metastatic recurrence from primary melanoma. Anti-MAA T cells have stem-like properties and frequent interactions with regulatory …


Occupational Characteristics Associated With Sars-Cov-2 Infection In The Uk Biobank During August-November 2020: A Cohort Study, Elizabeth L Yanik, Bradley A Evanoff, Ann Marie Dale, Yinjiao Ma, Karen E Walker-Bone Oct 2022

Occupational Characteristics Associated With Sars-Cov-2 Infection In The Uk Biobank During August-November 2020: A Cohort Study, Elizabeth L Yanik, Bradley A Evanoff, Ann Marie Dale, Yinjiao Ma, Karen E Walker-Bone

2020-Current year OA Pubs

BACKGROUND: Occupational exposures may play a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk. We used a job-exposure matrix linked to the UK Biobank to measure occupational characteristics and estimate associations with a positive SARS-CoV-2 test.

METHODS: People reporting job titles at their baseline interview in England who were < 65 years of age in 2020 were included. Healthcare workers were excluded because of differential access to testing. Jobs were linked to the US Occupational Information Network (O*NET) job exposure matrix. O*NET-based scores were examined for occupational physical proximity, exposure to diseases/infection, working outdoors exposed to weather, and working outdoors under cover (score range = 1-5). Jobs were classified as remote work using two algorithms. SARS-CoV-2 test results were evaluated between August 5th-November 10th, 2020, when the UK was released from lockdown. Cox regression was used to calculate adjusted hazard ratios (aHRs), accounting for age, sex, race, education, neighborhood deprivation, assessment center, household size, and income.

RESULTS: We included 115,451 people with job titles, of whom 1746 tested positive for SARS-CoV-2. A one-point increase in physical proximity score was associated with 1.14 times higher risk of SARS-CoV-2 (95%CI = 1.05-1.24). A one-point increase in the exposure to diseases/infections score was associated with 1.09 …


Near-Peers Effectively Teach Clinical Documentation Skills To Early Medical Students, Stephanie Sherman, Nadia Ismail Oct 2022

Near-Peers Effectively Teach Clinical Documentation Skills To Early Medical Students, Stephanie Sherman, Nadia Ismail

Faculty, Staff and Students Publications

BACKGROUND: Composing the History of Present Illness (HPI), a key component of medical communication, requires critical thinking. Small group learning strategies have demonstrated superior effectiveness at developing critical thinking skills. Finding sufficient faculty facilitators for small groups remains a major gap in implementing these sessions. We hypothesized that "near-peer" teachers could effectively teach HPI documentation skills and fill the gap of small group facilitators. Here, we present a head-to-head comparison of near-peer and faculty teaching outcomes.

METHODS: Second-year medical students in a single institution participated in an HPI Workshop as a clinical skills course requirement. Students were randomly assigned a …


Near-Peers Effectively Teach Clinical Documentation Skills To Early Medical Students, Stephanie Sherman, Nadia Ismail Oct 2022

Near-Peers Effectively Teach Clinical Documentation Skills To Early Medical Students, Stephanie Sherman, Nadia Ismail

Faculty, Staff and Students Publications

Background: Composing the History of Present Illness (HPI), a key component of medical communication, requires critical thinking. Small group learning strategies have demonstrated superior effectiveness at developing critical thinking skills. Finding sufficient faculty facilitators for small groups remains a major gap in implementing these sessions. We hypothesized that "near-peer" teachers could effectively teach HPI documentation skills and fill the gap of small group facilitators. Here, we present a head-to-head comparison of near-peer and faculty teaching outcomes.

Methods: Second-year medical students in a single institution participated in an HPI Workshop as a clinical skills course requirement. Students were randomly assigned a …


Functional Genomics Of Complex Cancer Genomes., Francesca Menghi, Edison Liu Oct 2022

Functional Genomics Of Complex Cancer Genomes., Francesca Menghi, Edison Liu

Faculty Research 2022

Cancer functional genomics is the study of how genetic, epigenetic, and transcriptional alterations affect cancer phenotypes, such as growth and therapeutic response. Here, we comment on how, taking advantage of next generation sequencing, functional genomics, often combined with systems biology approaches, has revealed novel cancer vulnerabilities beyond the original paradigm of one gene-one phenotype.


Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021., Ariana Perez, Joana Y. Lively, Aaron Curns, Geoffrey A. Weinberg, Natasha B. Halasa, Mary Allen Staat, Peter G. Szilagyi, Laura S. Stewart, Monica M. Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L. Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A. Englund, Eileen J. Klein, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Gayle E. Langley, Susan I. Gerber, Angela Campbell, Aron J. Hall, Brian Rha, Meredith Mcmorrow, New Vaccine Surveillance Network Collaborators Oct 2022

Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021., Ariana Perez, Joana Y. Lively, Aaron Curns, Geoffrey A. Weinberg, Natasha B. Halasa, Mary Allen Staat, Peter G. Szilagyi, Laura S. Stewart, Monica M. Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L. Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A. Englund, Eileen J. Klein, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Gayle E. Langley, Susan I. Gerber, Angela Campbell, Aron J. Hall, Brian Rha, Meredith Mcmorrow, New Vaccine Surveillance Network Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …


Infant Behavioral State And Stool Microbiome In Infants Receiving Lactocaseibacillus Rhamnosus Gg In Formula: Randomized Controlled Trial, Cheryl L Harris, Jennifer L Wampler, Nicholas A Bokulich, Carol Lynn Berseth Oct 2022

Infant Behavioral State And Stool Microbiome In Infants Receiving Lactocaseibacillus Rhamnosus Gg In Formula: Randomized Controlled Trial, Cheryl L Harris, Jennifer L Wampler, Nicholas A Bokulich, Carol Lynn Berseth

Faculty, Staff and Students Publications

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).

METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with …


Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021, Natasha B Halasa, Monica M Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A Englund, Eileen J Klein, Rangaraj Selvarangan, Christopher J Harrison, Julie A Boom, Leila C Sahni, Marian G Michaels, John V Williams, Gayle E Langley, Susan I Gerber, Angela Campbell, Aron J Hall, Brian Rha, Meredith Mcmorrow Oct 2022

Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021, Natasha B Halasa, Monica M Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A Englund, Eileen J Klein, Rangaraj Selvarangan, Christopher J Harrison, Julie A Boom, Leila C Sahni, Marian G Michaels, John V Williams, Gayle E Langley, Susan I Gerber, Angela Campbell, Aron J Hall, Brian Rha, Meredith Mcmorrow

Faculty, Staff and Student Publications

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …


The Recurrent De Novo C.2011c>T Missense Variant In Mtss2 Causes Syndromic Intellectual Disability, Yan Huang, Gabrielle Lemire, Lauren C Briere, Fang Liu, Marja W Wessels, Xueqi Wang, Matthew Osmond, Oguz Kanca, Shenzhao Lu, Frances A High, Melissa A Walker, Lance H Rodan, Undiagnosed Diseases Network, Care4rare Canada Consortium, Kristin D Kernohan, David A Sweetser, Kym M Boycott, Hugo J Bellen Oct 2022

The Recurrent De Novo C.2011c>T Missense Variant In Mtss2 Causes Syndromic Intellectual Disability, Yan Huang, Gabrielle Lemire, Lauren C Briere, Fang Liu, Marja W Wessels, Xueqi Wang, Matthew Osmond, Oguz Kanca, Shenzhao Lu, Frances A High, Melissa A Walker, Lance H Rodan, Undiagnosed Diseases Network, Care4rare Canada Consortium, Kristin D Kernohan, David A Sweetser, Kym M Boycott, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

MTSS2, also known as MTSS1L, binds to plasma membranes and modulates their bending. MTSS2 is highly expressed in the central nervous system (CNS) and appears to be involved in activity-dependent synaptic plasticity. Variants in MTSS2 have not yet been associated with a human phenotype in OMIM. Here we report five individuals with the same heterozygous de novo variant in MTSS2 (GenBank: NM_138383.2: c.2011C>T [p.Arg671Trp]) identified by exome sequencing. The individuals present with global developmental delay, mild intellectual disability, ophthalmological anomalies, microcephaly or relative microcephaly, and shared mild facial dysmorphisms. Immunoblots of fibroblasts from two affected individuals revealed that the …


Effectiveness And Feasibility Of Telerehabilitation In Patients With Covid-19: A Systematic Review And Meta-Analysis Oct 2022

Effectiveness And Feasibility Of Telerehabilitation In Patients With Covid-19: A Systematic Review And Meta-Analysis

Faculty, Staff and Student Publications

OBJECTIVES: To determine the pooled effectiveness and feasibility of telerehabilitation in patients with COVID-19.

DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs).

DATA SOURCES: PubMed, CINAHL, Science Direct, PEDro, Google Scholar and Cochrane Library databases were systematically searched to the end of March 2022.

ELIGIBILITY CRITERIA AND OUTCOMES: RCTs investigating the effects of telerehabilitation in the management of patients with COVID-19 were included. The outcomes of interest were functional capacity, cardiopulmonary exercise tests, quality of life and other variables where data are available.

DATA EXTRACTION AND SYNTHESIS: Two reviewers screened, extracted data and performed methodological quality assessment independently. …


Global Longitudinal Strain And Biomarkers Of Cardiac Damage And Stress As Predictors Of Outcomes After Transcatheter Aortic Valve Implantation, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al. Oct 2022

Global Longitudinal Strain And Biomarkers Of Cardiac Damage And Stress As Predictors Of Outcomes After Transcatheter Aortic Valve Implantation, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al.

2020-Current year OA Pubs

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (


Association Between The Affordable Care Act Medicaid Expansion And Receipt Of Cardiac Resynchronization Therapy By Race And Ethnicity, Hunter Mwansa, Ibrahim Barry, Shannon M Knapp, Sula Mazimba, Elizabeth Calhoun, Nancy K Sweitzer, Khadijah Breathett Oct 2022

Association Between The Affordable Care Act Medicaid Expansion And Receipt Of Cardiac Resynchronization Therapy By Race And Ethnicity, Hunter Mwansa, Ibrahim Barry, Shannon M Knapp, Sula Mazimba, Elizabeth Calhoun, Nancy K Sweitzer, Khadijah Breathett

2020-Current year OA Pubs

Background Black and Hispanic patients are less likely to receive cardiac resynchronization therapy (CRT) than White patients. Medicaid expansion has been associated with increased access to cardiovascular care among racial and ethnic groups with higher prevalence of underinsurance. It is unknown whether the Medicaid expansion was associated with increased receipt of CRT by race and ethnicity. Methods and Results Using Healthcare Cost and Utilization Project Data State Inpatient Databases from 19 states and Washington, DC, we analyzed 1061 patients from early-adopter states (Medicaid expansion by January 2014) and 745 patients from nonadopter states (no implementation 2013-2014). Estimates of change in …


Racial And Ethnic Differences In The Association Of Low-Carbohydrate Diet With Mortality In The Multi-Ethnic Study Of Atherosclerosis, Seung-Won Oh, Alexis C Wood, Seung-Sik Hwang, Matthew Allison Oct 2022

Racial And Ethnic Differences In The Association Of Low-Carbohydrate Diet With Mortality In The Multi-Ethnic Study Of Atherosclerosis, Seung-Won Oh, Alexis C Wood, Seung-Sik Hwang, Matthew Allison

Children’s Nutrition Research Center Staff Publications

Importance: Evidence linking low-carbohydrate diets (LCDs) to mortality is limited among multiethnic populations.

Objective: To evaluate the association between LCDs and mortality by race and ethnicity.

Design, setting, and participants: The Multi-Ethnic Study of Atherosclerosis is a large, population-based prospective cohort study of adults aged 45 to 84 years recruited from 6 US communities. A total of 6109 participants without baseline cardiovascular disease were included in this analysis. Baseline data were collected from July 2000 to August 2002, with follow-up completed by December 2017. The data were analyzed between May 2021 and April 2022.

Exposures: Food frequency questionnaires were used …


Covid-19 Pandemic And Infant Neurodevelopmental Impairment: A Systematic Review And Meta-Analysis, Enrico R Barrozo, Abolfazl Shirdel Abdolmaleki, Sara E Arian, Nikan Zargarzadeh, Lara S Shekerdemian, Kjersti M Aagaard, Alireza A Shamshirsaz Oct 2022

Covid-19 Pandemic And Infant Neurodevelopmental Impairment: A Systematic Review And Meta-Analysis, Enrico R Barrozo, Abolfazl Shirdel Abdolmaleki, Sara E Arian, Nikan Zargarzadeh, Lara S Shekerdemian, Kjersti M Aagaard, Alireza A Shamshirsaz

Faculty, Staff and Students Publications

IMPORTANCE: Primary studies proposed that aberrant maternal antiviral immunity and/or giving birth in quarantine, such as during the ongoing COVID-19 pandemic, may be associated with the risk of neurodevelopmental impairment (NDI) in offspring.

OBJECTIVES: To evaluate the associations of birth and being raised during the COVID-19 pandemic with risk of NDI among infants and to assess the association of gestational exposure to SARS-CoV-2 with risk of NDI.

DATA SOURCES: PubMed, Web of Science, Scopus, Embase, and preprint servers were systematically searched from inception to March 25, 2022.

STUDY SELECTION: Studies evaluating the neurodevelopment of infants born during the SARS-CoV-2 pandemic …


Current Communication Practices Between Obstetrics And Gynecology Residency Applicants And Program Directors, Helen Kang Morgan, Abigail Ford Winkel, Karen George, Eric Strand, Erika Banks, Fiona Byrne, David Marzano, Maya M Hammoud Oct 2022

Current Communication Practices Between Obstetrics And Gynecology Residency Applicants And Program Directors, Helen Kang Morgan, Abigail Ford Winkel, Karen George, Eric Strand, Erika Banks, Fiona Byrne, David Marzano, Maya M Hammoud

2020-Current year OA Pubs

Importance: In order to equitably improve the residency application process, it is essential to understand the problems we need to address.

Objective: To determine how obstetrics and gynecology (OBGYN) applicants and faculty communicate applicants' interest to residency programs, and how program directors report being influenced by these communications.

Design, Setting, and Participants: This survey study was conducted with email surveys of OBGYN application stakeholders in 2022. Included participants were OBGYN applicants, clerkship directors, and residency program directors in medical education associations' email listservs.

Exposures: Surveys sent by the American Association of Medical Colleges, Association of Professors of Gynecology and Obstetrics, …


Autosomal Recessive Lrp1-Related Syndrome Featuring Cardiopulmonary Dysfunction, Bone Dysmorphology, And Corneal Clouding., Paul R Mark, Stephen A Murray, Tao Yang, Alexandra Eby, Angela Lai, Di Lu, Jacob Zieba, Surender Rajasekaran, Elizabeth A Vansickle, Linda Z Rossetti, Lucia Guidugli, Kelly Watkins, Meredith S Wright, Caleb P Bupp, Jeremy W Prokop Oct 2022

Autosomal Recessive Lrp1-Related Syndrome Featuring Cardiopulmonary Dysfunction, Bone Dysmorphology, And Corneal Clouding., Paul R Mark, Stephen A Murray, Tao Yang, Alexandra Eby, Angela Lai, Di Lu, Jacob Zieba, Surender Rajasekaran, Elizabeth A Vansickle, Linda Z Rossetti, Lucia Guidugli, Kelly Watkins, Meredith S Wright, Caleb P Bupp, Jeremy W Prokop

Faculty Research 2022

We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including corneal clouding and ascites. Both siblings had compound heterozygous damaging variants, c.11420G > C (p.Cys3807Ser) and c.12407T > G (p.Val4136Gly) in


Global Learning For Health Equity: A Literature Review, Yolanda Ogbolu, Ruth Dudding, Kevin Fiori, Janette North-Kabore, Dana Parke, Rev A. Plum, Sonya Shin, Virginia Rowthorn Oct 2022

Global Learning For Health Equity: A Literature Review, Yolanda Ogbolu, Ruth Dudding, Kevin Fiori, Janette North-Kabore, Dana Parke, Rev A. Plum, Sonya Shin, Virginia Rowthorn

Public Health Sciences Articles

BACKGROUND: In high income countries struggling with escalating health care costs and persistent lack of equity, there is growing interest in searching for innovative solutions developed outside national borders, particularly in low- and middle-income countries (LMICs). Engaging with global ideas to apply them to local health equity challenges is becoming increasingly recognized as an approach to shift the health equity landscape in the United States (US) in a significant way. No single name or set of practices yet defines the process of identifying LMIC interventions for adaptation; implementing interventions in high-income countries (HIC) settings; or evaluating the implementation of such …


Antimicrobial Stewardship For Sepsis In The Intensive Care Unit: Survey Of Critical Care And Infectious Diseases Physicians, M Cristina Vazquez Guillamet, Jason P Burnham, Maria Pérez, Marin H Kollef, Constantine A Manthous, Donna B Jeffe Oct 2022

Antimicrobial Stewardship For Sepsis In The Intensive Care Unit: Survey Of Critical Care And Infectious Diseases Physicians, M Cristina Vazquez Guillamet, Jason P Burnham, Maria Pérez, Marin H Kollef, Constantine A Manthous, Donna B Jeffe

2020-Current year OA Pubs

OBJECTIVE: To evaluate the attitudes of infectious diseases (ID) and critical care physicians toward antimicrobial stewardship in the intensive care unit (ICU).

DESIGN: Anonymous, cross-sectional, web-based surveys.

SETTING: Surveys were completed in March-November 2017, and data were analyzed from December 2017 to December 2019.

PARTICIPANTS: ID and critical care fellows and attending physicians.

METHODS: We included 10 demographic and 17 newly developed, 5-point, Likert-scaled items measuring attitudes toward ICU antimicrobial stewardship and transdisciplinary collaboration. Exploratory principal components analysis (PCA) was used for data reduction. Multivariable linear regression models explored demographic and attitudinal variables.

RESULTS: Of 372 respondents, 315 physicians had …


Considerations For Partnering With Ryan White Case Managers To Create Equitable Opportunities For People With Hiv To Participate In Research, Elizabeth Lockhart, Deanne Turner, Jerome T. Galea, Stephanie L. Marhefka Oct 2022

Considerations For Partnering With Ryan White Case Managers To Create Equitable Opportunities For People With Hiv To Participate In Research, Elizabeth Lockhart, Deanne Turner, Jerome T. Galea, Stephanie L. Marhefka

Center for Health Policy and Health Services Research Articles

Many research studies focus on recruitment from one or few HIV clinics or internet-engaged populations, but this may result in inequitable representation of people with HIV (PWH), across the rural/urban/suburban continuum. Ryan White Case Managers (RWCM) meet regularly with PWH, potentially positioning them as partners in gathering research-related data from diverse groups of low-income, marginalized, PWH. Yet, data collection in partnership with RWCM, particularly over large geographic areas, has been under-explored. We partnered with RWCM and their organizations throughout Florida to administer a 10-item technology use and willingness survey to clients living with HIV; RWCMs provided process-oriented feedback. Among 382 …


Life Of Conflict, Joel G. Caroline Oct 2022

Life Of Conflict, Joel G. Caroline

be Still

I am a human being amongst other human being. Together we live in the miracle of nature. Parts of me include philosopher, student, therapist, helper, lover, creator, curious child. Yet I am a human being.


Systematically Higher Ki67 Scores On Core Biopsy Samples Compared To Corresponding Resection Specimen In Breast Cancer: A Multi-Operator And Multi-Institutional Study, Indu Arun, Renaldas Augulis, Sunil S Badve, Yalai Bai, Anita L Bane, John M S Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Henk Buikema, Martin C Chang, Robin L Dietz, Andrew Dodson, Susan Fineberg, Cornelia M Focke, Dongxia Gao, Allen M Gown, Carolina Gutierrez, Johan Hartman, Zuzana Kos, Anne-Vibeke Lænkholm, Arvydas Laurinavicius, Richard M Levenson, Rustin Mahboubi-Ardakani, Mauro G Mastropasqua, Sharon Nofech-Mozes, C Kent Osborne, Frédérique M Penault-Llorca, Tammy Piper, Mary Anne Quintayo, Tilman T Rau, Stefan Reinhard, Stephanie Robertson, Roberto Salgado, Tomoharu Sugie, Bert Van Der Vegt, Giuseppe Viale, Lila A Zabaglo, Daniel F Hayes, Mitch Dowsett, Torsten O Nielsen, David L Rimm, International Ki67 In Breast Cancer Working Group Of The Breast International Group And North American Breast Cancer Group (Big-Nabcg) Oct 2022

Systematically Higher Ki67 Scores On Core Biopsy Samples Compared To Corresponding Resection Specimen In Breast Cancer: A Multi-Operator And Multi-Institutional Study, Indu Arun, Renaldas Augulis, Sunil S Badve, Yalai Bai, Anita L Bane, John M S Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Henk Buikema, Martin C Chang, Robin L Dietz, Andrew Dodson, Susan Fineberg, Cornelia M Focke, Dongxia Gao, Allen M Gown, Carolina Gutierrez, Johan Hartman, Zuzana Kos, Anne-Vibeke Lænkholm, Arvydas Laurinavicius, Richard M Levenson, Rustin Mahboubi-Ardakani, Mauro G Mastropasqua, Sharon Nofech-Mozes, C Kent Osborne, Frédérique M Penault-Llorca, Tammy Piper, Mary Anne Quintayo, Tilman T Rau, Stefan Reinhard, Stephanie Robertson, Roberto Salgado, Tomoharu Sugie, Bert Van Der Vegt, Giuseppe Viale, Lila A Zabaglo, Daniel F Hayes, Mitch Dowsett, Torsten O Nielsen, David L Rimm, International Ki67 In Breast Cancer Working Group Of The Breast International Group And North American Breast Cancer Group (Big-Nabcg)

Faculty, Staff and Students Publications

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut …


Crucial Nuances In Understanding (Mis)Associations Between The Neonatal Microbiome And Cesarean Delivery, Kjersti M Aagaard Oct 2022

Crucial Nuances In Understanding (Mis)Associations Between The Neonatal Microbiome And Cesarean Delivery, Kjersti M Aagaard

Faculty, Staff and Students Publications

As rates of Cesarean delivery and common non-communicable disorders (NCDs), such as obesity, metabolic disease, and atopy/asthma, have concomitantly increased in recent decades, investigators have attempted to discern a causal link. One line of research has led to a hypothesis that Cesarean birth disrupts the presumed normal process of colonization of the neonatal microbiome with vaginal microbes, yielding NCDs later in life. However, a direct link between a disrupted microbiota transfer at time of delivery and acute and/or chronic illness in infants born via Cesarean has not been causally established. Microbiota seeding from maternal vaginal or stool sources has been …