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'I Need Time To Start Antiretroviral Therapy': Understanding Reasons For Delayed Art Initiation Among People Diagnosed With Hiv In Lusaka, Zambia, Chanda Mwamba, Laura K Beres, Stephanie M Topp, Njekwa Mukamba, Sandra Simbeza, Kombatende Sikombe, Aaloke Mody, Elvin Geng, Charles B Holmes, Caitlin E Kennedy, Izukanji Sikazwe, Julie A Denison, Carolyn Bolton Moore Dec 2022

'I Need Time To Start Antiretroviral Therapy': Understanding Reasons For Delayed Art Initiation Among People Diagnosed With Hiv In Lusaka, Zambia, Chanda Mwamba, Laura K Beres, Stephanie M Topp, Njekwa Mukamba, Sandra Simbeza, Kombatende Sikombe, Aaloke Mody, Elvin Geng, Charles B Holmes, Caitlin E Kennedy, Izukanji Sikazwe, Julie A Denison, Carolyn Bolton Moore

Open Access Publications

INTRODUCTION: Rapid antiretroviral therapy (ART) initiation can improve patient outcomes such as viral suppression and prevent new infections. However, not everyone who can start ART does so immediately.

METHODS: We conducted a qualitative study to inform interventions supporting rapid initiation in the 'Test and Start' era. We purposively sampled 20 adult patients living with HIV and a previous gap in care from ten health facilities in Lusaka, Zambia for interviews. We inductively analysed transcripts using a thematic, narrative approach. In their narratives, seven participants discussed delaying ART initiation.

RESULTS: Drawing on messages gleaned from facility-based counselling and community information, many …


First-Generation And Continuing-Generation College Graduates' Application, Acceptance, And Matriculation To U.S. Medical Schools: A National Cohort Study, Hyacinth R C Mason, Ashar Ata, Mytien Nguyen, Sunny Nakae, Devasmita Chakraverty, Branden Eggan, Sarah Martinez, Donna B Jeffe Dec 2022

First-Generation And Continuing-Generation College Graduates' Application, Acceptance, And Matriculation To U.S. Medical Schools: A National Cohort Study, Hyacinth R C Mason, Ashar Ata, Mytien Nguyen, Sunny Nakae, Devasmita Chakraverty, Branden Eggan, Sarah Martinez, Donna B Jeffe

Open Access Publications

Many U.S. medical schools conduct holistic review of applicants to enhance the socioeconomic and experiential diversity of the physician workforce. The authors examined the role of first-generation college-graduate status on U.S. medical school application, acceptance, and matriculation, hypothesizing that first-generation (vs. continuing-generation) college graduates would be less likely to apply and gain acceptance to medical school.Secondary analysis of de-identified data from a retrospective national-cohort study was conducted for individuals who completed the 2001-2006 Association of American Medical Colleges (AAMC) Pre-Medical College Admission Test Questionnaire (PMQ) and the Medical College Admissions Test (MCAT). AAMC provided medical school application, acceptance, and matriculation …


The Microbial One-Hit Wonder, Brigida A. Rusconi, Rodney D. Newberry Sep 2022

The Microbial One-Hit Wonder, Brigida A. Rusconi, Rodney D. Newberry

Open Access Publications

Intestinal inflammation, in the absence of infection, occurs from contributions by genetics and environment. Chen et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210324) challenge this concept by demonstrating that a dominant transmissible dysbiotic microbial community predisposes to intestinal inflammation in absence of genetic alterations.


Multisite Learning Of High-Dimensional Heterogeneous Data With Applications To Opioid Use Disorder Study Of 15,000 Patients Across 5 Clinical Sites, Xiaokang Liu, Rui Duan, Chongliang Luo, Alexis Ogdie, Jason H Moore, Henry R Kranzler, Jiang Bian, Yong Chen Jun 2022

Multisite Learning Of High-Dimensional Heterogeneous Data With Applications To Opioid Use Disorder Study Of 15,000 Patients Across 5 Clinical Sites, Xiaokang Liu, Rui Duan, Chongliang Luo, Alexis Ogdie, Jason H Moore, Henry R Kranzler, Jiang Bian, Yong Chen

Open Access Publications

Integrating data across institutions can improve learning efficiency. To integrate data efficiently while protecting privacy, we propose A one-shot, summary-statistics-based, Distributed Algorithm for fitting Penalized (ADAP) regression models across multiple datasets. ADAP utilizes patient-level data from a lead site and incorporates the first-order (ADAP1) and second-order gradients (ADAP2) of the objective function from collaborating sites to construct a surrogate objective function at the lead site, where model fitting is then completed with proper regularizations applied. We evaluate the performance of the proposed method using both simulation and a real-world application to study risk factors for opioid use disorder (OUD) using …


Comparability Of Clinical Trials And Spontaneous Reporting Data Regarding Covid-19 Vaccine Safety, Chongliang Luo, Jingcheng Du, Adam Cuker, Ebbing Lautenbach, David A Asch, Gregory A Poland, Cui Tao, Yong Chen Jun 2022

Comparability Of Clinical Trials And Spontaneous Reporting Data Regarding Covid-19 Vaccine Safety, Chongliang Luo, Jingcheng Du, Adam Cuker, Ebbing Lautenbach, David A Asch, Gregory A Poland, Cui Tao, Yong Chen

Open Access Publications

Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines ("Pfizer" vaccine dose 1 and 2, "Moderna" vaccine dose 1 and 2, and "Janssen" vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports …


Detection Of Bourbon Virus-Specific Serum Neutralizing Antibodies In Human Serum In Missouri, Usa, Gayan Bamunuarachchi, Houda Harastani, Paul W Rothlauf, Ya-Nan Dai, Ali Ellebedy, Daved Fremont, Sean P J Whelan, David Wang, Adrianus C M Boon Jun 2022

Detection Of Bourbon Virus-Specific Serum Neutralizing Antibodies In Human Serum In Missouri, Usa, Gayan Bamunuarachchi, Houda Harastani, Paul W Rothlauf, Ya-Nan Dai, Ali Ellebedy, Daved Fremont, Sean P J Whelan, David Wang, Adrianus C M Boon

Open Access Publications

Bourbon virus (BRBV) was first discovered in 2014 in a fatal human case. Since then it has been detected in the tick Amblyomma americanum in the states of Missouri and Kansas in the United States. Despite the high prevalence of BRBV in ticks in these states, very few human cases have been reported, and the true infection burden of BRBV in the community is unknown. Here, we developed two virus neutralization assays, a vesicular stomatitis virus (VSV)-BRBV pseudotyped rapid assay and a BRBV focus reduction neutralization assay, to assess the seroprevalence of BRBV neutralizing antibodies in human sera collected in …


Paris And Sparta: Finding The Achilles' Heel Of Sars-Cov-2, Viviana Simon, Ali H Ellebedy, Et Al Jun 2022

Paris And Sparta: Finding The Achilles' Heel Of Sars-Cov-2, Viviana Simon, Ali H Ellebedy, Et Al

Open Access Publications

To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators.


Structure Of A Vaccine-Induced, Germline-Encoded Human Antibody Defines A Neutralizing Epitope On The Sars-Cov-2 Spike N-Terminal Domain, Clara G Altomare, Daniel C Adelsberg, Juan Manuel Carreno, Iden A Sapse, Fatima Amanat, Ali H Ellebedy, Viviana Simon, Florian Krammer, Goran Bajic Jun 2022

Structure Of A Vaccine-Induced, Germline-Encoded Human Antibody Defines A Neutralizing Epitope On The Sars-Cov-2 Spike N-Terminal Domain, Clara G Altomare, Daniel C Adelsberg, Juan Manuel Carreno, Iden A Sapse, Fatima Amanat, Ali H Ellebedy, Viviana Simon, Florian Krammer, Goran Bajic

Open Access Publications

Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy …


The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic And Oxidative Stress Responses In Acinetobacter, Anna J Hooppaw, Jenna C Mcguffey, Gisela Di Venanzio, Juan C Ortiz-Marquez, Brent S Weber, Tasia Joy Lightly, Tim Van Opijnen, Nichollas E Scott, Silvia T Cardona, Mario F Feldman Jun 2022

The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic And Oxidative Stress Responses In Acinetobacter, Anna J Hooppaw, Jenna C Mcguffey, Gisela Di Venanzio, Juan C Ortiz-Marquez, Brent S Weber, Tasia Joy Lightly, Tim Van Opijnen, Nichollas E Scott, Silvia T Cardona, Mario F Feldman

Open Access Publications

The opportunistic pathogen Acinetobacter baumannii is responsible for a wide range of infections that are becoming increasingly difficult to treat due to extremely high rates of multidrug resistance. Acinetobacter's pathogenic potential is thought to rely on a "persist and resist" strategy that facilitates its remarkable ability to survive under a variety of harsh conditions. The


Isolation Of A Potently Neutralizing And Protective Human Monoclonal Antibody Targeting Yellow Fever Virus, Michael P Doyle, Joseph R Genualdi, Adam L Bailey, Nurgun Kose, Christopher Gainza, Jessica Rodriguez, Kristen M Reeder, Christopher A Nelson, Prashant N Jethva, Rachel E Sutton, Robin G Bombardi, Michael L Gross, Justin G Julander, Daved H Fremont, Michael S Diamond, James E Crowe Jun 2022

Isolation Of A Potently Neutralizing And Protective Human Monoclonal Antibody Targeting Yellow Fever Virus, Michael P Doyle, Joseph R Genualdi, Adam L Bailey, Nurgun Kose, Christopher Gainza, Jessica Rodriguez, Kristen M Reeder, Christopher A Nelson, Prashant N Jethva, Rachel E Sutton, Robin G Bombardi, Michael L Gross, Justin G Julander, Daved H Fremont, Michael S Diamond, James E Crowe

Open Access Publications

Yellow fever virus (YFV) causes sporadic outbreaks of infection in South America and sub-Saharan Africa. While live-attenuated yellow fever virus vaccines based on three substrains of 17D are considered some of the most effective vaccines in use, problems with production and distribution have created large populations of unvaccinated, vulnerable individuals in areas of endemicity. To date, specific antiviral therapeutics have not been licensed for human use against YFV or any other related flavivirus. Recent advances in monoclonal antibody (mAb) technology have allowed the identification of numerous candidate therapeutics targeting highly pathogenic viruses, including many flaviviruses. Here, we sought to identify …


Cancer Cells Dying From Ferroptosis Impede Dendritic Cell-Mediated Anti-Tumor Immunity, Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S Ravichandran, Peter Vandenabeele Jun 2022

Cancer Cells Dying From Ferroptosis Impede Dendritic Cell-Mediated Anti-Tumor Immunity, Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S Ravichandran, Peter Vandenabeele

Open Access Publications

Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model of ferroptosis, distinguishing three phases in the process-'initial' associated with lipid peroxidation, 'intermediate' correlated with ATP release and 'terminal' recognized by HMGB1 release and loss of plasma membrane integrity-that serves as tool to study immune cell responses to ferroptotic cancer cells. Co-culturing ferroptotic cancer cells with dendritic cells (DC), reveals …


The Challenges Of Interrogating Adipose Tissue Extracellular Vesicle Functions In Physiology, Clair Crewe Jun 2022

The Challenges Of Interrogating Adipose Tissue Extracellular Vesicle Functions In Physiology, Clair Crewe

Open Access Publications

No abstract provided.


68ga-Labeled Benzothiazole Derivatives For Imaging Aβ Plaques In Cerebral Amyloid Angiopathy, Truc T Huynh, Yujue Wang, Karna Terpstra, Hong-Jun Cho, Liviu M Mirica, Buck E Rogers Jun 2022

68ga-Labeled Benzothiazole Derivatives For Imaging Aβ Plaques In Cerebral Amyloid Angiopathy, Truc T Huynh, Yujue Wang, Karna Terpstra, Hong-Jun Cho, Liviu M Mirica, Buck E Rogers

Open Access Publications

Timely diagnostic imaging plays a crucial role in managing cerebral amyloid angiopathy (CAA)-the condition in which amyloid β is deposited on blood vessels. To selectively map these amyloid plaques, we have designed amyloid-targeting ligands that can effectively complex with


Antigen Glycosylation Regulates Efficacy Of Car T Cells Targeting Cd19, Amanda Heard, Jack H Landmann, Ava R Hansen, Yu-Sung Hsu, Mehmet Emrah Selli, John M Warrington, John Lattin, Jufang Chang, Helen Ha, Balraj Doray, Abby M Green, Nathan Singh, Et Al Jun 2022

Antigen Glycosylation Regulates Efficacy Of Car T Cells Targeting Cd19, Amanda Heard, Jack H Landmann, Ava R Hansen, Yu-Sung Hsu, Mehmet Emrah Selli, John M Warrington, John Lattin, Jufang Chang, Helen Ha, Balraj Doray, Abby M Green, Nathan Singh, Et Al

Open Access Publications

While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most patients treated will not achieve durable remission. Identification of the mechanisms leading to failure is essential to broadening the efficacy of this promising platform. Several studies have demonstrated that disruption of CD19 genes and transcripts can lead to disease relapse after initial response; however, few other tumor-intrinsic drivers of CAR T cell failure have been reported. Here we identify expression of the Golgi-resident intramembrane protease Signal peptide peptidase-like 3 (SPPL3) in malignant B cells as a potent regulator of resistance …


Phase I Study Of Safety, Tolerability, And Efficacy Of Tebentafusp Using A Step-Up Dosing Regimen And Expansion In Patients With Metastatic Uveal Melanoma, Richard D Carvajal, Paul Nathan, Joseph J Sacco, Marlana Orloff, Leonel F Hernandez-Aya, Jessica Yang, Jason J Luke, Marcus O Butler, Sarah Stanhope, Laura Collins, Cheryl Mcalpine, Chris Holland, Shaad E Abdullah, Takami Sato Jun 2022

Phase I Study Of Safety, Tolerability, And Efficacy Of Tebentafusp Using A Step-Up Dosing Regimen And Expansion In Patients With Metastatic Uveal Melanoma, Richard D Carvajal, Paul Nathan, Joseph J Sacco, Marlana Orloff, Leonel F Hernandez-Aya, Jessica Yang, Jason J Luke, Marcus O Butler, Sarah Stanhope, Laura Collins, Cheryl Mcalpine, Chris Holland, Shaad E Abdullah, Takami Sato

Open Access Publications

PURPOSE: This phase I study aimed to define the recommended phase II dose (RP2D) of tebentafusp, a first-in-class T-cell receptor/anti-CD3 bispecific protein, using a three-week step-up dosing regimen, and to assess its safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity in patients with metastatic uveal melanoma (mUM).

METHODS: In this open-label, international, phase I/II study, HLA-A*02 or HLA-A*02:01+ patients with mUM received tebentafusp 20 μg once in week 1 and 30 μg once in week 2. Dose escalation (starting at 54 μg) began at week 3 in a standard 3 + 3 design to define RP2D. Expansion-phase patients were treated at …


Political Environment And Mortality Rates In The United States, 2001-19: Population Based Cross Sectional Analysis, Haider J Warraich, Pankaj Kumar, Khurram Nasir, Karen E Joynt Maddox, Rishi K Wadhera Jun 2022

Political Environment And Mortality Rates In The United States, 2001-19: Population Based Cross Sectional Analysis, Haider J Warraich, Pankaj Kumar, Khurram Nasir, Karen E Joynt Maddox, Rishi K Wadhera

Open Access Publications

OBJECTIVE: To assess recent trends in age adjusted mortality rates (AAMRs) in the United States based on county level presidential voting patterns.

DESIGN: Cross sectional study.

SETTING: USA, 2001-19.

PARTICIPANTS: 99.8% of the US population.

MAIN OUTCOME MEASURES: AAMR per 100 000 population and average annual percentage change (APC).

METHODS: The Centers for Disease Control and Prevention WONDER database was linked to county level data on US presidential elections. County political environment was classified as either Democratic or Republican for the four years that followed a November presidential election. Additional sensitivity analyses analyzed AAMR trends for counties that voted only …


The Aryl Hydrocarbon Receptor Instructs The Immunomodulatory Profile Of A Subset Of Clec4a4, Wei-Le Wang, Jun Kasamatsu, Satoru Joshita, Susan Gilfillan, Blanda Di Luccia, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Jennifer K Bando, Stanley Ching-Cheng Huang, Kentaro Yomogida, Steven J Van Dyken, Marina Cella, Marco Colonna, Et Al Jun 2022

The Aryl Hydrocarbon Receptor Instructs The Immunomodulatory Profile Of A Subset Of Clec4a4, Wei-Le Wang, Jun Kasamatsu, Satoru Joshita, Susan Gilfillan, Blanda Di Luccia, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Jennifer K Bando, Stanley Ching-Cheng Huang, Kentaro Yomogida, Steven J Van Dyken, Marina Cella, Marco Colonna, Et Al

Open Access Publications

SignificanceEosinophils contribute to type 2 immunity against helminths and allergens. The small intestine harbors eosinophils with incompletely understood pathophysiological roles. Here, we show that intestinal eosinophils include two subsets. One expresses the inhibitory receptor Clec4a4 and the inhibitory ligand PD-L1 and is unique to the small intestine; the other manifests a proinflammatory phenotype. Both subsets are blood derived. Remarkably, Clec4a4


Raising Is A High-Performance Method For Identifying Random Transgene Integration Sites, Yusaku Wada, Ariella L G Coler-Reilly, Et Al Jun 2022

Raising Is A High-Performance Method For Identifying Random Transgene Integration Sites, Yusaku Wada, Ariella L G Coler-Reilly, Et Al

Open Access Publications

Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking clonality via the detection of transgene integration sites. RAISING (Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination) is a sensitive, inexpensive alternative to established methods. Its compatibility with Sanger sequencing combined with our CLOVA (Clonality Value) software is critical for those without access to expensive high throughput sequencing. We analyzed samples from 688 individuals infected with the retrovirus HTLV-1, which causes …


Evolutionarily Stable Gene Clusters Shed Light On The Common Grounds Of Pathogenicity In The Acinetobacter Calcoaceticus-Baumannii Complex, Bardya Djahanschiri, Gisela Di Venanzio, Jesus S. Distel, Jennifer Breisch, Marius Alfred Dieckmann, Alexander Goesmann, Beate Averhoff, Stephan Göttig, Gottfried Wilharm, Mario F. Feldman, Ingo Ebersberger Jun 2022

Evolutionarily Stable Gene Clusters Shed Light On The Common Grounds Of Pathogenicity In The Acinetobacter Calcoaceticus-Baumannii Complex, Bardya Djahanschiri, Gisela Di Venanzio, Jesus S. Distel, Jennifer Breisch, Marius Alfred Dieckmann, Alexander Goesmann, Beate Averhoff, Stephan Göttig, Gottfried Wilharm, Mario F. Feldman, Ingo Ebersberger

Open Access Publications

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes independent of their organization in functional gene clusters. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and microsynteny conservation analyses. We delineate gene clusters in …


Peripheral Monocyte-Derived Cells Counter Amyloid Plaque Pathogenesis In A Mouse Model Of Alzheimer's Disease, Ping Yan, Ki-Wook Kim, Qingli Xiao, Xiucui Ma, Leah R. Czerniewski, Haiyan Liu, David R. Rawnsley, Yan Yan, Gwendalyn J. Randolph, Slava Epelman, Jin-Moo Lee, Abhinav Diwan Jun 2022

Peripheral Monocyte-Derived Cells Counter Amyloid Plaque Pathogenesis In A Mouse Model Of Alzheimer's Disease, Ping Yan, Ki-Wook Kim, Qingli Xiao, Xiucui Ma, Leah R. Czerniewski, Haiyan Liu, David R. Rawnsley, Yan Yan, Gwendalyn J. Randolph, Slava Epelman, Jin-Moo Lee, Abhinav Diwan

Open Access Publications

Microglia, the parenchymal tissue macrophages in the brain, surround amyloid plaques in brains of individuals with Alzheimer's disease (AD) but are ineffective at clearing amyloid to mitigate disease progression. Recent studies in mice indicate that microglia are derived exclusively from primitive yolk sac hematopoiesis and self-renew without contribution from ontogenically distinct monocytes/macrophages of definitive adult hematopoietic origin. Using a genetic fate-mapping approach to label cells of definitive hematopoietic origin throughout life span, we discovered that circulating monocytes contribute 6% of plaque-associated macrophages in aged AD mice. Moreover, peripheral monocytes contributed to a higher fraction of macrophages in the choroid plexus, …


A Guide For Managing Patients With Stage I Nsclc: Deciding Between Lobectomy, Segmentectomy, Wedge, Sbrt And Ablation-Part 1: A Guide To Decision-Making, Frank C. Detterbeck, Justin D. Blasberg, Gavitt A. Woodard, Roy H. Decker, Ulas Kumbasar, Henry S. Park, Vincent J. Mase Jr, Brett C. Bade, Andrew X. Li, Whitney S. Brandt, David C. Madoff Jun 2022

A Guide For Managing Patients With Stage I Nsclc: Deciding Between Lobectomy, Segmentectomy, Wedge, Sbrt And Ablation-Part 1: A Guide To Decision-Making, Frank C. Detterbeck, Justin D. Blasberg, Gavitt A. Woodard, Roy H. Decker, Ulas Kumbasar, Henry S. Park, Vincent J. Mase Jr, Brett C. Bade, Andrew X. Li, Whitney S. Brandt, David C. Madoff

Open Access Publications

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, Stereotactic Body Radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making.

Methods: Based on a systematic review from 2000-2021, evidence regarding relevant outcomes was assembled, with attention to …


An Antibody Targeting The N-Terminal Domain Of Sars-Cov-2 Disrupts The Spike Trimer, Naveenchandra Suryadevara, Laura A. Vanblargan, Rita E. Chen, James Brett Case, Michael S. Diamond, Et Al Jun 2022

An Antibody Targeting The N-Terminal Domain Of Sars-Cov-2 Disrupts The Spike Trimer, Naveenchandra Suryadevara, Laura A. Vanblargan, Rita E. Chen, James Brett Case, Michael S. Diamond, Et Al

Open Access Publications

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope ("supersite") on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2-neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, …


Mapping The Lay Of The Land: Using Interactive Network Analytic Tools For Collaboration In Rural Cancer Prevention And Control, Bobbi J Carothers, Peg Allen, Callie Walsh-Bailey, Dixie Duncan, Rebeca Vanderburg Pacheco, Karen R White, Debra Jeckstadt, Edward Tsai, Ross C Brownson Jun 2022

Mapping The Lay Of The Land: Using Interactive Network Analytic Tools For Collaboration In Rural Cancer Prevention And Control, Bobbi J Carothers, Peg Allen, Callie Walsh-Bailey, Dixie Duncan, Rebeca Vanderburg Pacheco, Karen R White, Debra Jeckstadt, Edward Tsai, Ross C Brownson

Open Access Publications

BACKGROUND: Cancer mortality rates in the United States are higher in rural than urban areas, especially for colorectal cancer. Modifiable cancer risks (e.g., tobacco use, obesity) are more prevalent among U.S. rural than urban residents. Social network analyses are common, yet rural informal collaborative networks for cancer prevention and control and practitioner uses of network findings are less well understood.

METHODS: In five service areas in rural Missouri and Illinois, we conducted a network survey of informal multisector networks among agencies that address cancer risk (N = 152 individuals). The survey asked about contact, collaborative activities, and referrals. We calculated …


Changes In Dynamic Postural Stability After Acl Reconstruction: Results Over 2 Years Of Follow-Up, Robert H Brophy, Kevin A Schafer, Derrick M Knapik, John Motley, Amanda Haas, Matthew J Matava, Rick W Wright, Matthew V Smith Jun 2022

Changes In Dynamic Postural Stability After Acl Reconstruction: Results Over 2 Years Of Follow-Up, Robert H Brophy, Kevin A Schafer, Derrick M Knapik, John Motley, Amanda Haas, Matthew J Matava, Rick W Wright, Matthew V Smith

Open Access Publications

Background: The anterior cruciate ligament (ACL) is crucial for knee proprioception and postural stability. While ACL reconstruction (ACLR) and rehabilitation improve postural stability, the timing in improvement of dynamic postural stability after ACLR remains relatively unknown.

Purpose: To evaluate changes in dynamic postural stability after ACLR out to 24 months postoperatively.

Study Design: Case series; Level of evidence, 4.

Methods: Patients undergoing ACLR were prospectively enrolled, and dynamic postural stability was assessed within 2 days before surgery, at 3-month intervals postoperatively to 18 months, then at 24 months. Measurements were made on a multidirectional platform tracking the patient's center of …


Synthetic Gene Circuits For Preventing Disruption Of The Circadian Clock Due To Interleukin-1-Induced Inflammation, Lara Pferdehirt, Anna R Damato, Michal Dudek, Qing-Jun Meng, Erik D Herzog, Farshid Guilak May 2022

Synthetic Gene Circuits For Preventing Disruption Of The Circadian Clock Due To Interleukin-1-Induced Inflammation, Lara Pferdehirt, Anna R Damato, Michal Dudek, Qing-Jun Meng, Erik D Herzog, Farshid Guilak

Open Access Publications

The circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 …


Sars-Cov-2 Accessory Proteins Reveal Distinct Serological Signatures In Children, Asmaa Hachim, Gaya K Amarasinghe, Abraham J Qavi, Et Al May 2022

Sars-Cov-2 Accessory Proteins Reveal Distinct Serological Signatures In Children, Asmaa Hachim, Gaya K Amarasinghe, Abraham J Qavi, Et Al

Open Access Publications

The antibody response magnitude and kinetics may impact clinical severity, serological diagnosis and long-term protection of COVID-19, which may play a role in why children experience lower morbidity. We therefore tested samples from 122 children in Hong Kong with symptomatic (n = 78) and asymptomatic (n = 44) SARS-CoV-2 infections up to 200 days post infection, relative to 71 infected adults (symptomatic n = 61, and asymptomatic n = 10), and negative controls (n = 48). We assessed serum IgG antibodies to a 14-wide antigen panel of structural and accessory proteins by Luciferase Immuno-Precipitation System (LIPS) assay and circulating cytokines. …


Multivalent Designed Proteins Neutralize Sars-Cov-2 Variants Of Concern And Confer Protection Against Infection In Mice, Andrew C Hunt, James Brett Case, Rita E Chen, Baoling Ying, Adam L Bailey, Natasha M Kafai, Michael S Diamond, Et Al May 2022

Multivalent Designed Proteins Neutralize Sars-Cov-2 Variants Of Concern And Confer Protection Against Infection In Mice, Andrew C Hunt, James Brett Case, Rita E Chen, Baoling Ying, Adam L Bailey, Natasha M Kafai, Michael S Diamond, Et Al

Open Access Publications

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. …


Estrogen Metabolites Increase Nociceptor Hyperactivity In A Mouse Model Of Uterine Pain, Zili Xie, Jing Feng, Tao Cai, Ronald Mccarthy, Yuhui Wang, Yonghui Zhao, Zhihua Yi, Kaikai Zang, Yi Yuan, Xueming Hu, Fengxian Li, Qin Liu, Sarah K. England, Hongzhen Hu, Et Al May 2022

Estrogen Metabolites Increase Nociceptor Hyperactivity In A Mouse Model Of Uterine Pain, Zili Xie, Jing Feng, Tao Cai, Ronald Mccarthy, Yuhui Wang, Yonghui Zhao, Zhihua Yi, Kaikai Zang, Yi Yuan, Xueming Hu, Fengxian Li, Qin Liu, Sarah K. England, Hongzhen Hu, Et Al

Open Access Publications

Pain emanating from the female reproductive tract is notoriously difficult to treat, and the prevalence of transient pelvic pain has been placed as high as 70%-80% in women surveyed. Although sex hormones, especially estrogen, are thought to underlie enhanced pain perception in females, the underlying molecular and cellular mechanisms are not completely understood. Here, we showed that the pain-initiating TRPA1 channel was required for pain-related behaviors in a mouse model of estrogen-induced uterine pain in ovariectomized female mice. Surprisingly, 2- and 4-hydroxylated estrogen metabolites (2- and 4-HEMs) in the estrogen hydroxylation pathway, but not estrone, estradiol, or 16-HEMs, directly increased …


Strategies To Achieve Breast Health Equity In The St. Louis Region And Beyond Over 15+ Years, Bettina Drake, Aimee James, Heidi Miller, Akila Anandarajah, Kia L Davis, Sheryll Jackson, Graham A Colditz, Vetta Sanders Thompson May 2022

Strategies To Achieve Breast Health Equity In The St. Louis Region And Beyond Over 15+ Years, Bettina Drake, Aimee James, Heidi Miller, Akila Anandarajah, Kia L Davis, Sheryll Jackson, Graham A Colditz, Vetta Sanders Thompson

Open Access Publications

Community-based participatory strategies are a promising approach to addressing disparities in community health outcomes. This paper details the efforts of Siteman Cancer Center to achieve breast health equity over the past 15+ years. We begin by describing the activities and successes arising from our breast health community partnerships including identifying priorities, developing recommendations, and implementing patient navigation services to advance breast health. This system-wide coordinated navigation approach that includes primary and specialty care providers helped to increase potential impact on reducing breast health disparities by expediting care, increasing care efficiency, and standardizing referral procedures across systems for all women including …


Ceftriaxone Resistance And Adequacy Of Initial Antibiotic Therapy In Community Onset Bacterial Pneumonia, Richard F Van Besien, Nicholas Hampton, Scott T Micek, Marin H Kollef May 2022

Ceftriaxone Resistance And Adequacy Of Initial Antibiotic Therapy In Community Onset Bacterial Pneumonia, Richard F Van Besien, Nicholas Hampton, Scott T Micek, Marin H Kollef

Open Access Publications

ABSTRACT: Much remains unknown about the impact of initial antibiotic adequacy on mortality in community onset bacterial pneumonia (COBP). Therefore, we performed a study to determine how the adequacy of initial antibiotic therapy affects in-hospital mortality for patients with COBP.We carried out a retrospective cohort study among the 11 BJC Healthcare community and academic hospitals in Missouri and Illinois. The electronic medical records for BJC Healthcare were queried to obtain a set of patient admissions with culture positive (respiratory or blood) COBP admitted from January 1, 2016 through December 31, 2019. Patients with COBP required an International Classification of Diseases …