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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
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
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.
Making An Impact On Kidney Disease In People With Type 2 Diabetes: The Importance Of Screening For Albuminuria, Janet B Mcgill, Hermann Haller, Prabir Roy-Chaudhury, Andrea Cherrington, Takashi Wada, Christoph Wanner, Linong Ji, Peter Rossing
Making An Impact On Kidney Disease In People With Type 2 Diabetes: The Importance Of Screening For Albuminuria, Janet B Mcgill, Hermann Haller, Prabir Roy-Chaudhury, Andrea Cherrington, Takashi Wada, Christoph Wanner, Linong Ji, Peter Rossing
Open Access Publications
Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review …
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
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 …
Human Metapneumovirus Phosphoprotein Independently Drives Phase Separation And Recruits Nucleoprotein To Liquid-Like Bodies, Kerri Beth Boggs, Kearstin Edmonds, Nicolas Cifuentes-Munoz, Farah El Najjar, Conny Ossandón, Mckenna Roe, Chao Wu, Carole L Moncman, Trevor P Creamer, Gaya K Amarasinghe, Daisy W Leung, Rebecca Ellis Dutch
Human Metapneumovirus Phosphoprotein Independently Drives Phase Separation And Recruits Nucleoprotein To Liquid-Like Bodies, Kerri Beth Boggs, Kearstin Edmonds, Nicolas Cifuentes-Munoz, Farah El Najjar, Conny Ossandón, Mckenna Roe, Chao Wu, Carole L Moncman, Trevor P Creamer, Gaya K Amarasinghe, Daisy W Leung, Rebecca Ellis Dutch
Open Access Publications
Human metapneumovirus (HMPV) inclusion bodies (IBs) are dynamic structures required for efficient viral replication and transcription. The minimum components needed to form IB-like structures in cells are the nucleoprotein (N) and the tetrameric phosphoprotein (P). HMPV P binds to the following two versions of the N protein in infected cells: N-terminal P residues interact with monomeric N (N
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
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
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
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 …
Dissociation Between Individual Differences In Self-Reported Pain Intensity And Underlying Fmri Brain Activation, M E Hoeppli, H Nahman-Averbuch, W A Hinkle, E Leon, J Peugh, M Lopez-Sola, C D King, K R Goldschneider, R C Coghill
Dissociation Between Individual Differences In Self-Reported Pain Intensity And Underlying Fmri Brain Activation, M E Hoeppli, H Nahman-Averbuch, W A Hinkle, E Leon, J Peugh, M Lopez-Sola, C D King, K R Goldschneider, R C Coghill
Open Access Publications
Pain is an individual experience. Previous studies have highlighted changes in brain activation and morphology associated with within- and interindividual pain perception. In this study we sought to characterize brain mechanisms associated with between-individual differences in pain in a sample of healthy adolescent and adult participants (N = 101). Here we show that pain ratings varied widely across individuals and that individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. Furthermore, brain activation related …
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
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
Differential And Shared Genetic Effects On Kidney Function Between Diabetic And Non-Diabetic Individuals, Thomas W. Winkler, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Michael A. Province, Et Al
Differential And Shared Genetic Effects On Kidney Function Between Diabetic And Non-Diabetic Individuals, Thomas W. Winkler, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Michael A. Province, Et Al
Open Access Publications
No abstract provided.
A Long-Acting Interleukin-7, Rhil-7-Hyfc, Enhances Car T Cell Expansion, Persistence, And Anti-Tumor Activity, Miriam Y Kim, Reyka Jayasinghe, Jessica M Devenport, Julie K Ritchey, Michael P Rettig, Julie O'Neal, Karl W Staser, Krista M Kennerly, Alun J Carter, Feng Gao, Byung Ha Lee, Matthew L Cooper, John F Dipersio
A Long-Acting Interleukin-7, Rhil-7-Hyfc, Enhances Car T Cell Expansion, Persistence, And Anti-Tumor Activity, Miriam Y Kim, Reyka Jayasinghe, Jessica M Devenport, Julie K Ritchey, Michael P Rettig, Julie O'Neal, Karl W Staser, Krista M Kennerly, Alun J Carter, Feng Gao, Byung Ha Lee, Matthew L Cooper, John F Dipersio
Open Access Publications
Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free …
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
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 …
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
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 …
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
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 …
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
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, …
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
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 …
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
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 …
Clonal Dynamics Of Haematopoiesis Across The Human Lifespan, Emily Mitchell, David H Spencer, Et Al
Clonal Dynamics Of Haematopoiesis Across The Human Lifespan, Emily Mitchell, David H Spencer, Et Al
Open Access Publications
Age-related change in human haematopoiesis causes reduced regenerative capacity
Sars-Cov-2 Accessory Proteins Reveal Distinct Serological Signatures In Children, Asmaa Hachim, Gaya K Amarasinghe, Abraham J Qavi, Et Al
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
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. …
Neuronal Hyperexcitability Drives Central And Peripheral Nervous System Tumor Progression In Models Of Neurofibromatosis-1, Corina Anastasaki, Juan Mo, Ji-Kang Chen, Jit Chatterjee, Yuan Pan, Suzanne M Scheaffer, Olivia Cobb, Michelle Monje, Lu Q Le, David H Gutmann
Neuronal Hyperexcitability Drives Central And Peripheral Nervous System Tumor Progression In Models Of Neurofibromatosis-1, Corina Anastasaki, Juan Mo, Ji-Kang Chen, Jit Chatterjee, Yuan Pan, Suzanne M Scheaffer, Olivia Cobb, Michelle Monje, Lu Q Le, David H Gutmann
Open Access Publications
Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop nervous system cancers. We show that central and peripheral nervous system neurons from mice with tumor-causing Nf1 gene mutations exhibit hyperexcitability and increased secretion of activity-dependent tumor-promoting paracrine factors. We discovered a neurofibroma mitogen (COL1A2) produced by peripheral neurons in an activity-regulated manner, which increases NF1-deficient Schwann cell proliferation, establishing that neurofibromas are regulated by neuronal activity. In contrast, mice with the Arg1809Cys Nf1 mutation, found …
An Approach For Evaluating The Effects Of Dietary Fiber Polysaccharides On The Human Gut Microbiome And Plasma Proteome, Omar Delannoy-Bruno, Chandani Desai, Ruteja A Barve, Jiye Cheng, Nathan Han, Stacey Marion, Andrew C Heath, Michael J Barratt, Jeffrey I Gordon, Et Al
An Approach For Evaluating The Effects Of Dietary Fiber Polysaccharides On The Human Gut Microbiome And Plasma Proteome, Omar Delannoy-Bruno, Chandani Desai, Ruteja A Barve, Jiye Cheng, Nathan Han, Stacey Marion, Andrew C Heath, Michael J Barratt, Jeffrey I Gordon, Et Al
Open Access Publications
Increases in snack consumption associated with Westernized lifestyles provide an opportunity to introduce nutritious foods into poor diets. We describe two 10-wk-long open label, single group assignment human studies that measured the effects of two snack prototypes containing fiber preparations from two sustainable and scalable sources; the byproducts remaining after isolation of protein from the endosperm of peas and the vesicular pulp remaining after processing oranges for the manufacture of juices. The normal diets of study participants were supplemented with either a pea- or orange fiber-containing snack. We focused our analysis on quantifying the abundances of genes encoding carbohydrate-active enzymes …
Caveolin-1 Temporal Modulation Enhances Antibody Drug Efficacy In Heterogeneous Gastric Cancer, Patrícia M R Pereira, Komal Mandleywala, Sébastien Monette, Melissa Lumish, Kathryn M Tully, Sandeep Surendra Panikar, Mike Cornejo, Audrey Mauguen, Ashwin Ragupathi, Nai C Keltee, Marissa Mattar, Yelena Y Janjigian, Jason S Lewis
Caveolin-1 Temporal Modulation Enhances Antibody Drug Efficacy In Heterogeneous Gastric Cancer, Patrícia M R Pereira, Komal Mandleywala, Sébastien Monette, Melissa Lumish, Kathryn M Tully, Sandeep Surendra Panikar, Mike Cornejo, Audrey Mauguen, Ashwin Ragupathi, Nai C Keltee, Marissa Mattar, Yelena Y Janjigian, Jason S Lewis
Open Access Publications
Resistance mechanisms and heterogeneity in HER2-positive gastric cancers (GC) limit Trastuzumab benefit in 32% of patients, and other targeted therapies have failed in clinical trials. Using patient samples, patient-derived xenografts (PDXs), partially humanized biological models, and HER2-targeted imaging technologies we demonstrate the role of caveolin-1 (CAV1) as a complementary biomarker in GC selection for Trastuzumab therapy. In retrospective analyses of samples from patients enrolled on Trastuzumab trials, the CAV1-high profile associates with low membrane HER2 density and low patient survival. We show a negative correlation between CAV1 tumoral protein levels - a major protein of cholesterol-rich membrane domains - and …
Digital Mental Health Intervention Plus Usual Care Compared With Usual Care Only And Usual Care Plus In-Person Psychological Counseling For Orthopedic Patients With Symptoms Of Depression Or Anxiety: Cohort Study, Ashwin J Leo, Matthew J Schuelke, Devyani M Hunt, J Philip Miller, Patricia A Areán, Abby L Cheng
Digital Mental Health Intervention Plus Usual Care Compared With Usual Care Only And Usual Care Plus In-Person Psychological Counseling For Orthopedic Patients With Symptoms Of Depression Or Anxiety: Cohort Study, Ashwin J Leo, Matthew J Schuelke, Devyani M Hunt, J Philip Miller, Patricia A Areán, Abby L Cheng
Open Access Publications
BACKGROUND: Depression and anxiety frequently coexist with chronic musculoskeletal pain and can negatively impact patients' responses to standard orthopedic treatments. Nevertheless, mental health is not routinely addressed in the orthopedic care setting. If effective, a digital mental health intervention may be a feasible and scalable method of addressing mental health in an orthopedic setting.
OBJECTIVE: We aimed to compare 2-month changes in mental and physical health between orthopedic patients who received a digital mental health intervention in addition to usual orthopedic care, those who received usual orthopedic care only (without a specific mental health intervention), and those who received in-person …
Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin
Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin
Open Access Publications
Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …
A Novel Methodological Approach To Simultaneously Extract High-Quality Total Rna And Proteins From Cortical And Trabecular Bone, Martina Faraldi, Laura Mangiavini, Caterina Conte, Giuseppe Banfi, Nicola Napoli, Giovanni Lombardi
A Novel Methodological Approach To Simultaneously Extract High-Quality Total Rna And Proteins From Cortical And Trabecular Bone, Martina Faraldi, Laura Mangiavini, Caterina Conte, Giuseppe Banfi, Nicola Napoli, Giovanni Lombardi
Open Access Publications
Molecular differences between cortical and trabecular bone, of relevance to understanding the pathophysiological basis of bone diseases, can be determined only through effective isolation methods for RNA and proteins. Here we present a TRIzol-based method, which combines bone pulverization and homogenization to extract simultaneously total RNA and proteins from human cortical and trabecular bone from the same carrot. RNA integrity and purity were determined as the 260/280 nm and 260/230 nm absorbance ratios and the 28S/18S rRNA ratio. Protein integrity and quality were evaluated by Coomassie blue staining. Reverse transcription quantitative polymerase chain reaction and immunoblotting for bone-specific genes and …
Clinical And Molecular Relevance Of Genetic Variants In The Non-Coding Transcriptome Of Patients With Cytogenetically Normal Acute Myeloid Leukemia, Dimitrios Papaioannou, Geoffrey L. Uy, Et Al
Clinical And Molecular Relevance Of Genetic Variants In The Non-Coding Transcriptome Of Patients With Cytogenetically Normal Acute Myeloid Leukemia, Dimitrios Papaioannou, Geoffrey L. Uy, Et Al
Open Access Publications
Expression levels of long non-coding RNA (lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome. We used available genomic databases and stringent filters to annotate genetic variants unequivocally located in the non-coding transcriptome of AML patients. We detected 981 variants, which are recurrently present in lncRNA that are expressed in leukemic blasts. Among these variants, we identified a cytosine-to-thymidine variant in the lncRNA RP5-1074L1.4 and a cytosine-to-thymidine variant in the lncRNA SNHG15, which independently associated with longer survival of CN-AML patients. The presence of the SNHG15 cytosine-to-thymidine variant was also found to associate with better outcome in an independent dataset of CN-AML patients, despite differences in treatment protocols and RNA sequencing techniques. In order to gain biological insights, we cloned and overexpressed both wild-type and variant versions of the SNHG15 lncRNA. In keeping with its negative prognostic impact, overexpression of the wild-type SNHG15 associated with higher proliferation rate of leukemic blasts when compared with the cytosine-to-thymidine variant. We conclude that recurrent genetic variants of lncRNA that are expressed in the leukemic blasts of CN-AML patients have prognostic and potential biological significance.
Ultrasound-Guided Lumbar Medial Branch Blocks And Intra-Articular Facet Joint Injections: A Systematic Review And Meta-Analysis, Zachary M Ashmore, Michael M Bies, James B Meiling, Rajat N Moman, Leslie C Hassett, Christine L Hunt, Steven P Cohen, W Michael Hooten
Ultrasound-Guided Lumbar Medial Branch Blocks And Intra-Articular Facet Joint Injections: A Systematic Review And Meta-Analysis, Zachary M Ashmore, Michael M Bies, James B Meiling, Rajat N Moman, Leslie C Hassett, Christine L Hunt, Steven P Cohen, W Michael Hooten
Open Access Publications
There is great interest in expanding the use of ultrasound (US), but new challenges exist with its application to lumbar facet-targeted procedures. The primary aim of this systematic review and meta-analysis was to determine the risk of incorrect needle placement associated with US-guided lumbar medial branch blocks (MBB) and facet joint injections (FJI) as confirmed by fluoroscopy or computerized tomography (CT). An a priori protocol was registered, and a database search was conducted. Inclusion criteria included all study types. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials and the National Heart, Lung, …
Outcomes Of Diabetic Ketoacidosis In Adults With End-Stage Kidney Disease: Retrospective Study Based On A National Database, Karthik Gangu, Sanket D. Basida, Anitha Vijayan, Sindhu Avula, Aniesh Bobba
Outcomes Of Diabetic Ketoacidosis In Adults With End-Stage Kidney Disease: Retrospective Study Based On A National Database, Karthik Gangu, Sanket D. Basida, Anitha Vijayan, Sindhu Avula, Aniesh Bobba
Open Access Publications
INTRODUCTION: The prevalence of diabetes mellitus (DM) in the United States has steadily increased over the past few decades. End-stage kidney disease (ESKD) and diabetic ketoacidosis (DKA) are among the most common chronic and acute complications of DM. Guidance on the management of DKA in ESKD is limited by lack of evidence. We investigated the in-hospital outcomes of patients hospitalized for DKA with underlying ESKD. Methods: We carried out a retrospective cohort study and utilized the National Inpatient Sample (NIS) database from 2016 to 2018. International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10 CM) codes were used to identify …
Evaluating The Efficacy Of Rib-To-Pelvis Growth-Friendly Surgery For The Treatment Of Non-Ambulatory Early-Onset Scoliosis Myelomeningocele Patients, Norman Ramirez, Gerardo Olivella, Ryan E Fitzgerald, John T Smith, Peter F Sturm, Paul D Sponseller, Lawrence I Karlin, Scott J Luhmann, Norberto J Torres-Lugo, Tricia St Hilaire, Pediatric Spine Study Group
Evaluating The Efficacy Of Rib-To-Pelvis Growth-Friendly Surgery For The Treatment Of Non-Ambulatory Early-Onset Scoliosis Myelomeningocele Patients, Norman Ramirez, Gerardo Olivella, Ryan E Fitzgerald, John T Smith, Peter F Sturm, Paul D Sponseller, Lawrence I Karlin, Scott J Luhmann, Norberto J Torres-Lugo, Tricia St Hilaire, Pediatric Spine Study Group
Open Access Publications
INTRODUCTION: Early-onset scoliosis (EOS) is a well-known orthopaedic manifestation in patients with myelomeningocele. The rib-based growing system (RBGS) has been proposed as an alternative for these individuals because of the poor outcomes with traditional surgical techniques. We aimed to describe the effect of RBGS in patients with nonambulatory EOS myelomeningocele.
METHODS: We retrospectively reviewed the Pediatric Spine Study Group Multicenter Database for all patients with nonambulatory EOS myelomeningocele treated with RBGS from 2004 to 2019. Demographics, surgical data, radiographic findings, and postoperative complications were obtained. The quality-of-life parameters were assessed postoperatively using the Early-onset Scoliosis Questionnaire-24.
RESULTS: Thirty patients (18 …