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Full-Text Articles in Medicine and Health Sciences
Genetic Modifiers Of Mendelian Monogenic Collagen Iv Nephropathies In Humans And Mice, Constantinos Deltas, Gregory Papagregoriou, Stavroula F Louka, Apostolos Malatras, Frances Flinter, Daniel P Gale, Susie Gear, Oliver Gross, Julia Hoefele, Rachel Lennon, Jeffrey H Miner, Alessandra Renieri, Judy Savige, A Neil Turner
Genetic Modifiers Of Mendelian Monogenic Collagen Iv Nephropathies In Humans And Mice, Constantinos Deltas, Gregory Papagregoriou, Stavroula F Louka, Apostolos Malatras, Frances Flinter, Daniel P Gale, Susie Gear, Oliver Gross, Julia Hoefele, Rachel Lennon, Jeffrey H Miner, Alessandra Renieri, Judy Savige, A Neil Turner
2020-Current year OA Pubs
Familial hematuria is a clinical sign of a genetically heterogeneous group of conditions, accompanied by broad inter- and intrafamilial variable expressivity. The most frequent condition is caused by pathogenic (or likely pathogenic) variants in the collagen-IV genes,
Sustainable Development For Mobile Health Apps Using The Human-Centered Design Process, Qingfan An, Marjorie M Kelley, Audra Hanners, Po-Yin Yen
Sustainable Development For Mobile Health Apps Using The Human-Centered Design Process, Qingfan An, Marjorie M Kelley, Audra Hanners, Po-Yin Yen
2020-Current year OA Pubs
Well-documented scientific evidence indicates that mobile health (mHealth) apps can improve the quality of life, relieve symptoms, and restore health for patients. In addition to improving patients' health outcomes, mHealth apps reduce health care use and the cost burdens associated with disease management. Currently, patients and health care providers have a wide variety of choices among commercially available mHealth apps. However, due to the high resource costs and low user adoption of mHealth apps, the cost-benefit relationship remains controversial. When compared to traditional expert-driven approaches, applying human-centered design (HCD) may result in more useable, acceptable, and effective mHealth apps. In …
Rapid Direct Detection Of Sars-Cov-2 Aerosols In Exhaled Breath At The Point Of Care, Dishit P Ghumra, Nishit Shetty, Kevin R Mcbrearty, Joseph V Puthussery, Benjamin J Sumlin, Woodrow D Gardiner, Brookelyn M Doherty, Jordan P Magrecki, Jane A O'Halloran, Rachel M Presti, Traci L Bricker, Adrianus C M Boon, Carla M Yuede, John R Cirrito, Rajan K Chakrabarty, Et Al.
Rapid Direct Detection Of Sars-Cov-2 Aerosols In Exhaled Breath At The Point Of Care, Dishit P Ghumra, Nishit Shetty, Kevin R Mcbrearty, Joseph V Puthussery, Benjamin J Sumlin, Woodrow D Gardiner, Brookelyn M Doherty, Jordan P Magrecki, Jane A O'Halloran, Rachel M Presti, Traci L Bricker, Adrianus C M Boon, Carla M Yuede, John R Cirrito, Rajan K Chakrabarty, Et Al.
2020-Current year OA Pubs
Airborne transmission via virus-laden aerosols is a dominant route for the transmission of respiratory diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Direct, non-invasive screening of respiratory virus aerosols in patients has been a long-standing technical challenge. Here, we introduce a point-of-care testing platform that directly detects SARS-CoV-2 aerosols in as little as two exhaled breaths of patients and provides results in under 60 s. It integrates a hand-held breath aerosol collector and a llama-derived, SARS-CoV-2 spike-protein specific nanobody bound to an ultrasensitive micro-immunoelectrode biosensor, which detects the oxidation of tyrosine amino acids present in SARS-CoV-2 viral particles. Laboratory …
Microglial Rev-Erbα Regulates Inflammation And Lipid Droplet Formation To Drive Tauopathy In Male Mice, Jiyeon Lee, Julie M Dimitry, Jong Hee Song, Minsoo Son, Patrick W Sheehan, Melvin W King, G Travis Tabor, Young Ah Goo, Mitchell A Lazar, Leonard Petrucelli, Erik S Musiek
Microglial Rev-Erbα Regulates Inflammation And Lipid Droplet Formation To Drive Tauopathy In Male Mice, Jiyeon Lee, Julie M Dimitry, Jong Hee Song, Minsoo Son, Patrick W Sheehan, Melvin W King, G Travis Tabor, Young Ah Goo, Mitchell A Lazar, Leonard Petrucelli, Erik S Musiek
2020-Current year OA Pubs
Alzheimer's disease, the most common age-related neurodegenerative disease, is characterized by tau aggregation and associated with disrupted circadian rhythms and dampened clock gene expression. REV-ERBα is a core circadian clock protein which also serves as a nuclear receptor and transcriptional repressor involved in lipid metabolism and macrophage function. Global REV-ERBα deletion has been shown to promote microglial activation and mitigate amyloid plaque formation. However, the cell-autonomous effects of microglial REV-ERBα in healthy brain and in tauopathy are unexplored. Here, we show that microglial REV-ERBα deletion enhances inflammatory signaling, disrupts lipid metabolism, and causes lipid droplet (LD) accumulation specifically in male …
Design, Synthesis, And Evaluation Of Novel Δ2‑Thiazolino2‑Pyridone Derivatives That Potentiate Isoniazid Activity In An Isoniazid-Resistant Mycobacterium Tuberculosis Mutant, Souvik Sarkar, Anne E. Mayer Bridwell, Erin R. Wang, Samuel R. Mckee, Joy Valenta, Gregory A. Harrison, Kelly N. Flentie, Frederick L. Henry, Christina L. Stallings, Et Al.
Design, Synthesis, And Evaluation Of Novel Δ2‑Thiazolino2‑Pyridone Derivatives That Potentiate Isoniazid Activity In An Isoniazid-Resistant Mycobacterium Tuberculosis Mutant, Souvik Sarkar, Anne E. Mayer Bridwell, Erin R. Wang, Samuel R. Mckee, Joy Valenta, Gregory A. Harrison, Kelly N. Flentie, Frederick L. Henry, Christina L. Stallings, Et Al.
2020-Current year OA Pubs
No abstract provided.
Prevalence And Trends Of Advanced Hiv Disease Among Antiretroviral Therapy-Naïve And Antiretroviral Therapy-Experienced Patients In South Africa Between 2010-2021: A Systematic Review And Meta-Analysis, Marcel K Kitenge, Geoffrey Fatti, Ingrid Eshun-Wilson, Omololu Aluko, Peter Nyasulu
Prevalence And Trends Of Advanced Hiv Disease Among Antiretroviral Therapy-Naïve And Antiretroviral Therapy-Experienced Patients In South Africa Between 2010-2021: A Systematic Review And Meta-Analysis, Marcel K Kitenge, Geoffrey Fatti, Ingrid Eshun-Wilson, Omololu Aluko, Peter Nyasulu
2020-Current year OA Pubs
BACKGROUND: Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022.
METHODS: We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the …
Efficacy Of Checkpoint Inhibition After Car-T Failure In Aggressive B-Cell Lymphomas: Outcomes From 15 Us Institutions, Ajay Major, Michael J Slade, Nathan Singh, Et Al.
Efficacy Of Checkpoint Inhibition After Car-T Failure In Aggressive B-Cell Lymphomas: Outcomes From 15 Us Institutions, Ajay Major, Michael J Slade, Nathan Singh, Et Al.
2020-Current year OA Pubs
Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate …
Genomic Landscape Of Tp53-Mutated Myeloid Malignancies, Haley J Abel, Karolyn A Oetjen, Christopher A Miller, Sai M Ramakrishnan, Ryan B Day, Nichole M Helton, Catrina C Fronick, Robert S Fulton, Sharon E Heath, Stefan P Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J Duncavage, Molly C Schroeder, Jacqueline E Payton, David H Spencer, Matthew J Walter, Peter Westervelt, John F Dipersio, Timothy J Ley, Daniel C Link
Genomic Landscape Of Tp53-Mutated Myeloid Malignancies, Haley J Abel, Karolyn A Oetjen, Christopher A Miller, Sai M Ramakrishnan, Ryan B Day, Nichole M Helton, Catrina C Fronick, Robert S Fulton, Sharon E Heath, Stefan P Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J Duncavage, Molly C Schroeder, Jacqueline E Payton, David H Spencer, Matthew J Walter, Peter Westervelt, John F Dipersio, Timothy J Ley, Daniel C Link
2020-Current year OA Pubs
TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants, which complicates detailed genomic analysis by conventional clinical techniques. We performed whole-genome sequencing (WGS) of 42 acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) cases with paired normal tissue to better characterize the genomic landscape of TP53-mutated AML/MDS. WGS accurately determines TP53 allele status, a key prognostic factor, resulting in the reclassification of 12% of cases from monoallelic to multihit. Although aneuploidy and chromothripsis are shared with most TP53-mutated cancers, the specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin. ETV6 expression …
The Proteome Of Extracellular Vesicles Of The Lung Fluke Paragonimus Kellicotti Produced In Vitro And In The Lung Cyst, Lucia S Di Maggio, Kerstin Fischer, Devyn Yates, Kurt C Curtis, Bruce A Rosa, John Martin, Petra Erdmann-Gilmore, Robert S W Sprung, Makedonka Mitreva, R Reid Townsend, Gary J Weil, Peter U Fischer
The Proteome Of Extracellular Vesicles Of The Lung Fluke Paragonimus Kellicotti Produced In Vitro And In The Lung Cyst, Lucia S Di Maggio, Kerstin Fischer, Devyn Yates, Kurt C Curtis, Bruce A Rosa, John Martin, Petra Erdmann-Gilmore, Robert S W Sprung, Makedonka Mitreva, R Reid Townsend, Gary J Weil, Peter U Fischer
2020-Current year OA Pubs
Paragonimiasis is a zoonotic, food-borne trematode infection that affects 21 million people globally. Trematodes interact with their hosts via extracellular vesicles (EV) that carry protein and RNA cargo. We analyzed EV in excretory-secretory products (ESP) released by Paragonimus kellicotti adult worms cultured in vitro (EV ESP) and EV isolated from lung cyst fluid (EV CFP) recovered from infected gerbils. The majority of EV were approximately 30-50 nm in diameter. We identified 548 P. kellicotti-derived proteins in EV ESP by mass spectrometry and 8 proteins in EV CFP of which 7 were also present in EV ESP. No parasite-derived proteins were …
Interpreting The Mechanism Of Synergism For Drug Combinations Using Attention-Based Hierarchical Graph Pooling, Zehao Dong, Heming Zhang, Yixin Chen, Philip R O Payne, Fuhai Li
Interpreting The Mechanism Of Synergism For Drug Combinations Using Attention-Based Hierarchical Graph Pooling, Zehao Dong, Heming Zhang, Yixin Chen, Philip R O Payne, Fuhai Li
2020-Current year OA Pubs
Synergistic drug combinations provide huge potentials to enhance therapeutic efficacy and to reduce adverse reactions. However, effective and synergistic drug combination prediction remains an open question because of the unknown causal disease signaling pathways. Though various deep learning (AI) models have been proposed to quantitatively predict the synergism of drug combinations, the major limitation of existing deep learning methods is that they are inherently not interpretable, which makes the conclusions of AI models untransparent to human experts, henceforth limiting the robustness of the model conclusion and the implementation ability of these models in real-world human-AI healthcare. In this paper, we …
Changing Severity And Epidemiology Of Adults Hospitalized With Coronavirus Disease 2019 (Covid-19) In The United States After Introduction Of Covid-19 Vaccines, March 2021-August 2022, Noah Kojima, Jennie H Kwon, Et Al.
Changing Severity And Epidemiology Of Adults Hospitalized With Coronavirus Disease 2019 (Covid-19) In The United States After Introduction Of Covid-19 Vaccines, March 2021-August 2022, Noah Kojima, Jennie H Kwon, Et Al.
2020-Current year OA Pubs
INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies.
METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed.
RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), …
Risk Of Autism Spectrum Disorder And Association Of Its Symptoms With Psychiatric And Substance Use Disorders In Non-Clinical Student Sample In Kenya: Cross-Sectional Study, Victoria N Mutiso, David M Ndetei, Esther N Muia, Monicah Masake, Rita K Alietsi, Lydia Onsinyo, Christine Musyimi, Daniel Mamah
Risk Of Autism Spectrum Disorder And Association Of Its Symptoms With Psychiatric And Substance Use Disorders In Non-Clinical Student Sample In Kenya: Cross-Sectional Study, Victoria N Mutiso, David M Ndetei, Esther N Muia, Monicah Masake, Rita K Alietsi, Lydia Onsinyo, Christine Musyimi, Daniel Mamah
2020-Current year OA Pubs
BACKGROUND: The prevalence and patterns of autism spectrum disorder (ASD) symptoms/traits and the associations of ASD with psychiatric and substance use disorders has not been documented in non-clinical students in Sub-Saharan Africa, and Kenya in particular.
AIMS: To document the risk level of ASD and its traits in a Kenyan student population (high school, college and university) using the Autism-Spectrum Quotient (AQ); and to determine the associations between ASD and other psychiatric and substance use disorders.
METHOD: This was a cross-sectional study among students (
RESULTS: Of the total sample, 54 (0.56%) were at high risk of ASD. Sociodemographic differences …
Transcranial Focused Ultrasound-Induced Blood‒Brain Barrier Opening In Mice Without Shaving Hairs, Lu Xu, Yan Gong, Chih-Yen Chien, Eric Leuthardt, Hong Chen
Transcranial Focused Ultrasound-Induced Blood‒Brain Barrier Opening In Mice Without Shaving Hairs, Lu Xu, Yan Gong, Chih-Yen Chien, Eric Leuthardt, Hong Chen
2020-Current year OA Pubs
Acoustic coupling through hairs remains a challenge to performing transcranial-focused ultrasound procedures. Here, we demonstrated that this challenge could be addressed by using oil as the coupling medium, leveraging oil's high affinity to hairs due to their inherent hydrophobicity. We compared focused ultrasound-induced blood-brain barrier opening (FUS-BBBO) outcomes in mice under three coupling conditions: oil with hairs ("oil + hairs"), ultrasound gel with hair shaving ("ultrasound gel + no hair"), and ultrasound gel with hairs ("ultrasound gel + hairs"). The quality of the coupling was evaluated by [Formula: see text]-weighted magnetic resonance imaging (MRI) and passive cavitation detection (PCD). The …
Differential Processing Of Risk And Reward In Delinquent And Non-Delinquent Youth, Natasha Duell, Michael T Perino, Ethan M Mccormick, Eva H Telzer
Differential Processing Of Risk And Reward In Delinquent And Non-Delinquent Youth, Natasha Duell, Michael T Perino, Ethan M Mccormick, Eva H Telzer
2020-Current year OA Pubs
The present study examined the behavioral and neural differences in risky decision-making between delinquent (n = 23) and non-delinquent (n = 27) youth ages 13-17 years (M = 16, SD = 0.97) in relation to reward processing. While undergoing functional neuroimaging, participants completed an experimental risk task wherein they received feedback about the riskiness of their behavior in the form of facial expressions that morphed from happy to angry. Behavioral results indicated that delinquent youth took fewer risks and earned fewer rewards on the task than non-delinquent youth. Results from whole-brain analyses indicated no group differences in sensitivity to punishments …
Phase Iii Pivotal Comparative Clinical Trial Of Intranasal (Incovacc) And Intramuscular Covid 19 Vaccine (Covaxin®), Chandramani Singh, Michael S Diamond, David T Curiel, Et Al.
Phase Iii Pivotal Comparative Clinical Trial Of Intranasal (Incovacc) And Intramuscular Covid 19 Vaccine (Covaxin®), Chandramani Singh, Michael S Diamond, David T Curiel, Et Al.
2020-Current year OA Pubs
One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin
Vegf-B Prevents Excessive Angiogenesis By Inhibiting Fgf2/Fgfr1 Pathway, Chunsik Lee, David M Ornitz, Et Al.
Vegf-B Prevents Excessive Angiogenesis By Inhibiting Fgf2/Fgfr1 Pathway, Chunsik Lee, David M Ornitz, Et Al.
2020-Current year OA Pubs
Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting …
Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J. Hultgren, Jennifer N. Walker, Ritwij Kulkarni
Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J. Hultgren, Jennifer N. Walker, Ritwij Kulkarni
2020-Current year OA Pubs
Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in
Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial, Chris A Rees, Fahd Ahmad, Et Al.
Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial, Chris A Rees, Fahd Ahmad, Et Al.
2020-Current year OA Pubs
BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.
METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …
A Survey Of Surgical Patients' Perspectives And Preferences Towards General Anesthesia Techniques And Shared-Decision Making, Bethany R Tellor Pennington, Mary C Politi, Arbi Ben Abdallah, Allison M Janda, Ingrid Eshun-Wilsonova, Nastassjia G Debourbon, Lilly Siderowf, Heidi Klosterman, Sachin Kheterpal, Michael S Avidan
A Survey Of Surgical Patients' Perspectives And Preferences Towards General Anesthesia Techniques And Shared-Decision Making, Bethany R Tellor Pennington, Mary C Politi, Arbi Ben Abdallah, Allison M Janda, Ingrid Eshun-Wilsonova, Nastassjia G Debourbon, Lilly Siderowf, Heidi Klosterman, Sachin Kheterpal, Michael S Avidan
2020-Current year OA Pubs
BACKGROUND: The decision about which type of general anesthetic to administer is typically made by the clinical team without patient engagement. This study examined patients' preferences, experiences, attitudes, beliefs, perceptions, and perceived social norms about anesthesia and about engaging in the decision regarding general anesthetic choice with their clinician.
METHODS: We conducted a survey in the United States, sent to a panel of surgical patients through Qualtrics (Qualtrics, Provo, UT) from March 2022 through May 2022. Questions were developed based on the Theory of Planned Behavior and validated measures were used when available. A patient partner who had experienced both …
Brain-Derived Neurotrophic Factor Dysregulation As An Essential Pathological Feature In Huntington's Disease: Mechanisms And Potential Therapeutics, Andrew Speidell, Noman Bin Abid, Hiroko Yano
Brain-Derived Neurotrophic Factor Dysregulation As An Essential Pathological Feature In Huntington's Disease: Mechanisms And Potential Therapeutics, Andrew Speidell, Noman Bin Abid, Hiroko Yano
2020-Current year OA Pubs
Brain-derived neurotrophic factor (BDNF) is a major neurotrophin whose loss or interruption is well established to have numerous intersections with the pathogenesis of progressive neurological disorders. There is perhaps no greater example of disease pathogenesis resulting from the dysregulation of BDNF signaling than Huntington's disease (HD)-an inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive impairments associated with basal ganglia dysfunction and the ultimate death of striatal projection neurons. Investigation of the collection of mechanisms leading to BDNF loss in HD highlights this neurotrophin's importance to neuronal viability and calls attention to opportunities for therapeutic interventions. Using electronic database searches …
Kinase Inhibitor Pulldown Assay Identifies A Chemotherapy Response Signature In Triple-Negative Breast Cancer Based On Purine-Binding Proteins, Junkai Wang, Alexander B Saltzman, Eric J Jaehnig, Jonathan T Lei, Anna Malovannaya, Matthew V Holt, Meggie N Young, Mothaffar F Rimawi, Foluso O Ademuyiwa, Meenakshi Anurag, Beom-Jun Kim, Matthew J Ellis
Kinase Inhibitor Pulldown Assay Identifies A Chemotherapy Response Signature In Triple-Negative Breast Cancer Based On Purine-Binding Proteins, Junkai Wang, Alexander B Saltzman, Eric J Jaehnig, Jonathan T Lei, Anna Malovannaya, Matthew V Holt, Meggie N Young, Mothaffar F Rimawi, Foluso O Ademuyiwa, Meenakshi Anurag, Beom-Jun Kim, Matthew J Ellis
2020-Current year OA Pubs
UNLABELLED: Triple-negative breast cancer (TNBC) constitutes 10%-15% of all breast tumors. The current standard of care is multiagent chemotherapy, which is effective in only a subset of patients. The original objective of this study was to deploy a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) to identify kinases elevated in non-pCR (pathologic complete response) cases for therapeutic targeting. Frozen optimal cutting temperature compound-embedded core needle biopsies were obtained from 43 patients with TNBC before docetaxel- and carboplatin-based neoadjuvant chemotherapy. KIPA was applied to the native tumor lysates that were extracted from samples with high tumor content. Seven percent of …
Mechanical Stiffness And Anisotropy Measured By Mre During Brain Development In The Minipig, Shuaihu Wang, Charlotte A Guertler, Ruth J Okamoto, Curtis L Johnson, Matthew D J Mcgarry, Philip V Bayly
Mechanical Stiffness And Anisotropy Measured By Mre During Brain Development In The Minipig, Shuaihu Wang, Charlotte A Guertler, Ruth J Okamoto, Curtis L Johnson, Matthew D J Mcgarry, Philip V Bayly
2020-Current year OA Pubs
The relationship between brain development and mechanical properties of brain tissue is important, but remains incompletely understood, in part due to the challenges in measuring these properties longitudinally over time. In addition, white matter, which is composed of aligned, myelinated, axonal fibers, may be mechanically anisotropic. Here we use data from magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) to estimate anisotropic mechanical properties in six female Yucatan minipigs at ages from 3 to 6 months. Fiber direction was estimated from the principal axis of the diffusion tensor in each voxel. Harmonic shear waves in the brain were excited …
Discovery And Targeting Of A Noncanonical Mechanism Of Sarcoma Resistance To Adi-Peg20 Mediated By The Microenvironment, Leonard C Rogers, Jeff C Kremer, Caitlyn B Brashears, Zongtao Lin, Alliny C S Bastos, Adriana Baker, Nicole Fettig, Dong Zhou, Kooresh I Shoghi, Carina A Dehner, John S A Chrisinger, Benjamin A Garcia, Toshinao Oyama, Brian A Van Tine, Et Al.
Discovery And Targeting Of A Noncanonical Mechanism Of Sarcoma Resistance To Adi-Peg20 Mediated By The Microenvironment, Leonard C Rogers, Jeff C Kremer, Caitlyn B Brashears, Zongtao Lin, Alliny C S Bastos, Adriana Baker, Nicole Fettig, Dong Zhou, Kooresh I Shoghi, Carina A Dehner, John S A Chrisinger, Benjamin A Garcia, Toshinao Oyama, Brian A Van Tine, Et Al.
2020-Current year OA Pubs
PURPOSE: Many cancers lack argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of arginine biosynthesis. This deficiency causes arginine auxotrophy, targetable by extracellular arginine-degrading enzymes such as ADI-PEG20. Long-term tumor resistance has thus far been attributed solely to ASS1 reexpression. This study examines the role of ASS1 silencing on tumor growth and initiation and identifies a noncanonical mechanism of resistance, aiming to improve clinical responses to ADI-PEG20.
EXPERIMENTAL DESIGN: Tumor initiation and growth rates were measured for a spontaneous Ass1 knockout (KO) murine sarcoma model. Tumor cell lines were generated, and resistance to arginine deprivation therapy was studied in vitro and …
Impact Of A Double Catastrophe, War And Covid-19, On Health Service Utilization Of A Tertiary Care Hospital In Tigray: An Interrupted Time-Series Study, Hiluf Ebuy Abraha, L Lewis Wall, Et Al.
Impact Of A Double Catastrophe, War And Covid-19, On Health Service Utilization Of A Tertiary Care Hospital In Tigray: An Interrupted Time-Series Study, Hiluf Ebuy Abraha, L Lewis Wall, Et Al.
2020-Current year OA Pubs
BACKGROUND: In developing nations with fragile healthcare systems, the effect of war is likely to be much worse than it would be in more developed countries. The presence of COVID-19 will also likely exacerbate the war's impact. This study set out to determine the effect of armed conflict and the COVID-19 pandemic on health service utilization at Ayder Comprehensive Specialized Hospital, in the Tigray region of Ethiopia.
METHODS: An interrupted time-series study design was used to analyze patient visits over forty-eight consecutive months (from July 2017 to June 2021) at inpatient, outpatient, and emergency departments. Data were analyzed using segmented …
Using Audit And Feedback To Guide Tailored Implementations Of Measurement-Based Care In Community Mental Health: A Multiple Case Study, Mira D H Snider, Meredith R Boyd, Madison R Walker, Byron J Powell, Cara C Lewis
Using Audit And Feedback To Guide Tailored Implementations Of Measurement-Based Care In Community Mental Health: A Multiple Case Study, Mira D H Snider, Meredith R Boyd, Madison R Walker, Byron J Powell, Cara C Lewis
2020-Current year OA Pubs
BACKGROUND: Audit and feedback (A&F) is an implementation strategy that can facilitate implementation tailoring by identifying gaps between desired and actual clinical care. While there are several theory-based propositions on which A&F components lead to better implementation outcomes, many have not been empirically investigated, and there is limited guidance for stakeholders when applying A&F in practice. The current study aims to illustrate A&F procedures in six community mental health clinics, with an emphasis on reporting A&F components that are relevant to theories of how feedback elicits behavior change.
METHODS: Six clinics from a larger trial using a tailored approach to …
Analysis Of Superficial Subcutaneous Fat Camper's And Scarpa's Fascia In A United States Cohort, David Z Chen, Aravinda Ganapathy, Yash Nayak, Christopher Mejias, Grace L Bishop, Vincent M Mellnick, David H Ballard
Analysis Of Superficial Subcutaneous Fat Camper's And Scarpa's Fascia In A United States Cohort, David Z Chen, Aravinda Ganapathy, Yash Nayak, Christopher Mejias, Grace L Bishop, Vincent M Mellnick, David H Ballard
2020-Current year OA Pubs
Together, the Camper's and Scarpa's fasciae form the superficial fat layer of the abdominal wall. Though they have clinical and surgical relevance, little is known about their role in body composition across diverse patient populations. This study aimed to determine the relationship between patient characteristics, including sex and body mass index, and the distribution of Camper's and Scarpa's fascial layers in the abdominal wall. A total of 458 patients' abdominal CT examinations were segmented via CoreSlicer 1.0 to determine the surface area of each patient's Camper's, Scarpa's, and visceral fascia layers. The reproducibility of segmentation was corroborated by an inter-rater …
Pediatric Experience And Outcomes From The First Single-Vault Compact Proton Therapy Center, Stephanie M Perkins, Sabrina Prime, Michael Watts, Jiayi Huang, Tianyu Zhao
Pediatric Experience And Outcomes From The First Single-Vault Compact Proton Therapy Center, Stephanie M Perkins, Sabrina Prime, Michael Watts, Jiayi Huang, Tianyu Zhao
2020-Current year OA Pubs
The first single-vault compact proton therapy center opened in 2013, utilizing a gantry-mounted synchrocylotron. The center was placed within a large academic radiation oncology department with a high priority for pediatric cancer care. Here we performed a retrospective study of pediatric (≤21 years) patients treated with proton therapy at our institution between 2013-2022. Patient, tumor, and treatment characteristics were obtained including race, socioeconomic status, insurance type, distance travelled, need for anesthesia, and outside referrals for proton therapy. In total, 250 pediatric patients were treated with proton therapy comprising 18% of our proton patient volume. Median follow-up was 3.1 years, 38.4% …
The Effects Of Advanced Factor Analysis Approaches On Outcomes In Randomised Trials For Depression: Protocol For Secondary Analysis Of Individual Participant Data, Frank Doyle, David Byrne, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Shane Kelly, Stephen Mcbride, Emma Wallace, Fiona Boland
The Effects Of Advanced Factor Analysis Approaches On Outcomes In Randomised Trials For Depression: Protocol For Secondary Analysis Of Individual Participant Data, Frank Doyle, David Byrne, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Shane Kelly, Stephen Mcbride, Emma Wallace, Fiona Boland
2020-Current year OA Pubs
BACKGROUND: Modern psychometric methods make it possible to eliminate nonperforming items and reduce measurement error. Application of these methods to existing outcome measures can reduce variability in scores, and may increase treatment effect sizes in depression treatment trials.
AIMS: We aim to determine whether using confirmatory factor analysis techniques can provide better estimates of the true effects of treatments, by conducting secondary analyses of individual patient data from randomised trials of antidepressant therapies.
METHOD: We will access individual patient data from antidepressant treatment trials through Clinicalstudydatarequest.com and Vivli.org, specifically targeting studies that used the Hamilton Rating Scale for Depression (HRSD) …
Understanding Disruptions In Cancer Care To Reduce Increased Cancer Burden, Kia L Davis, Nicole Ackermann, Lisa M Klesges, Nora Leahy, Callie Walsh-Bailey, Sarah Humble, Bettina Drake, Vetta L Sanders Thompson
Understanding Disruptions In Cancer Care To Reduce Increased Cancer Burden, Kia L Davis, Nicole Ackermann, Lisa M Klesges, Nora Leahy, Callie Walsh-Bailey, Sarah Humble, Bettina Drake, Vetta L Sanders Thompson
2020-Current year OA Pubs
BACKGROUND: This study seeks to understand how and for whom COVID-19 disrupted cancer care to understand the potential for cancer health disparities across the cancer prevention and control continuum.
METHODS: In this cross-sectional study, participants age 30+residing in an 82-county region in Missouri and Illinois completed an online survey from June-August 2020. Descriptive statistics were calculated for all variables separately and by care disruption status. Logistic regression modeling was conducted to determine the correlates of care disruption.
RESULTS: Participants (N=680) reported 21% to 57% of cancer screening or treatment appointments were canceled/postponed from March 2020 through the end of 2020. …
Rho Enhancers Play Unexpectedly Minor Roles In Rhodopsin Transcription And Rod Cell Integrity, Chi Sun, Philip A Ruzycki, Shiming Chen
Rho Enhancers Play Unexpectedly Minor Roles In Rhodopsin Transcription And Rod Cell Integrity, Chi Sun, Philip A Ruzycki, Shiming Chen
2020-Current year OA Pubs
Enhancers function with a basal promoter to control the transcription of target genes. Enhancer regulatory activity is often studied using reporter-based transgene assays. However, unmatched results have been reported when selected enhancers are silenced in situ. In this study, using genomic deletion analysis in mice, we investigated the roles of two previously identified enhancers and the promoter of the Rho gene that codes for the visual pigment rhodopsin. The Rho gene is robustly expressed by rod photoreceptors of the retina, and essential for the subcellular structure and visual function of rod photoreceptors. Mutations in RHO cause severe vision loss in …