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Full-Text Articles in Entire DC Network
Integrative Analysis Of Pathogenic Variants In Glucose-6-Phosphatase Based On An Alphafold2 Model, Matt Sinclair, Richard A Stein, Jonathan H Sheehan, Emily M Hawes, Richard M O'Brien, Emad Tajkhorshid, Derek P Claxton
Integrative Analysis Of Pathogenic Variants In Glucose-6-Phosphatase Based On An Alphafold2 Model, Matt Sinclair, Richard A Stein, Jonathan H Sheehan, Emily M Hawes, Richard M O'Brien, Emad Tajkhorshid, Derek P Claxton
2020-Current year OA Pubs
Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. In this study, we determine the atomic interactions …
Bullous Pemphigoid With Prominent Mucosal Involvement In The Setting Of Renal Allograft Rejection, Wesley T Hodges, Ahmed H Badawi, Ilana S Rosman, Amy C Musiek, Leonid Shmuylovich
Bullous Pemphigoid With Prominent Mucosal Involvement In The Setting Of Renal Allograft Rejection, Wesley T Hodges, Ahmed H Badawi, Ilana S Rosman, Amy C Musiek, Leonid Shmuylovich
2020-Current year OA Pubs
No abstract provided.
Angptl3 Deficiency Impairs Lipoprotein Production And Produces Adaptive Changes In Hepatic Lipid Metabolism, Kendall H Burks, Yan Xie, In-Hyuk Jung, Sandip Mukherjee, Paul Lee, Upasana Pudupakkam, Ryan Wagoner, Ved Patel, Katherine Santana, Arturo Alisio, Brian N Finck, Nicholas O Davidson, Nathan O Stitziel, Et Al.
Angptl3 Deficiency Impairs Lipoprotein Production And Produces Adaptive Changes In Hepatic Lipid Metabolism, Kendall H Burks, Yan Xie, In-Hyuk Jung, Sandip Mukherjee, Paul Lee, Upasana Pudupakkam, Ryan Wagoner, Ved Patel, Katherine Santana, Arturo Alisio, Brian N Finck, Nicholas O Davidson, Nathan O Stitziel, Et Al.
2020-Current year OA Pubs
Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted protein and therapeutic target for reducing plasma triglyceride-rich lipoproteins and low-density lipoprotein (LDL) cholesterol. Although ANGPTL3 modulates the metabolism of circulating lipoproteins, its role in triglyceride-rich lipoprotein assembly and secretion remains unknown. CRISPR-associated protein 9 (CRISPR/Cas9) was used to target ANGPTL3 in HepG2 cells (ANGPTL3
Show Me Ckdintercept Initiative: A Collective Impact Approach To Improve Population Health In Missouri, Katelyn Laue, Megan Schultz, Elizabeth Talbot-Montgomery, Alexandra Garrick, Anuja Java, Christine Corbett, Dana M Lammert, Joanna Rogers, Kathleen Davis, Kunal Malhotra, Marie Philipneri, Mary Ann Kimbel, Reem A Mustafa, Valerie Hardesty
Show Me Ckdintercept Initiative: A Collective Impact Approach To Improve Population Health In Missouri, Katelyn Laue, Megan Schultz, Elizabeth Talbot-Montgomery, Alexandra Garrick, Anuja Java, Christine Corbett, Dana M Lammert, Joanna Rogers, Kathleen Davis, Kunal Malhotra, Marie Philipneri, Mary Ann Kimbel, Reem A Mustafa, Valerie Hardesty
2020-Current year OA Pubs
Ninety percent of people with chronic kidney disease (CKD) remain undiagnosed, most people at risk do not receive guideline-concordant testing, and disparities of care and outcomes exist across all stages of the disease. To improve CKD diagnosis and management across primary care, the National Kidney Foundation launched a collective impact (CI) initiative known as Show Me CKDintercept. The initiative was implemented in Missouri, USA from January 2021 to June 2022, using a data strategy, stakeholder engagement and relationship mapping, learning in action working groups (LAWG), and a virtual leadership summit. The Reach, Effectiveness, Adoption, Implementation, and Maintenance framework was used …
Surgically Implanted Endovascular, Microaxial Left Ventricular Assist Device: A Single Institution Study, Erin M Schumer, Yun Zhu Bai, Kunal D Kotkar, M Faraz Masood, Akinobu Itoh, Joel D Schilling, Gregory A Ewald, Marci S Damiano, Irene Fischer, Tsuyoshi Kaneko, Ralph J Damiano, Amit Pawale
Surgically Implanted Endovascular, Microaxial Left Ventricular Assist Device: A Single Institution Study, Erin M Schumer, Yun Zhu Bai, Kunal D Kotkar, M Faraz Masood, Akinobu Itoh, Joel D Schilling, Gregory A Ewald, Marci S Damiano, Irene Fischer, Tsuyoshi Kaneko, Ralph J Damiano, Amit Pawale
2020-Current year OA Pubs
OBJECTIVE: The Impella 5.5 (Abiomed, Inc), a surgically implanted endovascular microaxial left ventricular assist device, is increasingly used worldwide and there have been more than 10,000 implants. The purpose of this study is to describe a large-volume, single-center experience with the use of the Impella 5.5.
METHODS: Data were obtained retrospectively from patients supported with the Impella 5.5 implanted at our institution from May 1, 2020, to December 31, 2022. Demographic, operative, and postoperative outcomes for each group are described. Results are reported in median (interquartile range) or n (%). The entire cohort was divided into 5 main groups based …
Top 50 Most-Cited Studies About Osteochondritis Dissecans, Nicholas D Thomas, Raegan Mahler, Kylie Krombholz, Brendan Williams, Ted Ganley, Jeffrey J Nepple, Kevin Shea
Top 50 Most-Cited Studies About Osteochondritis Dissecans, Nicholas D Thomas, Raegan Mahler, Kylie Krombholz, Brendan Williams, Ted Ganley, Jeffrey J Nepple, Kevin Shea
2020-Current year OA Pubs
PURPOSE: To determine the 50 most frequently cited studies on osteochondritis dissecans (OCD) and to conduct a bibliometric analysis of these studies.
METHODS: We performed a search within the Clarivate Web of Science database, identifying articles published before December 2022 that encompass topics related to OCD. The search was conducted using the keywords "Osteochondritis Dissecans OR Osteochondritis OR Dissecans."Search results were then filtered using predetermined guidelines and criteria, and the 50 most-cited articles were selected for analysis. Extracted data included title, journal, design, main topic, joint, citations, year, country of origin, and level of evidence.
RESULTS: The search yielded 3,865 …
Screening For Problematic Opioid Use In The Emergency Department: Comparison Of Two Screening Measures, Brittany E Punches, Caroline E Freiermuth, Jon E Sprague, Jennifer L Brown, Elizabeth Hutzel-Dunham, Joshua Lambert, Robert Braun, Andrew Littlefield, Jennifer A Frey, Daniel J Bachmann, Jason J Bischof, Michael V Pantalon, Rachel M Ancona, David F Kisor, Michael S Lyons
Screening For Problematic Opioid Use In The Emergency Department: Comparison Of Two Screening Measures, Brittany E Punches, Caroline E Freiermuth, Jon E Sprague, Jennifer L Brown, Elizabeth Hutzel-Dunham, Joshua Lambert, Robert Braun, Andrew Littlefield, Jennifer A Frey, Daniel J Bachmann, Jason J Bischof, Michael V Pantalon, Rachel M Ancona, David F Kisor, Michael S Lyons
2020-Current year OA Pubs
STUDY OBJECTIVE: Earlier intervention for opioid use disorder (OUD) may reduce long-term health implications. Emergency departments (EDs) in the United States treat millions with OUD annually who may not seek care elsewhere. Our objectives were (1) to compare two screening measures for OUD characterization in the ED and (2) to determine the proportion of ED patients screening positive for OUD and those who endorse other substance use to guide future screening programs.
METHODS: A cross-sectional study of randomly selected adult patients presenting to three Midwestern US EDs were enrolled, with duplicate patients excluded. Surveys were administered via research assistant and …
Optimal Approaches To Analyzing Functional Mri Data In Glioma Patients, Ki Yun Park, Joshua S Shimony, Satrajit Chakrabarty, Aaron B Tanenbaum, Carl D Hacker, Kara M Donovan, Patrick H Luckett, Mikhail Milchenko, Aristeidis Sotiras, Daniel S Marcus, Eric C Leuthardt, Abraham Z Snyder
Optimal Approaches To Analyzing Functional Mri Data In Glioma Patients, Ki Yun Park, Joshua S Shimony, Satrajit Chakrabarty, Aaron B Tanenbaum, Carl D Hacker, Kara M Donovan, Patrick H Luckett, Mikhail Milchenko, Aristeidis Sotiras, Daniel S Marcus, Eric C Leuthardt, Abraham Z Snyder
2020-Current year OA Pubs
BACKGROUND: Resting-state fMRI is increasingly used to study the effects of gliomas on the functional organization of the brain. A variety of preprocessing techniques and functional connectivity analyses are represented in the literature. However, there so far has been no systematic comparison of how alternative methods impact observed results.
NEW METHOD: We first surveyed current literature and identified alternative analytical approaches commonly used in the field. Following, we systematically compared alternative approaches to atlas registration, parcellation scheme, and choice of graph-theoretical measure as regards differentiating glioma patients (N = 59) from age-matched reference subjects (N = 163).
RESULTS: Our results …
Creation Of A National Emergency Medicine Medical Education Journal Club, Jessica Pelletier, James Ahn, Andrew Golden, Caroline Astemborski, Michelle D. Lall, Albert Kim, Sara Dimeo
Creation Of A National Emergency Medicine Medical Education Journal Club, Jessica Pelletier, James Ahn, Andrew Golden, Caroline Astemborski, Michelle D. Lall, Albert Kim, Sara Dimeo
2020-Current year OA Pubs
Background There are a relatively limited number of emergency medicine (EM) medical education (MedEd) fellowships with few trainees at each program, creating barriers to local collaboration and networking. While best practices for developing MedEd journal clubs exist, there has not been an established national EM MedEd journal club. To address this need, we created a national journal club, the Council of Residency Directors (CORD) MedEd Journal Club (MEJC), to facilitate collaboration and networking opportunities by providing a synchronous online journal club. Objectives Our primary objective was to create a network for collaboration across geographical barriers to form a virtual community …
Serological Assays For Differentiating Natural Covid-19 Infection From Vaccine Induced Immunity, Samuel M S Cheng, Gaya K Amarasinghe, Et Al.
Serological Assays For Differentiating Natural Covid-19 Infection From Vaccine Induced Immunity, Samuel M S Cheng, Gaya K Amarasinghe, Et Al.
2020-Current year OA Pubs
BACKGROUND: Natural SARS-CoV-2 infection may elicit antibodies to a range of viral proteins including non-structural protein ORF8. RNA, adenovirus vectored and sub-unit vaccines expressing SARS-CoV-2 spike would be only expected to elicit S-antibodies and antibodies to distinct domains of nucleocapsid (N) protein may reliably differentiate infection from vaccine-elicited antibody. However, inactivated whole virus vaccines may potentially elicit antibody to wider range of viral proteins, including N protein. We hypothesized that antibody to ORF8 protein will discriminate natural infection from vaccination irrespective of vaccine type.
METHODS: We optimized and validated the anti-ORF8 and anti-N C-terminal domain (NCTD) ELISA assays using sera …
Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael D Chuong, Hyun Kim, Lauren E Henke, Alex T Price, Et Al.
Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael D Chuong, Hyun Kim, Lauren E Henke, Alex T Price, Et Al.
2020-Current year OA Pubs
BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.
MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …
Associations Between Early Trajectories Of Amygdala Development And Later School-Age Anxiety In Two Longitudinal Samples, Catherine A Burrows, Kelly N Botteron, John R Pruett Jr, Et Al.
Associations Between Early Trajectories Of Amygdala Development And Later School-Age Anxiety In Two Longitudinal Samples, Catherine A Burrows, Kelly N Botteron, John R Pruett Jr, Et Al.
2020-Current year OA Pubs
Amygdala function is implicated in the pathogenesis of autism spectrum disorder (ASD) and anxiety. We investigated associations between early trajectories of amygdala growth and anxiety and ASD outcomes at school age in two longitudinal studies: high- and low-familial likelihood for ASD, Infant Brain Imaging Study (IBIS, n = 257) and typically developing (TD) community sample, Early Brain Development Study (EBDS, n = 158). Infants underwent MRI scanning at up to 3 timepoints from neonate to 24 months. Anxiety was assessed at 6-12 years. Linear multilevel modeling tested whether amygdala volume growth was associated with anxiety symptoms at school age. In …
Bintrafusp Alfa With Ccrt Followed By Bintrafusp Alfa Versus Placebo With Ccrt Followed By Durvalumab In Patients With Unresectable Stage Iii Nsclc: A Phase 2 Randomized Study, Everett E Vokes, Clifford G Robinson, Et Al.
Bintrafusp Alfa With Ccrt Followed By Bintrafusp Alfa Versus Placebo With Ccrt Followed By Durvalumab In Patients With Unresectable Stage Iii Nsclc: A Phase 2 Randomized Study, Everett E Vokes, Clifford G Robinson, Et Al.
2020-Current year OA Pubs
INTRODUCTION: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment.
METHODS: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 …
Semaglutide Improves Metabolic Dysfunction-Associated Steatohepatitis: A 10-Year Retrospective Study, Parth Shah, Megan White, Alex Sievert, Alexander Conway, Adam Kneepkens, Gregory Sayuk, Mauricio Lisker-Melman, Jill Elwing
Semaglutide Improves Metabolic Dysfunction-Associated Steatohepatitis: A 10-Year Retrospective Study, Parth Shah, Megan White, Alex Sievert, Alexander Conway, Adam Kneepkens, Gregory Sayuk, Mauricio Lisker-Melman, Jill Elwing
2020-Current year OA Pubs
BACKGROUND AND AIMS: Semaglutide has been studied in patients with metabolic dysfunction-associated steatohepatitis (MASH) due to potential benefit from weight loss on liver inflammation. However, preclinical studies suggest that MASH improvement may be independent of weight loss. We aim to assess the impact of semaglutide on MASH in relation to weight loss.
METHODS: This retrospective study included 420 patients with diabetes on semaglutide for at least 12 months between 2011 and 2022. Exclusion criteria were liver disease other than MASH, decompensated cirrhosis, malignancy, and bariatric surgery. Primary endpoints were clinically significant improvements in AST or ALT (mean difference > 6.3 U/L …
Assessment Of Bovine Cortical Bone Fracture Behavior Using Impact Microindentation As A Surrogate Of Fracture Toughness, Babak Jahani, Rachana Vaidya, James M Jin, Donald A Aboytes, Kaitlyn S Broz, Siva Krothapalli, Bhanuteja Pujari, Walee M Baig, Simon Y Tang
Assessment Of Bovine Cortical Bone Fracture Behavior Using Impact Microindentation As A Surrogate Of Fracture Toughness, Babak Jahani, Rachana Vaidya, James M Jin, Donald A Aboytes, Kaitlyn S Broz, Siva Krothapalli, Bhanuteja Pujari, Walee M Baig, Simon Y Tang
2020-Current year OA Pubs
The fracture behavior of bone is critically important for evaluating its mechanical competence and ability to resist fractures. Fracture toughness is an intrinsic material property that quantifies a material's ability to withstand crack propagation under controlled conditions. However, properly conducting fracture toughness testing requires the access to calibrated mechanical load frames and the destructive testing of bone samples, and therefore fracture toughness tests are clinically impractical. Impact microindentation mimicks certain aspects of fracture toughness measurements, but its relationship with fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh …
Longitudinal Predictors Of Health-Related Quality Of Life In Isolated Dystonia, Johanna Junker, Joel S Perlmutter, Et Al.
Longitudinal Predictors Of Health-Related Quality Of Life In Isolated Dystonia, Johanna Junker, Joel S Perlmutter, Et Al.
2020-Current year OA Pubs
OBJECTIVE: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia.
METHODS: Out of 603 dystonia patients prospectively enrolled in the Natural History Dystonia Coalition study, 155 were assessed three times within 2 years for HR-QoL, symptoms of depression, generalized anxiety disorder (GAD), and social anxiety disorder (SAD), as well as dystonia severity and dystonic tremor. In addition, the impact of botulinum neurotoxin (BoNT) injections on HR-QoL was evaluated after 1 year.
RESULTS: Depressive symptoms at baseline predicted lower HR-QoL on all subscales after 2 years (all p ≤ 0.001). …
Mucosal Boosting Enhances Vaccine Protection Against Sars-Cov-2 In Macaques, Katherine Mcmahan, Adrianus C M Boon, Et Al.
Mucosal Boosting Enhances Vaccine Protection Against Sars-Cov-2 In Macaques, Katherine Mcmahan, Adrianus C M Boon, Et Al.
2020-Current year OA Pubs
A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants
Current Understanding Of The Alzheimer's Disease-Associated Microbiome And Therapeutic Strategies, Dong-Oh Seo, David M Holtzman
Current Understanding Of The Alzheimer's Disease-Associated Microbiome And Therapeutic Strategies, Dong-Oh Seo, David M Holtzman
2020-Current year OA Pubs
Alzheimer's disease (AD) is a fatal progressive neurodegenerative disease. Despite tremendous research efforts to understand this complex disease, the exact pathophysiology of the disease is not completely clear. Recently, anti-Aβ antibodies have been shown to remove amyloid from the brain and slow the clinical progression of mild dementia by ~30%. However, exploring alternative strategies is crucial to understanding and developing more effective therapeutic interventions. In recent years, the microbiota-gut-brain axis has received significant attention in the AD field. Numerous studies have suggested that alterations in the gut microbiota composition are associated with the progression of AD, and several underlying mechanisms …
The Impact Of Patterns In Linkage Disequilibrium And Sequencing Quality On The Imprint Of Balancing Selection, Tristan J Hayeck, Yang Li, Timothy L Mosbruger, Jonathan P Bradfield, Adam G Gleason, George Damianos, Grace Tzun-Wen Shaw, Jamie L Duke, Laura K Conlin, Tychele N Turner, Marcelo A Fernández-Viña, Mahdi Sarmady, Dimitri S Monos
The Impact Of Patterns In Linkage Disequilibrium And Sequencing Quality On The Imprint Of Balancing Selection, Tristan J Hayeck, Yang Li, Timothy L Mosbruger, Jonathan P Bradfield, Adam G Gleason, George Damianos, Grace Tzun-Wen Shaw, Jamie L Duke, Laura K Conlin, Tychele N Turner, Marcelo A Fernández-Viña, Mahdi Sarmady, Dimitri S Monos
2020-Current year OA Pubs
Regions under balancing selection are characterized by dense polymorphisms and multiple persistent haplotypes, along with other sequence complexities. Successful identification of these patterns depends on both the statistical approach and the quality of sequencing. To address this challenge, at first, a new statistical method called LD-ABF was developed, employing efficient Bayesian techniques to effectively test for balancing selection. LD-ABF demonstrated the most robust detection of selection in a variety of simulation scenarios, compared against a range of existing tests/tools (Tajima's D, HKA, Dng, BetaScan, and BalLerMix). Furthermore, the impact of the quality of sequencing on detection of balancing selection was …
Feasibility Of Interleukin-6 Receptor Blockade In Cardiac Antibody-Mediated Rejection, April A Pottebaum, Spenser E. January, Chang Liu, Steven Lavine, Joel D. Schilling, Kory J. Lavine
Feasibility Of Interleukin-6 Receptor Blockade In Cardiac Antibody-Mediated Rejection, April A Pottebaum, Spenser E. January, Chang Liu, Steven Lavine, Joel D. Schilling, Kory J. Lavine
2020-Current year OA Pubs
BACKGROUND: Antibody-mediated rejection (AMR) remains a significant cause of heart transplant mortality with few effective therapies.
METHODS: This study aimed to describe initial experience of using interleukin-6 receptor blockade with tocilizumab in the treatment of acute cardiac AMR at Barnes-Jewish Hospital/Washington University Transplant Center from July 2017 to May 2021 (n = 7). Clinical, echocardiographic, and serum alloantibody data were analyzed before and after treatment.
RESULTS: All participants demonstrated marked improvement in functional status. Echocardiographic data following 4-6 mo of tocilizumab revealed significant improvements in biventricular systolic function for all participants. Consistent reductions in donor-specific HLA or angiotensin type I …
Covid-19 Vaccine Perspective From Adolescents' Lens In The Us, Meher Garg, Arnav A. Nagrecha, Ruchi Gupta, Makeba Williams
Covid-19 Vaccine Perspective From Adolescents' Lens In The Us, Meher Garg, Arnav A. Nagrecha, Ruchi Gupta, Makeba Williams
2020-Current year OA Pubs
Introduction The COVID-19 pandemic has presented an unprecedented global health issue. The World Health Organization estimates 773 million confirmed cases and 7 million deaths. Vaccination continues to be the most effective way to prevent COVID-19 and has demonstrated safety and efficacy in all age groups. Though a lot of studies have looked at COVID-19 vaccination acceptance and hesitancy in adults, there is scarce research addressing adolescent vaccination readiness. COVID-19 infection in this age group may result in lost school days, school and community transmission, and loss of productivity for parents. Aim This study aims to determine COVID-19 vaccination rates and …
Structural Biases In Disordered Proteins Are Prevalent In The Cell, David Moses, Karina Guadalupe, Feng Yu, Eduardo Flores, Anthony R Perez, Ralph Mcanelly, Nora M Shamoon, Gagandeep Kaur, Estefania Cuevas-Zepeda, Andrea D Merg, Erik W Martin, Alex S Holehouse, Shahar Sukenik
Structural Biases In Disordered Proteins Are Prevalent In The Cell, David Moses, Karina Guadalupe, Feng Yu, Eduardo Flores, Anthony R Perez, Ralph Mcanelly, Nora M Shamoon, Gagandeep Kaur, Estefania Cuevas-Zepeda, Andrea D Merg, Erik W Martin, Alex S Holehouse, Shahar Sukenik
2020-Current year OA Pubs
Intrinsically disordered proteins and protein regions (IDPs) are prevalent in all proteomes and are essential to cellular function. Unlike folded proteins, IDPs exist in an ensemble of dissimilar conformations. Despite this structural plasticity, intramolecular interactions create sequence-specific structural biases that determine an IDP ensemble's three-dimensional shape. Such structural biases can be key to IDP function and are often measured in vitro, but whether those biases are preserved inside the cell is unclear. Here we show that structural biases in IDP ensembles found in vitro are recapitulated inside human-derived cells. We further reveal that structural biases can change in a sequence-dependent …
Primary Non-Function Of Hepatic Allograft With Preexisting Microvesicular Steatosis/Foamy Degeneration And Mild Large-Droplet Macrovesicular Steatosis, Melissa E Limia, Xiu Li Liu, Jennifer Yu, Kathleen Byrnes
Primary Non-Function Of Hepatic Allograft With Preexisting Microvesicular Steatosis/Foamy Degeneration And Mild Large-Droplet Macrovesicular Steatosis, Melissa E Limia, Xiu Li Liu, Jennifer Yu, Kathleen Byrnes
2020-Current year OA Pubs
It has been established that more than mild large-droplet macrovesicular steatosis (LD-MAS) is associated with increased risk of graft non-function. In contrast, even severe small-droplet macrovesicular steatosis (SD-MAS) has been found to be less prognostically significant. It remains unclear if a donor liver with diffuse microvesicular steatosis is associated with an increased risk of graft dysfunction. A 56-year-old male with alcoholic cirrhosis was transplanted with a liver from a 42-year-old overweight male donor after brain death. The frozen section of the donor liver biopsy taken at harvest showed diffusely enlarged clear/foamy hepatocytes and mild LD-MAS (about 5-10% of total tissue). …
Machine Learning-Derived Baseline Visual Field Patterns Predict Future Glaucoma Onset In The Ocular Hypertension Treatment Study, Rishabh K Singh, Sophie Smith, John Fingert, Mae Gordon, Michael Kass, Todd Scheetz, Ayellet V Segrè, Janey Wiggs, Tobias Elze, Nazlee Zebardast
Machine Learning-Derived Baseline Visual Field Patterns Predict Future Glaucoma Onset In The Ocular Hypertension Treatment Study, Rishabh K Singh, Sophie Smith, John Fingert, Mae Gordon, Michael Kass, Todd Scheetz, Ayellet V Segrè, Janey Wiggs, Tobias Elze, Nazlee Zebardast
2020-Current year OA Pubs
PURPOSE: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs).
METHODS: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS …
Calorie Restriction Reduces Biomarkers Of Cellular Senescence In Humans, Zaira Aversa, Susan B Racette, Et Al.
Calorie Restriction Reduces Biomarkers Of Cellular Senescence In Humans, Zaira Aversa, Susan B Racette, Et Al.
2020-Current year OA Pubs
Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change …
Disease Characteristics, Treatments, And Outcomes Of Patients With Pulmonary Arterial Hypertension Treated With Selexipag In Real-World Settings From The Sphere Registry (Selexipag: The Users Drug Registry), Vallerie Mclaughlin, Harrison W Farber, Kristin B Highland, Anna R Hemnes, Murali M Chakinala, Kelly M Chin, Michelle Han, Michelle Cho, Tobore Tobore, Mohammad Rahman, Nick H Kim
Disease Characteristics, Treatments, And Outcomes Of Patients With Pulmonary Arterial Hypertension Treated With Selexipag In Real-World Settings From The Sphere Registry (Selexipag: The Users Drug Registry), Vallerie Mclaughlin, Harrison W Farber, Kristin B Highland, Anna R Hemnes, Murali M Chakinala, Kelly M Chin, Michelle Han, Michelle Cho, Tobore Tobore, Mohammad Rahman, Nick H Kim
2020-Current year OA Pubs
BACKGROUND: Selexipag is an oral prostacyclin receptor agonist, indicated for pulmonary arterial hypertension to delay disease progression and reduce the risk of pulmonary arterial hypertension-related hospitalization. SelexiPag: tHe usErs dRug rEgistry (NCT03278002) was a US-based, prospective, real-world registry of selexipag-treated patients.
METHODS: Adults with pulmonary hypertension (enrolled 2016-2020) prescribed selexipag were followed for ≤18 months, with data collected at routine clinic visits. Patients were defined as newly or previously initiated if they had started selexipag ≤60 days or >60 days, respectively, before enrollment.
RESULTS: The registry included 829 patients (430 newly initiated, 399 previously initiated; 759 with pulmonary arterial hypertension), …
Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity And Inflammation In Myeloproliferative Neoplasms, Fan He, Angelo Ba Laranjeira, Tim Kong, Shuyang Lin, Katrina J. Ashworth, Alice Liu, Nina M. Lasky, Daniel Ac Fisher, Maggie J. Cox, Mary C. Fulbright, Lilian Antunes-Heck, Layow Yu, Molly Brakhane, Bei Gao, Stephen M. Sykes, Angelo D'Alessandro, Jorge Di Paola, Stephen T. Oh
Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity And Inflammation In Myeloproliferative Neoplasms, Fan He, Angelo Ba Laranjeira, Tim Kong, Shuyang Lin, Katrina J. Ashworth, Alice Liu, Nina M. Lasky, Daniel Ac Fisher, Maggie J. Cox, Mary C. Fulbright, Lilian Antunes-Heck, Layow Yu, Molly Brakhane, Bei Gao, Stephen M. Sykes, Angelo D'Alessandro, Jorge Di Paola, Stephen T. Oh
2020-Current year OA Pubs
Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we found elevated P-selectin exposure and platelet-leukocyte aggregates indicating activation of platelets from essential thrombocythemia (ET) patients. Single-cell RNA-seq analysis of primary samples revealed significant enrichment of transcripts related to platelet activation, mTOR, and oxidative phosphorylation in ET patient platelets. These observations were validated via proteomic profiling. Platelet metabolomics revealed distinct metabolic phenotypes consisting of elevated ATP generation accompanied by increases in the levels of multiple intermediates of the tricarboxylic acid cycle, but lower α-ketoglutarate (α-KG) in MPN patients. Inhibition of PI3K/AKT/mTOR signaling significantly reduced metabolic responses and …
Outcomes Of Ceftriaxone Compared With Cefazolin Or Nafcillin/Oxacillin For Outpatient Therapy For Methicillin-Sensitive Staphylococcus Aureus Bloodstream Infections: Results From A Large United States Claims Database, Yasir Hamad, Katelin B Nickel, Margaret A Olsen, Ige A George
Outcomes Of Ceftriaxone Compared With Cefazolin Or Nafcillin/Oxacillin For Outpatient Therapy For Methicillin-Sensitive Staphylococcus Aureus Bloodstream Infections: Results From A Large United States Claims Database, Yasir Hamad, Katelin B Nickel, Margaret A Olsen, Ige A George
2020-Current year OA Pubs
BACKGROUND: Ceftriaxone is a convenient option for methicillin-sensitive
METHODS: In this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models.
RESULTS: Of 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within …
Pycallingcards: An Integrated Environment For Visualizing, Analyzing, And Interpreting Calling Cards Data, Juanru Guo, Wenjin Zhang, Xuhua Chen, Allen Yen, Lucy Chen, Christian A Shively, Daofeng Li, Ting Wang, Joseph D Dougherty, Robi D Mitra
Pycallingcards: An Integrated Environment For Visualizing, Analyzing, And Interpreting Calling Cards Data, Juanru Guo, Wenjin Zhang, Xuhua Chen, Allen Yen, Lucy Chen, Christian A Shively, Daofeng Li, Ting Wang, Joseph D Dougherty, Robi D Mitra
2020-Current year OA Pubs
MOTIVATION: Unraveling the transcriptional programs that control how cells divide, differentiate, and respond to their environments requires a precise understanding of transcription factors' (TFs) DNA-binding activities. Calling cards (CC) technology uses transposons to capture transient TF binding events at one instant in time and then read them out at a later time. This methodology can also be used to simultaneously measure TF binding and mRNA expression from single-cell CC and to record and integrate TF binding events across time in any cell type of interest without the need for purification. Despite these advantages, there has been a lack of dedicated …
Concurrent Administration Of Serotonergic Antidepressants And Ozanimod In Participants With Relapsing Multiple Sclerosis From The Open-Label Extension Daybreak Trial, Robert T Naismith, Jeffrey A Cohen, Amit Bar-Or, Giancarlo Comi, Krzysztof W Selmaj, Hans-Peter Hartung, James K Sheffield, Anthony Krakovich, Daniel Tatosian, Chun-Yen Cheng, Jennifer Reardon, Vadim Khaychuk, Jon V Riolo, Diego Silva, Bruce Ac Cree
Concurrent Administration Of Serotonergic Antidepressants And Ozanimod In Participants With Relapsing Multiple Sclerosis From The Open-Label Extension Daybreak Trial, Robert T Naismith, Jeffrey A Cohen, Amit Bar-Or, Giancarlo Comi, Krzysztof W Selmaj, Hans-Peter Hartung, James K Sheffield, Anthony Krakovich, Daniel Tatosian, Chun-Yen Cheng, Jennifer Reardon, Vadim Khaychuk, Jon V Riolo, Diego Silva, Bruce Ac Cree
2020-Current year OA Pubs
BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro.
OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717).
METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using …