Digital Commons Network^™

Bleeding Assessment Tools In The Diagnosis Of Vwd In Adults And Children: A Systematic Review And Meta-Analysis Of Test Accuracy, Mohamad A. Kalot, Jorge Di Paola, Et Al

Open Access Publications

No abstract provided.

Peroxisomal Β-Oxidation Acts As A Sensor For Intracellular Fatty Acids And Regulates Lipolysis, Lianggong Ding, Wenfei Sun, Miroslav Balaz, Anyuan He, Manuel Klug, Stefan Wieland, Robert Caiazzo, Violeta Raverdy, Francois Pattou, Philippe Lefebvre, Irfan J Lodhi, Bart Staels, Markus Heim, Christian Wolfrum

Open Access Publications

To liberate fatty acids (FAs) from intracellular stores, lipolysis is regulated by the activity of the lipases adipose triglyceride lipase (ATGL), hormone-sensitive lipase and monoacylglycerol lipase. Excessive FA release as a result of uncontrolled lipolysis results in lipotoxicity, which can in turn promote the progression of metabolic disorders. However, whether cells can directly sense FAs to maintain cellular lipid homeostasis is unknown. Here we report a sensing mechanism for cellular FAs based on peroxisomal degradation of FAs and coupled with reactive oxygen species (ROS) production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed …

Genetics And Molecular Pathogenesis Of Human Hydrocephalus, Maria Garcia-Bonilla, James P. Mcallister, David D. Limbrick

Open Access Publications

No abstract provided.

Activation Of The Α1Β2Γ2l Gaba Receptor By Physiological Agonists, Spencer R Pierce, Allison L Germann, Gustav Akk

Open Access Publications

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Axicabtagene Ciloleucel As Second-Line Therapy For Large B-Cell Lymphoma, Frederick L Locke, Armin Ghobadi, Et Al

Open Access Publications

BACKGROUND: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.

METHODS: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was …

Advancing Pediatric Antimicrobial Stewardship: Has Pharmacodynamic Dosing For Gram-Negative Infections Taken Effect?, Laura M. Puckett, Jason G. Newland, Jennifer E. Girotto

Open Access Publications

No abstract provided.

Hedgehog-Interacting Protein Is A Multimodal Antagonist Of Hedgehog Signalling, Samuel C Griffiths, Rebekka A Schwab, Kamel El Omari, Benjamin Bishop, Ellen J Iverson, Tomas Malinauskas, Ramin Dubey, Mingxing Qian, Douglas F Covey, Robert J C Gilbert, Rajat Rohatgi, Christian Siebold

Open Access Publications

Hedgehog (HH) morphogen signalling, crucial for cell growth and tissue patterning in animals, is initiated by the binding of dually lipidated HH ligands to cell surface receptors. Hedgehog-Interacting Protein (HHIP), the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling, binds directly to SHH with high nanomolar affinity, sequestering SHH. Here, we report the structure of the HHIP N-terminal domain (HHIP-N) in complex with a glycosaminoglycan (GAG). HHIP-N displays a unique bipartite fold with a GAG-binding domain alongside a Cysteine Rich Domain (CRD). We show that HHIP-N is required to convey full HHIP inhibitory function, likely by interacting with the …

Regenerative Responses Of Rabbit Corneal Endothelial Cells To Stimulation By Fibroblast Growth Factor 1 (Fgf1) Derivatives, Tthx1001 And Tthx1114, Jessica Weant, David D Eveleth, Amuthakannan Subramaniam, Jennifer Jenkins-Eveleth, Michael Blaber, Ling Li, David M Ornitz, Asaf Alimardanov, Trevor Broadt, Hui Dong, Vinay Vyas, Xiaoyi Yang, Ralph A Bradshaw

Open Access Publications

Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC

Lyl-1 Regulates Primitive Macrophages And Microglia Development, Shoutang Wang, Deshan Ren, Brahim Arkoun, Anna-Lila Kaushik, Gabriel Matherat, Yann Lécluse, Dominik Filipp, William Vainchenker, Hana Raslova, Isabelle Plo, Isabelle Godin

Open Access Publications

During ontogeny, macrophage populations emerge in the Yolk Sac (YS) via two distinct progenitor waves, prior to hematopoietic stem cell development. Macrophage progenitors from the primitive/"early EMP" and transient-definitive/"late EMP" waves both contribute to various resident primitive macrophage populations in the developing embryonic organs. Identifying factors that modulates early stages of macrophage progenitor development may lead to a better understanding of defective function of specific resident macrophage subsets. Here we show that YS primitive macrophage progenitors express Lyl-1, a bHLH transcription factor related to SCL/Tal-1. Transcriptomic analysis of YS macrophage progenitors indicate that primitive macrophage progenitors present at embryonic day …

Asthma Reduces Glioma Formation By T Cell Decorin-Mediated Inhibition Of Microglia, Jit Chatterjee, Shilpa Sanapala, Olivia Cobb, Alice Bewley, Andrea K Goldstein, Elizabeth Cordell, Xia Ge, Joel R Garbow, Michael J Holtzman, David H Gutmann

Open Access Publications

To elucidate the mechanisms underlying the reduced incidence of brain tumors in children with Neurofibromatosis type 1 (NF1) and asthma, we leverage Nf1 optic pathway glioma (Nf1

Immunosuppression And Outcomes In Adult Patients With De Novo Acute Myeloid Leukemia With Normal Karyotypes, Francesca Ferraro, Christopher A Miller, Keegan A Christensen, Nichole M Helton, Margaret O'Laughlin, Catrina C Fronick, Robert S Fulton, Jessica Kohlschmidt, Ann-Kathrin Eisfeld, Clara D Bloomfield, Sai Mukund Ramakrishnan, Ryan B Day, Lukas D Wartman, Geoffrey L Uy, John S Welch, Matthew J Christopher, Sharon E Heath, Jack D Baty, Matthew J Schuelke, Jacqueline E Payton, David H Spencer, Michael P Rettig, Daniel C Link, Matthew J Walter, Peter Westervelt, John F Dipersio, Timothy J Ley

Open Access Publications

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; >5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic studies, we characterized 28 normal karyotype (NK)-AML patients with >5 y first remissions after chemotherapy (LFRs) and compared them to a well-matched group of 31 NK-AML patients who relapsed within 2 y (standard first remissions [SFRs]). Our combined analyses indicated that genetic-risk profiling at presentation (as defined by European …

High-Throughput Functional Analysis Of Cftr And Other Apically Localized Proteins In Ipsc-Derived Human Intestinal Organoids, Sunny Xia, Zoltán Bozóky, Michelle Di Paola, Onofrio Laselva, Saumel Ahmadi, Jia Xin Jiang, Amy L Pitstick, Chong Jiang, Daniela Rotin, Christopher N Mayhew, Nicola L Jones, Christine E Bear

Open Access Publications

Induced Pluripotent Stem Cells (iPSCs) can be differentiated into epithelial organoids that recapitulate the relevant context for CFTR and enable testing of therapies targeting Cystic Fibrosis (CF)-causing mutant proteins. However, to date, CF-iPSC-derived organoids have only been used to study pharmacological modulation of mutant CFTR channel activity and not the activity of other disease-relevant membrane protein constituents. In the current work, we describe a high-throughput, fluorescence-based assay of CFTR channel activity in iPSC-derived intestinal organoids and describe how this method can be adapted to study other apical membrane proteins. Specifically, we show how this assay can be employed to study …

A Deep Learning Framework Identifies Dimensional Representations Of Alzheimer's Disease From Brain Structure, Zhijian Yang, Ilya M. Nasrallah, John C. Morris, Et Al

Open Access Publications

No abstract provided.

Gene Dosage Effects Of Poly(A) Track-Engineered Hypomorphs, Geralle Powell, Slavica Pavlovic Djuranovic, Sergej Djuranovic

Open Access Publications

Manipulation of gene activity through creation of hypomorphic mutants has been a long-standing tool in examining gene function. Our previous studies have indicated that hypomorphic mutants could be created by inserting

Using Nasal Povidone-Iodine To Prevent Bloodstream Infections And Transmission Of Staphylococcus Aureus Among Haemodialysis Patients: A Stepped-Wedge Cluster Randomised Control Trial Protocol, Ana-Monica Racila, Amy O'Shea, Rajeshwari Nair, Kimberly Dukes, Loreen Herwaldt, Linda Boyken, Daniel Diekema, Melissa Ward, Jason Cobb, Jesse Jacob, David Pegues, Susan Bleasdale, Anitha Vijayan, Anubha Mutneja, Mony Fraer, Debra O'Connell-Moore, Pam Tolomeo, Minerva Mendez, Erin Jaworski, Marin Schweizer

Open Access Publications

INTRODUCTION: Approximately 38% of haemodialysis patients carry

METHODS AND ANALYSIS: We will perform an open-label, stepped-wedge cluster randomised trial to assess the effectiveness of nasal PVI compared with standard care. Sixteen outpatient haemodialysis units will participate in the study. The 3-year trial period will be divided into a 4-month baseline period and eight additional 4-month time blocks. The primary outcome of the study will be

ETHICS AND DISSEMINATION: This study has received IRB approval from all study sites. A Data Safety and Monitoring Board will monitor this multicentre clinical trial. We will present our results at international meetings. The study …

Social Needs, Chronic Conditions, And Health Care Utilization Among Medicaid Beneficiaries, Amy Mcqueen, Linda Li, Cynthia J. Herrick, Niko Verdecias, Derek S. Brown, Darrell J. Broussard, Rachel E. Smith, Matthew Kreuter

Open Access Publications

No abstract provided.

Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: Interim Analysis Of The Phase 2 Pathfinder Trial, Jason Gotlib, Andreas Reiter, Stephen T Oh, Et Al

Open Access Publications

Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase 2 trial (no. NCT03580655 ) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200 mg in patients with AdvSM (n = 62). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM-Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes …

Fabrication And Evaluation Of Bilateral Helmholtz Radiofrequency Coil For Thermo-Stable Breast Image With Reduced Artifacts, Young Han Lee, Kyu-Ho Song, Jaemoon Yang, Won Jun Kang, Keum Sil Lee, Min Jung Kim, Eun-Kyung Kim, Dan Heo, Bo-Young Choe, Jin-Suck Suh

Open Access Publications

PURPOSE: The positron emission tomography (PET)-magnetic resonance (MR) system is a newly emerging technique that yields hybrid images with high-resolution anatomical and metabolic information. With PET-MR imaging, a definitive diagnosis of breast abnormalities will be possible with high spatial accuracy and images will be acquired for the optimal fusion of anatomic locations. Therefore, we propose a PET-compatible two-channel breast MR coil with minimal disturbance to image acquisition which can be used for simultaneous PET-MR imaging in patients with breast cancer.

MATERIALS AND METHODS: For coil design and construction, the conductor loops of the Helmholtz coil were tuned, matched, and subdivided …

Access To And Safety Of Covid-19 Convalescent Plasma In The United States Expanded Access Program: A National Registry Study, Jonathon W. Senefeld, Brenda J. Grossman, Et Al

Open Access Publications

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma.

METHODS AND FINDINGS: Mayo Clinic served as the central …

Minimizing The Impact Of The Triple Burden Of Covid-19, Tuberculosis And Hiv On Health Services In Sub-Saharan Africa, Jean B Nachega, Nathan Kapata, Nadia A Sam-Agudu, Eric H Decloedt, Patrick D M C Katoto, Tumaini Nagu, Peter Mwaba, Dorothy Yeboah-Manu, Pascalina Chanda-Kapata, Francine Ntoumi, Elvin H Geng, Alimuddin Zumla

Open Access Publications

In this perspective, we discuss the impact of COVID-19 on tuberculosis (TB)/HIV health services and approaches to mitigating the growing burden of these three colliding epidemics in sub-Saharan Africa (SSA). SSA countries bear significantly high proportions of TB and HIV cases reported worldwide, compared to countries in the West. Whilst COVID-19 epidemiology appears to vary across Africa, most countries in this region have reported relatively lower-case counts compared to the West. Nevertheless, the COVID-19 pandemic has added an additional burden to already overstretched health systems in SSA, which, among other things, have been focused on the longstanding dual epidemics of …

Temporal Evolution Of The Pcvco2–Paco2/Cao2–Ccvo2 Ratio Vs Serum Lactate During Resuscitation In Septic Shock, Shyam Madabhushi, Anjan Trikha, Rahul K. Anand, Rashmi Ramachandran, Preet M. Singh, Vimi Rewari

Open Access Publications

No abstract provided.

Kinetic And Structural Mechanism For Dna Unwinding By A Non-Hexameric Helicase, Sean P. Carney, Wen Ma, Kevin D. Whitley, Haifeng Jia, Timothy M. Lohman, Zaida Luthey-Schulten, Yann R. Chemla

Open Access Publications

No abstract provided.

Investigating Late-Onset Pompe Prevalence In Neuromuscular Medicine Academic Practices, Marie Wencel, Alan Pestronk, Julaine Florence, Et Al

Open Access Publications

No abstract provided.

Trajectory Of Emotion Dysregulation In Positive And Negative Affect Across Childhood Predicts Adolescent Emotion Dysregulation And Overall Functioning, Alecia C. Vogel, Rebecca Tillman, Nourhan M. El-Sayed, Joshua J. Jackson, Susan B. Perlman, Deanna M. Barch, Joan L. Luby

Open Access Publications

No abstract provided.

Compositional Analysis Of Extracellular Aggregates In The Eyes Of Patients With Exfoliation Syndrome And Exfoliation Glaucoma, Alicia De Maria, Keith D Zientek, Larry L David, Phillip A Wilmarth, Anjali M Bhorade, George J Harocopos, Andrew J W Huang, Augustine R Hong, Carla J Siegfried, Linda M Tsai, Arsham Sheybani, Steven Bassnett

Open Access Publications

Purpose: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals.

Methods: Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry …

Prediction Of Chronic Postsurgical Pain In Adults: A Protocol For Multivariable Prediciton Model Development, Nicholas Papadomanolakis-Pakis, Simon Haroutounian, Christian Christiansen, Lone Nikolajsen

Open Access Publications

No abstract provided.

Long-Term Outcomes Of Primary Cardiac Malignant Tumors: Difference Between African American And Caucasian Population, Quoc Bui, Tam N M Ngo, Jan Mazur, Vy Pham, Cassady Palmer, Binh Q Truong, Eugene S Chung, Huy G Vuong, Vien T Truong

Open Access Publications

BACKGROUND: The survival outcome for primary cardiac malignant tumors (PMCTs) based on race has yet to be fully elucidated in previously published literature. This study aimed to address the general long-term outcome and survival rate differences in PMCTs among African Americans and Caucasian populations.

METHODS: The 18 cancer registries database from the Surveillance, Epidemiology, and End Results (SEER) Program from 1975 to 2016 were utilized. Ninety-four African American (AA) and 647 Caucasian (CAU) patients from the SEER registry were available for survival analysis. The log-rank test was used to compare the difference in mortality between two populations and presented by …

Demographic And Mental Health Assessments In The Adolescent Brain And Cognitive Development Study: Updates And Age-Related Trajectories, Deanna M Barch, Nicole R Karcher, Et Al

Open Access Publications

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for …

How The Value Of The Environment Controls Persistence In Visual Search, Michael R. Traner, Ethan S. Bromberg-Martin, Ilya E. Monosov

Open Access Publications

Classic foraging theory predicts that humans and animals aim to gain maximum reward per unit time. However, in standard instrumental conditioning tasks individuals adopt an apparently suboptimal strategy: they respond slowly when the expected value is low. This reward-related bias is often explained as reduced motivation in response to low rewards. Here we present evidence this behavior is associated with a complementary increased motivation to search the environment for alternatives. We trained monkeys to search for reward-related visual targets in environments with different values. We found that the reward-related bias scaled with environment value, was consistent with persistent searching after …

Neutrophil Extracellular Trap Inhibition Increases Inflammation, Bacteraemia And Mortality In Murine Necrotizing Enterocolitis, Hala Chaaban, Kathryn Burge, Jeffrey Eckert, Ravi S Keshari, Robert Silasi, Cristina Lupu, Barbara Warner, Marilyn Escobedo, Michael Caplan, Florea Lupu

Open Access Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease affecting primarily premature infants. The disease is characterized by intestinal inflammation and leucocyte infiltration, often progressing to necrosis, perforation, systemic inflammatory response and death. Neutrophil extracellular traps (NETs), denoting nuclear DNA, histone and antimicrobial protein release, have been suggested to play a role in NEC. This study aimed to determine the role of NETs in NEC and explore the effect of chloramidine, a NET inhibitor, on a murine NEC-like intestinal injury model. Blood and intestinal tissues were collected from infants diagnosed with ≥ Stage II NEC, and levels of nucleosomes and NETs, …