tbuckley/cabot-search huggingface dataset:
Abstract 15736: The Sphk1/s1p Signaling Axis Regulates Pulmonary Vascular Inflammation by Activating Nf-kb and Nlrp3 Inflammasome
Authors: Yang Bai, Alan de Brito Carneiro, Angelia Lockett, Marta T Gomes, Nicole Jones, Yen Chun Lai, Roberto F MacHado
Journal: Circulation (2020)

Rationale: Pulmonary vascular inflammation is activated during the development of pulmonary arterial hypertension (PAH). Sphingosine kinase 1 (Sphk1) catalyzes the formation of sphingosine-1-phosphate (S1P), which has been shown to promote inflammation by activating nuclear factor kappa B (NF-κB) and the nucleotide oligomerization domain-like receptor 3 (NLRP3) inflammasome. However, the impact of S1P on NLRP3 inflammasome activation in PAH is unknown. Here, we tested whether Sphk1/S1P regulates pulmonary vascular inflammation via activating NF-κB and the NLRP3 inflammasome. Methods: Human pulmonary arterial smooth muscle cells (PASMCs) and endothelial cells (PAECs) were treated with S1P or were exposed to hypoxia. Sphk1 plasmid or siRNA was used to increase and decrease Sphk1/S1P levels, respectively. Activation of NF-κB signaling and the NLRP3 inflammasome (increased NLRP3, cleaved caspase-1, IL-1β and IL-18) were detected by western blots or real-time PCR. ELISA was used to measure secretion of IL-1β. Results: S1P treatment led to a biphasic phosphorylation and degradation of IκBα accompanied by increased phosphorylation and expression of NF-κB in PASMCs. S1P treatment also resulted in increased expression of inflammasome mediators, NLRP3 and cleaved caspase-1, enhanced intracellular expression of IL-1b and IL-18, and higher levels of secreted IL-1β compared to controls. Notably, over expression of Sphk1 in PASMCs led to increased NF-κB and NLRP3 expression, whereas suppression of Sphk1 expression reduced NLRP3, cleavage of IL-1β and IL-18 expression and phosphorylation of NF-κB. Similar phenomena with respect to inflammasome activation and IL-1β secretion was observed in PASMCs exposed to hypoxia. Increased NF-κB and NLRP3 activation, cleavage of caspase-1 were also observed in S1P treated PAECs, however no changes in IL-1β secretion levels were detected. Conclusion: These findings suggest that S1P induces pulmonary vascular pro-inflammatory signaling via activation of NF-κB and the NLRP3 inflammasome, and that the S1P/Sphk1 signaling axis may be involved in this context. Activation of the inflammasome may be an important mechanism underlying PAH pathogenesis, targeting of which may be exploited for the treatment of PAH.
An <i>in vitro</i> model using spheroids-laden nanofibrous structures for attaining high degree of myoblast alignment and differentiation
Authors: Miji Yeo, SooJung Chae, GeunHyung Kim
Journal: Theranostics (2021)

A spheroid is an aggregation of single cells with structural and functional characteristics similar to those of 3D native tissues, and it has been utilized as one of the typical in vitro three-dimensional (3D) cell models. Scaffold-free spheroids provide outstanding reflection of tissue complexity in a 3D in vivo-like environment, but they can neither fabricate realistic macroscale 3D complex structures without avoiding necrosis nor receive direct external stimuli (i.e., stimuli from mechanical or topographical cues). Here, we propose a spheroid-laden electrospinning process to obtain in vitro model achieved using the synergistic effect of the unique bioactive components provided by the spheroids and stimulating effects provided by the aligned nanofibers. Methods: To show the functional activity of the spheroid-laden structures, we used myoblast-spheroids to obtain skeletal muscle, comprising highly aligned myotubes, utilizing an uniaxially arranged topographical cue. The spheroid-electrospinning was used to align spheroids directly by embedding them in aligned alginate nanofibers, which were controlled with various materials and processing parameters. Results: The spheroids laden in the alginate nanofibers showed high cell viability (>90%) and was compared with that of a cell-laden alginate nanofiber that was electrospun with single cells. Consequently, the spheroids laden in the aligned nanofibers showed a significantly higher degree of myotube formation and maturation. Conclusion: Results suggested that the in vitro model using electrospun spheroids could potentially be employed to understand myogenic responses for various in vitro drug tests.
Viral Loads of SARS-CoV-2 in Young Children
Authors: Julie C. Dunning Hotopp
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 190: Continuous Vascular Remodeling Related To Development Of Arteriosclerosis Or Atherosclerosis In Kawasaki Disease ~ Immunohistochemical Study using an Animal Model ~
Authors: Kenji Hamaoka, Maiko Fujii, Yuki Kuchitsu, Ayako Yoshioka, Akiko Okamoto, Chinatsu Suzuki, Tomoyo Yahata, Akihiro Nakamura, Kazuyuki Ikeda
Journal: Circulation (2015)

Background: Atherosclerotic coronary heart disease has recently emerged as a clinical issue among young individuals with a history of Kawasaki disease (KD), which is a systemic vasculitis unique to children. However, whether or not and how KD promotes atherosclerosis remains unclear. We hypothesized that, analogous to the pathogenesis of arteriosclerosis or atherosclerosis, endothelial injury and the resultant intimal thickening are induced in coronary arteries after attenuation of vasculitis. Methods: We used a rabbit model of KD developed by Onouchi et al. and performed histopathological analysis of the coronary arteries at acute (1, 3, 5, and 7 days) and chronic (3 months) phases of the disease. Results: In these rabbit models, a pan-arteritis with significant intimal cellular hypertrophy was histologically detected in the acute phase, and arterial intimal thickening was observed during the chronic phase. Immunohistochemical analysis of the coronary arteries revealed that the thickened intimal lesions observed during the chronic phase comprised abundant α-smooth muscle actin (α-SMA)-positive cells, most of which concomitantly expressed vascular cell adhesion molecule-1 and nuclear factor-κB. Although macrophages positive for RAM11 were barely detected, macrophage colony stimulating factor was strongly expressed in migrating smooth muscle cells in the intimal layer. In addition, the accumulation of proteoglycan as extracellular matrix was distinctly visible in the thickened intima, indicating progressive accumulation of lipids and proliferation of smooth muscle cells within the lesion. Conclusions: These findings suggest that, in KD-associated vasculitis, the migration of α-SMA-positive cells into the thickened intima might induce continuous vascular inflammation and remodeling, which might progress to coronary arteriosclerosis or atherosclerosis.
Allergological evaluation of hypersensitivity drug reactions to betalactams in children
Authors: Isabel Torres Rojas, Ana Prieto-Moreno, Maria Desamparados Cervera, Diana Pérez-Alzate, Francisco Javier Ruano, Maria Luisa Somoza Álvarez, Paula López-González, María Vázquez De La Torre, Elisa Haroun-Díaz, Natalia Blanca-López, Gabriela Canto
Journal: Journal of Allergy and Clinical Immunology (2021)
Covid-19: New data on Oxford AstraZeneca vaccine backs 12 week dosing interval
Authors: Jacqui Wise
Journal: BMJ (2021)

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Diverse Eukaryotic CGG-Binding Proteins Produced by Independent Domestications of<i>hAT</i>Transposons
Authors: Isaac Yellan, Ally W H Yang, Timothy R Hughes
Journal: Molecular Biology and Evolution (2021)

The human transcription factor (TF) CGGBP1 (CGG-binding protein) is conserved only in amniotes and is believed to derive from the zf-BED and Hermes transposase DNA-binding domains (DBDs) of a hAT DNA transposon. Here, we show that sequence-specific DNA-binding proteins with this bipartite domain structure have resulted from dozens of independent hAT domestications in different eukaryotic lineages. CGGBPs display a wide range of sequence specificity, usually including preferences for CGG or CGC trinucleotides, whereas some bind AT-rich motifs. The CGGBPs are almost entirely nonsyntenic, and their protein sequences, DNA-binding motifs, and patterns of presence or absence in genomes are uncharacteristic of ancestry via speciation. At least eight CGGBPs in the coelacanth Latimeria chalumnae bind distinct motifs, and the expression of the corresponding genes varies considerably across tissues, suggesting tissue-restricted function.
The tripartite insurance model (TIM): a financial incentive to prevent outbreaks of infections due to multidrug-resistant microorganisms in hospitals
Authors: Simon van der Pol, Jan-Willem H. Dik, Corinna Glasner, Maarten J. Postma, Bhanu Sinha, Alex W. Friedrich
Journal: Clinical Microbiology and Infection (2021)

Healthcare-associated infections caused by multidrug-resistant organisms (MDROs) constitute a major challenge worldwide, but care providers are often not sufficiently incentivized to implement recommended infection prevention measures to prevent the spread of such infections. We propose a new approach which creates incentives for hospitals, external laboratories and insurers to collaborate on preventing MDRO outbreaks by testing more and implementing infection prevention measures. This tripartite insurance model (TIM) redistributes the costs of preventing and combating MDRO outbreaks in a way that all parties benefit from reducing the number of outbreaks.
IDSA made 4 strong recommendations for preventing COVID-19 infection in health care personnel
Authors: Siddharth P. Dugar, Saraschandra Vallabhajosyula
Journal: Annals of Internal Medicine (2021)

Source CitationLynch JB, Davitkov P, Anderson DJ, et al. Infectious Diseases Society of America guidelines on infection prevention for health care personnel caring for patients with suspected or known COVID-19. Clin Infect Dis. 2020. [Epub ahead of print.] https://pubmed.ncbi.nlm.nih.gov/32716496/AbstractClinical Impact RatingsEmergency Med: Cardiology: Nephrology:
Immune signatures distinguish frequent from non‐frequent exacerbators among children with severe asthma
Authors: Karine Adel‐Patient, Marta Grauso, Rola Abou‐Taam, Blanche Guillon, Céline Dietrich, François Machavoine, Nicolas Garcelon, Mélanie Briard, Hassan Faour, Antoine Neuraz, Christophe Delacourt, Thierry J. Molina, Maria Leite‐de‐Moraes, Guillaume Lezmi
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
CAPTAIN: Effects of Body Mass Index (BMI) on Response to Triple Therapy in Patients With Inadequately Controlled Asthma on Inhaled Corticosteroids/Long-acting β2-agonists (ICS/LABA)
Authors: Diego Maselli, Sarah Chang, Andrew Fowler, Mark Liu, Michael Manning, David Mannino, Joseph Spahn, Agne Zarankaite, Edward Kerwin
Journal: Journal of Allergy and Clinical Immunology (2021)
Neurothreads: Development of supportive carriers for mature dopaminergic neuron differentiation and implantation
Authors: Aleksandra Filippova, Fabien Bonini, Liudmila Efremova, Manon Locatelli, Olivier Preynat-Seauve, Amélie Béduer, Karl-Heinz Krause, Thomas Braschler
Journal: Biomaterials (2021)

In this study we present the use of elastic macroporous cryogels for differentiation and transplantation of mature neurons. We develop a coating suitable for long-term neuronal culture, including stem cell differentiation, by covalent immobilization of neural adhesion proteins. In the context of cell therapy for Parkinson's disease, we show compatibility with established dopaminergic differentiation of both immortalized mesencephalic progenitors - LUHMES - and human embryonic stem cells (hESCs). We adjust structural properties of the biomaterial to create carriers - Neurothreads - favourable for cell viability during transplantation. Finally, we show feasibility of preservation of mature neurons, supported by Neurothreads, one month after in-vivo transplantation. Preliminary data suggests that the Neurothread approach could provide more mature and less proliferative cells in vivo.
Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non–Clear Cell Renal Cell Carcinoma
Authors: David F. McDermott, Jae-Lyun Lee, Marek Ziobro, Cristina Suarez, Przemyslaw Langiewicz, Vsevolod Borisovich Matveev, Pawel Wiechno, Rustem Airatovich Gafanov, Piotr Tomczak, Frederic Pouliot, Frede Donskov, Boris Yakovlevich Alekseev, Sang Joon Shin, Georg A. Bjarnason, Daniel Castellano, Rachel Kloss Silverman, Rodolfo F. Perini, Charles Schloss, Michael B. Atkins
Journal: Journal of Clinical Oncology (2021)

Programmed death 1 (PD-1) pathway inhibitors have not been prospectively evaluated in patients with non-clear cell renal cell carcinoma (nccRCC). The phase II KEYNOTE-427 study (cohort B) was conducted to assess the efficacy and safety of single-agent pembrolizumab, a PD-1 inhibitor, in advanced nccRCC.
Abstract P206: Control of Cardiovascular Risk Factors among Diabetic Patients in an Outpatient Setting
Authors: Ariel T Holland, Beinan Zhao, Eric C Wong, Sarah Choi, Nathan D Wong, Latha P Palaniappan
Journal: Circulation (2012)

Background: Previous studies have shown that cardiovascular risk factors among Hispanic and Black patients with type 2 diabetes are poorly controlled, but no studies have been conducted in Asian American populations. Objective: To examine racial/ethnic differences in control of cardiovascular risk factors in patients with type 2 diabetes across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese), compared to Non-Hispanic Whites (NHWs) in a multi-specialty healthcare organization in California. Methods: Electronic health records of 12,804 active primary care Asian American (n=4,594) and NHW (n=8,210) patients, ages 35 years and older, with type 2 diabetes were examined from 2007-2009. Diabetes was classified through ICD-9 codes, abnormal laboratory values, or use of anti-diabetic medications. Sex-age directly standardized prevalence rates and multivariate adjusted odds ratios (OR) were calculated for attainment of the following cardiovascular risk factor goals: glycosylated hemoglobin (A1C) &lt; 7%, blood pressure (BP) &lt; 130/80 mmHg, and low-density lipoprotein cholesterol (LDL-C) &lt; 100 mg/dL, and simultaneous control (A1C, BP, and LDL-C). ORs were calculated accounting for race/ethnicity, age, sex, BMI, insurance, and number of clinic visits. Results: The ranges of standardized goal attainment rates among Asian American subgroups and NHWs were as follows: A1C (58.5% in Filipinos to 75.3% in Vietnamese), BP (39.9% in Vietnamese to 53.4% in Chinese), LDL-C (50.3% in Koreans to 65.5% in Asian Indians), and simultaneous control (18.1% in Filipinos to 24.8% in Chinese). After adjusting for patient characteristics, Asian Americans had significantly lower odds of A1C goal attainment (OR=0.76, 95% CI: 0.69-0.85), and higher odds of LDL-C goal attainment (1.17, 1.05-1.29), compared to NHWs. Among Asian subgroups, Asian Indians, Filipinos, Japanese and Koreans had significantly lower odds of goal attainment for A1C, compared to NHWs. Asian Indians (OR= 1.15, 95% CI: 1.01-1.32) and Chinese (1.28, 1.12-1.46) had significantly higher odds of goal attainment for BP, compared to NHWs. Odds of LDL-C goal attainment were also significantly higher for Asian Indians (1.29, 1.11-1.49) and Filipinos (1.19, 1.01-1.39), compared to NHWs. Conclusion: Among our type 2 diabetes patients, Asian Americans have worse control of A1C, despite better control of LDL-C and BP, compared to NHWs. There is also significant heterogeneity in control of cardiovascular risk factors among Asian American subgroups. Optimal simultaneous goal attainment was seen in a small proportion of diabetes patients. Achieving goals for cardiovascular risk factors is difficult and health care providers may need to alter their treatment focus for different racial/ethnic groups.
Nanoluciferase complementation-based bioreporter reveals the importance of N-linked glycosylation of SARS-CoV-2 S for viral entry
Authors: Taha Azad, Ragunath Singaravelu, Zaid Taha, Taylor R. Jamieson, Stephen Boulton, Mathieu J.F. Crupi, Nikolas T. Martin, Emily E.F. Fekete, Joanna Poutou, Mina Ghahremani, Adrian Pelin, Kazem Nouri, Reza Rezaei, Christopher Boyd Marshall, Masahiro Enomoto, Rozanne Arulanandam, Nouf Alluqmani, Reuben Samson, Anne-Claude Gingras, D. William Cameron, Peter A. Greer, Carolina S. Ilkow, Jean-Simon Diallo, John C. Bell
Journal: Molecular Therapy (2021)

The ongoing COVID-19 pandemic has highlighted the immediate need for the development of antiviral therapeutics targeting different stages of the SARS-CoV-2 life cycle. We developed a bioluminescence-based bioreporter to interrogate the interaction between the SARS-CoV-2 viral spike (S) protein and its host entry receptor, angiotensin-converting enzyme 2 (ACE2). The bioreporter assay is based on a nanoluciferase complementation reporter, composed of two subunits, large BiT and small BiT, fused to the S receptor-binding domain (RBD) of the SARS-CoV-2 S protein and ACE2 ectodomain, respectively. Using this bioreporter, we uncovered critical host and viral determinants of the interaction, including a role for glycosylation of asparagine residues within the RBD in mediating successful viral entry. We also demonstrate the importance of N-linked glycosylation to the RBD's antigenicity and immunogenicity. Our study demonstrates the versatility of our bioreporter in mapping key residues mediating viral entry as well as screening inhibitors of the ACE2-RBD interaction. Our findings point toward targeting RBD glycosylation for therapeutic and vaccine strategies against SARS-CoV-2.
Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer
Authors: Adam C. Mueller, Miles Piper, Andrew Goodspeed, Shiv Bhuvane, Jason S. Williams, Shilpa Bhatia, Andy V. Phan, Benjamin Van Court, Kathryn L. Zolman, Brisa Peña, Ayman J. Oweida, Sara Zakem, Cheryl Meguid, Michael W. Knitz, Laurel Darragh, Thomas E. Bickett, Jacob Gadwa, Luisa Mestroni, Matthew R.G. Taylor, Kimberly R. Jordan, Peter Dempsey, M. Scott Lucia, Martin D. McCarter, Marco Del Chiaro, Wells A. Messersmith, Richard D. Schulick, Karyn A. Goodman, Michael J. Gough, Casey S. Greene, James C. Costello, Antonio Galveo Neto, David Lagares, Kirk C. Hansen, Adrie Van Bokhoven, Sana D. Karam
Journal: Cancer Research (2021)

Abstract Stromal fibrosis activates prosurvival and proepithelial-to-mesenchymal transition (EMT) pathways in pancreatic ductal adenocarcinoma (PDAC). In patient tumors treated with neoadjuvant stereotactic body radiation therapy (SBRT), we found upregulation of fibrosis, extracellular matrix (ECM), and EMT gene signatures, which can drive therapeutic resistance and tumor invasion. Molecular, functional, and translational analysis identified two cell-surface proteins, a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, as drivers of fibrosis and tumor progression after radiation therapy (RT). RT resulted in increased ADAM10 expression in tumor cells, leading to cleavage of ephrinB2, which was also detected in plasma. Pharmacologic or genetic targeting of ADAM10 decreased RT-induced fibrosis and tissue tension, tumor cell migration, and invasion, sensitizing orthotopic tumors to radiation killing and prolonging mouse survival. Inhibition of ADAM10 and genetic ablation of ephrinB2 in fibroblasts reduced the metastatic potential of tumor cells after RT. Stimulation of tumor cells with ephrinB2 FC protein reversed the reduction in tumor cell invasion with ADAM10 ablation. These findings represent a model of PDAC adaptation that explains resistance and metastasis after RT and identifies a targetable pathway to enhance RT efficacy. Significance: Targeting a previously unidentified adaptive resistance mechanism to radiation therapy in PDAC tumors in combination with radiation therapy could increase survival of the 40% of PDAC patients with locally advanced disease. See related commentary by Garcia Garcia et al., p. 3158
Abstract 14041: Impact of Tricuspid Regurgitation and Surgical Intervention for Tricuspid Regurgitation Across Staged Palliation for Single Right Ventricle Anomalies: The Single Ventricle Reconstruction Trial
Authors: James F Cnota, Shahryar M Chowdhury, Alejandro Floh, Russell Gongwer, Benjamin Goot, Jeffrey P Jacobs, Matthew Jolley, Sonya Kirmani, Damien LaPar, Jami C Levine, Alan B Lewis, Ricardo H Pignatelli, Christian Pizarro, Tim C Slesnick, Thor Thorsson, Felicia Trachtenberg, Dongngan Truong, Jane W Newburger, Peter C Frommelt
Journal: Circulation (2019)

Introduction: Tricuspid regurgitation (TR) is common in single right ventricle (RV) and affects outcomes of staged palliation. However, longitudinal studies are limited, and the impact of tricuspid...