tbuckley/cabot-search huggingface dataset:
Urokinase receptor (uPAR) regulates ovarian cancer cell adhesion to fibronectin through interaction with alpha5beta1 integrin
Authors: Ying Wei, Liliane Robillard, Matthias C. Kugler, Feng Zhang, Kevin K. Kim, Harold A. Chapman
Journal: Cancer Research (2005)

3759  Epithelial ovarian carcinoma is a highly lethal tumor due to its propensity to form widespread peritoneal implants throughout the abdominal cavity. The understanding of the molecular mechanisms in which ovarian carcinoma implants attach to mesothelium may permit the development of strategies that limit the intra-abdominal tumor spread. It has been reported that beta1-integrin adhesion receptors are widely expressed by ovarian cancer cells and are largely responsible for mediating mesothelial binding through recognition of mesothelial-associated extracellular matrix proteins (ECM), such as fibronectin (Fn) (apha5beta1), laminin-5 (alpha3beta1), and collagen (alpha2beta1). Fibronectin receptor alpha5beta1 has been found to play a key role in ovarian cancer cell adhesion to peritoneal mesothelium in vitro using neutralizing integrin antibodies. The main focus of this study is to investigate how alpha5beta1-mediated Fn adhesion is regulated in ovarian cancer cells. We and others have previously shown that beta1 integrin function can be regulated by urokinase receptors (uPAR), GPI-anchored membrane proteins upregulated during tumor progression, associate with beta1 integrins, and localizing urokinase to sites of cell attachment. Recently we found uPAR directly binds alpha5beta1 integrin and renders Fn binding by alpha5beta1 Arg-Gly-Asp (RGD) resistant. FACS analysis and Western blotting detected cell surface expression of alpha5beta1 integrin and uPAR in human ovarian cancer Skov-3 cells. Fn adhesion of these cells is RGD-resistant and mainly alpha5beta1-mediated because it can be completely blocked by alpha5-blocking antibodies. Suppression of endogenous uPAR by RNA interference in Skov-3 cells resulted in weaker, RGD-sensitive Fn adhesion and altered overall alpha5beta1 conformation detected by LIBS antibodies (HUTS-21 and 9EG7). Interestingly, beta1 peptides that disrupt uPAR/alpha5beta1 association inhibited Skov-3 adhesion to Fn. Taken together, uPAR/alpha5beta1 complex may be responsible for fibronectin-mediated ovarian cancer binding to mesothelium. Because ovarian cancer cell binding to peritoneal mesothelium is mediated by several adhesion pathways, some are RGD-sensitive and some are RGD-resistant, simultaneous inhibition of both uPAR/beta1 integrin (by beta1 peptides) and other integrins (such as alphavbeta3 by RGD peptides) may lead to the significant limit of the intra-abdominal spread of this tumor in vivo.
Abstract 16509: Incidence, Risk Factors and Prognostic Implications of Covid-19 St-segment Elevation Across a Large Health System in New York
Authors: Arvind Devanabanda, Eitezaz Mahmood, Ibrahim Ali, Avneet SINGH, Perwaiz Meraj, rajiv jauhar
Journal: Circulation (2020)

Introduction: There is limited evidence on ST elevation myocardial Infarction (STEMI) in COVID-19 patients. The aim of this study is to demonstrate the incidence of STEMI, clinical and angiographic outcomes, risk factors of COVID-19 patients among focal STEMIs, diffuse ST-elevation (STE), and no-STE. Methods: We retrospectively identified COVID-19 patients at 13 different hospitals from March 1 to April 30, 2020. All ECGs were analyzed for focal, diffuse or no-STE. Outcomes examined were death, ventilation, ICU admission, pressor and inotrope use and length of stay. Kaplan-Meier method estimated cumulative probability of death by STEMI status. Multivariate regression analysis identified association of STEMI and death. Results: There were 10,018 patients with 23,406 ECGs, of which 55 (0.5%) had focal STE, 22 (0.2%) had diffuse STE and 9,945 patients had no-STE. Death, length of stay, ICU stay, ventilator use, inotrope use, and pressor use were all statistically significant (p&lt;0.0001) among no-STE, focal STE and diffuse STE groups. Cardiac catheterization performed on 10 STE patients, showed culprit lesions were left anterior descending artery 30%, right coronary artery 40% and no obstructive disease 30% of the time. Median symptom onset to ER presentation time in COVID STEMI was 12 hours. Figure 1 demonstrates the overall survival rates of 31%, 33%, and 6% in the no-STE, diffuse STE, and focal STE group, respectively ( P &lt; .0001). Table 1 shows the strongest cardiac and ECG predictors of death in COVID-19 population. Conclusions: COVID-19 patients with focal STEMI and diffuse STE elevations are associated with worse survival and clinical outcomes.
Annals Graphic Medicine - Intern Year 2020: Expectations Versus Reality
Authors: Diana Zychowski
Journal: Annals of Internal Medicine (2021)

Web ExclusivesMay 2021Annals Graphic Medicine - Intern Year 2020: Expectations Versus RealityFREEDiana Zychowski, MD, MPHDiana Zychowski, MD, MPHUniversity of Minnesota, Minneapolis, Minnesota (D.Z.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0087 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Minnesota, Minneapolis, Minnesota (D.Z.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0087.Author/Illustrator Information: Diana Zychowski, MD, MPH, is an internal medicine resident and soon-to-be infectious disease fellow (e-mail, diana.[email protected]com).This article was published at Annals.org on 11 May 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGraphic Medicine: Comics as a Patient Education Resource May 2021Volume 174, Issue 5Page: W52-W53 ePublished: 11 May 2021 Issue Published: May 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
p38 MAPK and NF-κB Survival Pathways As Targets for Action of Rituximab In Vivo in a Xenographic Model,
Authors: Gabriel G Vega, Monica Arteaga-Campos, Melisa Martinez-Paniagua, Natividad Neri Munoz, M. J Nambo, Isabel Alvarado, Ivonne Cuadra, Sara Huerta-Yepez, Mario Vega
Journal: Blood (2017)
Abstract 12588: Characteristics and Survival After Transcatheter Aortic Valve Replacement in Immunocompromised Patients: A Cohort Study
Authors: Alexander Ghannam, Colleen Ball, Shahyar Gharacholou, Peter Pollak, Pragnesh Parikh, Carolyn Landolfo, Mays Ali, Kevin Landolfo
Journal: Circulation (2020)

Background: Immunocompromised (IC) patients are at greater risk from cardiac surgery. Transcatheter aortic valve replacement (TAVR) may be more preferable for treating severe aortic stenosis (AS), though data regarding outcomes of IC patients are limited. Methods: We reviewed TAVR procedures performed at our institution from 1/2015-12/2019.We defined IC as either active malignancy receiving oncologic treatment or post organ transplant on immunosuppression, HIV, chronic steroid use (&gt;5mg/day), or autoimmune disorder. Survival probability was estimated using the Kaplan-Meier (KM) method. Cox regression was used to evaluate the association of IC with survival. Results: Of 173 patients who underwent TAVR, 56 (32%) were IC: 30 (54%) had active malignancy undergoing active treatment, 19 (34%) were IC without malignancy, and 7 (13%) had both. Among the 19 IC patients without malignancy, 4 were post organ transplant, 3 were taking chronic steroids, 2 had autoimmune disorder, 1 had HIV, and 10 had ≥2 combination of the above. IC patients, as compared to non-IC patients, had similar baseline demographics and STS risk score (median 4.3 vs. 4.4), respectively. There were 37 deaths (16 IC and 21 non-IC) over a median follow up of 1.4 years (IQR 1.0-2.0 years). 1-year survival after TAVR was 84.5% for IC patients and 89.0% for non-IC patients (log rank p = 0.51). After adjusting for age and sex, an association between IC and survival was observed but not found to be statistically significant (adjusted HR, 1.55; 95% CI, 0.80-3.00). Conclusions: IC patients undergoing TAVR have similar baseline characteristics as non-IC patients with a trend towards worse survival. Longer term follow-up may help clarify the impact of IC status on survival after TAVR.
Abstract P183: Contribution Of Childhood Risk Factors To Sex Differences In Adult Carotid Imt And Plaques: The Childhood Determinants Of Adult Health Study
Authors: Mohammad Shah, Jing Tian, Marie-Jeanne BUSCOT, Hoang T Phan, Costan Magnussen, Brooklyn Fraser, Terence Dwyer, Thomas H Marwick, Alison Venn, Seana L Gall
Journal: Circulation (2021)

Background: Understanding the origins of sex differences in cardiovascular diseases (CVD) may help with prevention. We examined sex differences in carotid artery IMT and plaques in adulthood including the contribution of childhood risk factors. Methods: Boys and girls aged 7-15 years old from the Australian Schools Health and Fitness Survey in 1985 were followed up in the Childhood Determinants of Adult Health study at ages 36-49 years between 2014-19. Sex differences in adult carotid IMT and plaques, identified with 2D ultrasound of left and right carotid arteries, were examined with linear and log binomial regression, respectively. Childhood sociodemographic, psychosocial, health-related behavioural and biomedical risk factors that might contribute to sex differences in carotid IMT/plaques were identified with purposeful model building. Results: Among 1,286 men and women with vascular measurements of carotid IMT (53% women, mean carotid IMT 0.63 mm ± 0.09 standard deviation) women had thinner carotid IMT measurements than men (β coefficients -0.053 95% CI -0.063, -0.043). Adjusting for age standardised waist circumference (WC), waist/hip ratio (WHR), waist/height ratio (WHtR) and systolic blood pressure (SBP) in childhood reduced the sex difference of carotid IMT in adulthood (see Figure), but a significant sex-difference in carotid IMT remained. Women had a 42% lower risk of plaques than men (Relative Risk 0.58 95% CI 0.42, 0.79). School achievement levels, endurance/power fitness and SBP in childhood partially explained the sex difference in the prevalence of plaques at adulthood (see Figure) as the sex difference decreased and became statistically insignificant. Conclusion: Various factors in childhood had contributed to thicker carotid IMT and higher prevalence of carotid plaques in men compared to women. These findings suggest that the origins of adult sex differences in CVD may begin in childhood. There may be benefits of sex-specific primary prevention programs starting in childhood.
Abstract 16810: Myocardial Perfusion Abnormalities, Ejection Fraction, and Coronary Calcium Score Are Not Associated With All-Cause Mortality Among Potential Kidney Transplant Recipients at Emory University Hospital
Authors: Ryan S Cousins, Billy Mullinax, Lehman Godwin, Adam J Mitchell
Journal: Circulation (2020)

Introduction: Screening for coronary artery disease in patients being considered for kidney transplant is common to stratify morbidity and mortality risk, but the optimal strategy, and its impact on outcomes, remains unclear. Here we test the hypothesis that myocardial perfusion imaging (MPI) abnormalities, left ventricular ejection fraction (LVEF), or coronary artery calcium (CAC) score are associated with all-cause mortality in potential kidney transplant recipients at Emory University Hospital (EUH). Methods: In a retrospective chart review, we assessed the relationship between patient demographics, single-photon emission MPI results, and CAC scoring with post-evaluation outcomes at 5 years in consecutive patients referred for pre-transplant stress testing at EUH in 2015. Mann-Whitney U and Chi-Square tests assessed between-group differences in continuous and categorical variables, respectively. Multivariate analysis was performed using logistic regression models. Results: During the study period, 589 patients (mean age 54 years; SEM 0.512, 58% male, 65% African American) underwent MPI and 424 also underwent CAC scoring. Overall, 90 patients (15%) had abnormal MPI (defined as any fixed or reversible defect) and 54 (9%) died during follow up. Age (mean 53.2 years; SEM 0.533 vs. 57.7 years; SEM 1.73, p=0.008), previous coronary artery bypass graft (CABG) (2.06% vs. 7.41%, p=0.017), and myocardial infarction (MI) post-evaluation (4.11% vs. 18.5%, p&lt;0.001) were associated with all-cause mortality. Age (p=0.032) and MI post-evaluation (p&lt;0.001) remained significant in multivariate analysis. MPI abnormalities, LVEF, and CAC score were not associated with all-cause mortality. Conclusions: Age and MI post-evaluation are associated with increased mortality in potential kidney transplant recipients referred for stress testing at EUH. We found no association between MPI abnormalities, LVEF, or CAC score and all-cause mortality.
Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis
Authors: Hongxia Yan, Abdullah Ali, Lionel Blanc, Anupama Narla, Joseph M. Lane, Erjing Gao, Julien Papoin, John Hale, Christopher D. Hillyer, Naomi Taylor, Patrick G. Gallagher, Azra Raza, Sandrina Kinet, Narla Mohandas
Journal: American Journal of Hematology (2021)

Identification of stage-specific erythroid cells is critical for studies of normal and disordered human erythropoiesis. While immunophenotypic strategies have previously been developed to identify cells at each stage of terminal erythroid differentiation, erythroid progenitors are currently defined very broadly. Refined strategies to identify and characterize BFU-E and CFU-E subsets are critically needed. To address this unmet need, a flow cytometry-based technique was developed that combines the established surface markers CD34 and CD36 with CD117, CD71, and CD105. This combination allowed for the separation of erythroid progenitor cells into four discrete populations along a continuum of progressive maturation, with increasing cell size and decreasing nuclear/cytoplasmic ratio, proliferative capacity and stem cell factor responsiveness. This strategy was validated in uncultured, primary erythroid cells isolated from bone marrow of healthy individuals. Functional colony assays of these progenitor populations revealed enrichment of BFU-E only in the earliest population, transitioning to cells yielding BFU-E and CFU-E, then CFU-E only. Utilizing CD34/CD105 and GPA/CD105 profiles, all four progenitor stages and all five stages of terminal erythroid differentiation could be identified. Applying this immunophenotyping strategy to primary bone marrow cells from patients with myelodysplastic syndrome, identified defects in erythroid progenitors and in terminal erythroid differentiation. This novel immunophenotyping technique will be a valuable tool for studies of normal and perturbed human erythropoiesis. It will allow for the discovery of stage-specific molecular and functional insights into normal erythropoiesis as well as for identification and characterization of stage-specific defects in inherited and acquired disorders of erythropoiesis.
Personalized Cancer Vaccine Approach Safe in Early Trial
Authors: Jennifer Abbasi
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Publications 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 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 journal
Immune cell phenotypes associated with disease severity and long-term neutralizing antibody titers after natural dengue virus infection
Authors: Angeline Rouers, Melissa Hui Yen Chng, Bernett Lee, Menaka P. Rajapakse, Kaval Kaur, Ying Xiu Toh, Durgalakshmi Sathiakumar, Thomas Loy, Tun-Linn Thein, Vanessa W.X. Lim, Amit Singhal, Tsin Wen Yeo, Yee-Sin Leo, Kalpit A. Vora, Danilo Casimiro, Bing Lim, Lisa Tucker-Kellogg, Laura Rivino, Evan W. Newell, Katja Fink
Journal: Cell Reports Medicine (2021)

Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here a systematic, longitudinal analysis of B cell, T cell, and antibody responses in the same patients. Antibody responses as well as T and B cell activation differentiate primary from secondary responses. Hospitalization is associated with lower frequencies of activated, terminally differentiated T cells and higher percentages of effector memory CD4 T cells. Patients with more severe disease tend to have higher percentages of plasmablasts. This does not translate into long-term antibody titers, since neutralizing titers after 6 months correlate with percentages of specific memory B cells, but not with acute plasmablast activation. Overall, our unbiased analysis reveals associations between cellular profiles and disease severity, opening opportunities to study immunopathology in dengue disease and the potential predictive value of these parameters.
Abstract MP63: Childhood-onset Obstructive Sleep Apnea Is Associated With Increased Risk Of Adolescent Hypertension
Authors: Julio Fernandez-Mendoza, Fan He, Susan Calhoun, Alexandros Vgontzas, Duanping Liao, Edward O Bixler
Journal: Circulation (2021)

Introduction: Obstructive sleep apnea (OSA) is an established risk factor for hypertension in adults. However, the association of childhood OSA with an increased risk of hypertension has remained elusive. Hypothesis: Childhood-onset OSA is longitudinally associated with hypertension in adolescence. Methods: We tested this hypothesis in a population-based sample of 421 children (5-12 years) from the Penn State Child Cohort who were followed-up 6-13 years later as adolescents (12-23 years). In-lab polysomnography, to ascertain the apnea/hypopnea index (AHI), and seated blood pressure were assessed at baseline and at follow-up. The presence of hypertension at follow-up was defined based on pediatric criteria dependent upon the subject’s age (below and above 13 years). Logistic regression analyses adjusted for sex, race/ethnicity, age, body mass index percentile and systolic blood pressure percentile at baseline. Results: Childhood OSA that persisted in the transition to adolescence was associated with 2.9-fold (95%CI=1.1-7.4) higher odds of adolescent hypertension. In contrast, childhood OSA that remitted in the transition to adolescence was not associated with increased odds of adolescent hypertension (OR=0.9, 95%CI=0.3-2.6). Adolescent-onset OSA was associated with 1.7-fold (95%CI=1.1-2.9) increased odds of adolescent hypertension. Conclusions: Childhood-onset persistent OSA is a risk factor for hypertension in adolescence. Remission of childhood OSA during this transitional period, which previous research has shown to be highly determined by weight loss, does not confer a significant risk of adolescent hypertension. Early life chronic adverse sleep exposures predict cardiovascular risk in adolescence, a critical developmental period.
Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: A systematic review and meta-analysis
Authors: Tien-Wei Hsu, Brendon Stubbs, Chih-Sung Liang, Tien-Yu Chen, Ta-Chuan Yeh, Chih-Chuan Pan, Che-Sheng Chu
Journal: Ageing Research Reviews (2021)
Designing Hydrogels for 3D Cell Culture Using Dynamic Covalent Crosslinking
Authors: Muhammad Rizwan, Alexander E. G. Baker, Molly S. Shoichet
Journal: Advanced Healthcare Materials (2021)

Designing simple biomaterials to replicate the biochemical and mechanical properties of tissues is an ongoing challenge in tissue engineering. For several decades, new biomaterials have been engineered using cytocompatible chemical reactions and spontaneous ligations via click chemistries to generate scaffolds and water swollen polymer networks, known as hydrogels, with tunable properties. However, most of these materials are static in nature, providing only macroscopic tunability of the scaffold mechanics, and do not reflect the dynamic environment of natural extracellular microenvironment. For more complex applications such as organoids or co-culture systems, there remain opportunities to investigate cells that locally remodel and change the physicochemical properties within the matrices. In this review, advanced biomaterials where dynamic covalent chemistry is used to produce stable 3D cell culture models and high-resolution constructs for both in vitro and in vivo applications, are discussed. The implications of dynamic covalent chemistry on viscoelastic properties of in vitro models are summarized, case studies in 3D cell culture are critically analyzed, and opportunities to further improve the performance of biomaterials for 3D tissue engineering are discussed.