tbuckley/cabot-search huggingface dataset:
AB0005 Association of FCGR2A with response to infliximab in rheumatoid arthritis patients
Authors: A. Montes-Martinez, E. Perez-Pampin, J. Narvaez, J.D. Cañete, F. Navarro-Sarabia, V. Moreiras, A. Fernandez-Nebro, M.D.C. Ordoñez, A. Rodriguez de la Serna, B. Magallanes, J.J. Gomez-Reino, A. Gonzalez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Receptors for the Fc fragment of IgG play an important role in homeostasis and function of antibodies. In addition of their functions related with endogenous antibodies, they also bind biologic drugs that include the Fc fragment of IgG. Therefore, functional polymorphisms in the <i>FCGR2A</i>, <i>FCGR2B</i> and <i>FCGR3A</i> genes have been considered candidates to affect the response to these drugs. <h3>Objectives</h3> We aimed to determine the role of functional Fcγr polymorphisms in the response of patients with RA treated with anti-TNF <h3>Methods</h3> The study has included 299 Spanish patients with RA treated with anti-TNF (52.5% infliximab, 30.4% etanercept and 17.1% adalimumab). Disease activity was evaluated basally, and at 3, 6 and 12 months of treatment. Genotypes for H131R (<i>rs1801274</i>) in <i>FCGR2A</i>, F158V (<i>rs396991</i>) in <i>FCGR3A</i> and I231T (<i>rs1050501</i>) in <i>FCGR2B</i> were determined by single base extension. Analyses included linear regression with change in DAS28 (ΔDAS28) and logistic regression comparing responders and non-responders according to the EULAR criteria. An additive genetic model was considered. Covariates included in the analyses were basal DAS28, gender and drug. <h3>Results</h3> Genotype call rate was 97.8% and genotypes were in accordance with HWE. Genotype frequencies were similar to the described in studies with Europeans. In the global analysis of the three drugs, there was a trend to a better response in the homozygous HH patients for the <i>FCGR2A</i> SNP (ΔDAS28 linear regression P=0.07 at 3 months; P=0.08 at 12 months). When the EULAR-defined responders were compared with the non-responders the difference was significant at 12 months (P=0.036). Considering separately the three anti-TNF drugs, association of <i>FCGR2A</i> was significant with response to infliximab, both in the analysis of ΔDAS28 (P=0.034 at 3 months and P=0.0076 at 12 months) and in the logistic regression of responders <i>vs</i> non-responders (P=0.036 at 12 months). There was no association between response to treatment and genotypes of <i>FCGR3A</i> or <i>FCGR2B</i>. <h3>Conclusions</h3> Our results have shown association of the R allele of <i>FCGR2A</i> with a poor response to anti-TNF, which was more marked in patients treated with infliximab. This SNP should be integrated with other biomarkers to develop therapeutic decision making tools. <h3>Disclosure of Interest</h3> None Declared
Trends in Emergency Department Visits and Hospital Admissions in Health Care Systems in 5 States in the First Months of the COVID-19 Pandemic in the US
Authors: Molly M. Jeffery, Gail D’Onofrio, Hyung Paek, Timothy F. Platts-Mills, William E. Soares, Jason A. Hoppe, Nicholas Genes, Bidisha Nath, Edward R. Melnick
Journal: JAMA Internal Medicine (2020)

As coronavirus disease 2019 (COVID-19) spread throughout the US in the early months of 2020, acute care delivery changed to accommodate an influx of patients with a highly contagious infection about which little was known.To examine trends in emergency department (ED) visits and visits that led to hospitalizations covering a 4-month period leading up to and during the COVID-19 outbreak in the US.This retrospective, observational, cross-sectional study of 24 EDs in 5 large health care systems in Colorado (n = 4), Connecticut (n = 5), Massachusetts (n = 5), New York (n = 5), and North Carolina (n = 5) examined daily ED visit and hospital admission rates from January 1 to April 30, 2020, in relation to national and the 5 states' COVID-19 case counts.Time (day) as a continuous variable.Daily counts of ED visits, hospital admissions, and COVID-19 cases.A total of 24 EDs were studied. The annual ED volume before the COVID-19 pandemic ranged from 13 000 to 115 000 visits per year; the decrease in ED visits ranged from 41.5% in Colorado to 63.5% in New York. The weeks with the most rapid rates of decrease in visits were in March 2020, which corresponded with national public health messaging about COVID-19. Hospital admission rates from the ED were stable until new COVID-19 case rates began to increase locally; the largest relative increase in admission rates was 149.0% in New York, followed by 51.7% in Massachusetts, 36.2% in Connecticut, 29.4% in Colorado, and 22.0% in North Carolina.From January through April 2020, as the COVID-19 pandemic intensified in the US, temporal associations were observed with a decrease in ED visits and an increase in hospital admission rates in 5 health care systems in 5 states. These findings suggest that practitioners and public health officials should emphasize the importance of visiting the ED during the COVID-19 pandemic for serious symptoms, illnesses, and injuries that cannot be managed in other settings.
Integrating Personalized Medicine With Population Health Management
Authors: David C. Grossman, Eric B. Larson, Harold C. Sox
Journal: JAMA (2020)

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
Exhaled breath analysis by use of eNose technology: a novel diagnostic tool for interstitial lung disease
Authors: Catharina C. Moor, Judith C. Oppenheimer, Gizal Nakshbandi, Joachim G.J.V. Aerts, Paul Brinkman, Anke-Hilse Maitland-van der Zee, Marlies S. Wijsenbeek
Journal: European Respiratory Journal (2020)

Early and accurate diagnosis of interstitial lung diseases (ILDs) remains a major challenge. Better noninvasive diagnostic tools are much needed. We aimed to assess the accuracy of exhaled breath analysis using eNose technology to discriminate between ILD patients and healthy controls, and to distinguish ILD subgroups.In this cross-sectional study, exhaled breath of consecutive ILD patients and healthy controls was analysed using eNose technology (SpiroNose). Statistical analyses were done using partial least square discriminant analysis and receiver operating characteristic analysis. Independent training and validation sets (2:1) were used in larger subgroups.A total of 322 ILD patients and 48 healthy controls were included: sarcoidosis (n=141), idiopathic pulmonary fibrosis (IPF) (n=85), connective tissue disease-associated ILD (n=33), chronic hypersensitivity pneumonitis (n=25), idiopathic nonspecific interstitial pneumonia (n=10), interstitial pneumonia with autoimmune features (n=11) and other ILDs (n=17). eNose sensors discriminated between ILD and healthy controls, with an area under the curve (AUC) of 1.00 in the training and validation sets. Comparison of patients with IPF and patients with other ILDs yielded an AUC of 0.91 (95% CI 0.85-0.96) in the training set and an AUC of 0.87 (95% CI 0.77-0.96) in the validation set. The eNose reliably distinguished between individual diseases, with AUC values ranging from 0.85 to 0.99.eNose technology can completely distinguish ILD patients from healthy controls and can accurately discriminate between different ILD subgroups. Hence, exhaled breath analysis using eNose technology could be a novel biomarker in ILD, enabling timely diagnosis in the future.
Abstract 15242: Non-Diagnostic Dobutamine Stress Echocardiogram by Failing to Achieve Target Heart Rate Predicts Long Term All Cause Mortality
Authors: Divyang Patel, Anirudh Kumar, Paul Cremer, Serge C Harb, Sneha Vakamudi, Zoran B Popovic, L Leonardo L Rodriguez, Richard A Grimm, Milind Desai, Brian P Griffin, Samir R kapadia, Venu Menon, Wael A Jaber, Vidyasagar Kalahasti
Journal: Circulation (2019)

Introduction: Dobutamine stress echocardiography (DSE) is used as a noninvasive test to risk stratify patients with coronary artery and valvular heart disease. While many studies have examined vari...
Omalizumab for the treatment of chronic inducible urticaria in 80 patients
Authors: V. Exposito‐Serrano, L. Curto‐Barredo, P. Aguilera Peiro, S. Gómez Armayones, E. Serra‐Baldrich, J. Spertino, M. Bonfill Ortí, I. Figueras Nart, G. Melé‐Ninot, C. Baliu‐Piqué, A. Sala Cunill, M. Labrador‐Horrillo, A. Guilabert Vidal, N. Fernández Chico, A.M. Giménez‐Arnau
Journal: British Journal of Dermatology (2020)
LIM-Nebulette Reinforces Podocyte Structural Integrity by Linking Actin and Vimentin Filaments
Authors: Xuhua Ge, Tao Zhang, Xiaoxia Yu, Alecia N. Muwonge, Nanditha Anandakrishnan, Nicholas J. Wong, Jonathan C. Haydak, Jordan M. Reid, Jia Fu, Jenny S. Wong, Smiti Bhattacharya, Christina M. Cuttitta, Fang Zhong, Ronald E. Gordon, Fadi Salem, William Janssen, James C. Hone, Aihua Zhang, Hong Li, John C. He, G. Luca Gusella, Kirk N. Campbell, Evren U. Azeloglu
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement The functional basis of the spatial cytoskeletal organization in the kidney podocyte that gives rise to its unique interdigitating morphology has been elusive. An integrative approach identified a novel podocyte-specific actin-associated protein, LIM-nebulette, that brings vimentin intermediate filaments to actin microfilaments, promoting mechanical stability, by regulating focal adhesions, calcium dynamics, and Rho GTPase activity. Silencing of LIM-nebulette is associated with aberrant biophysical properties in human podocytes in culture as well as with multiple glomerulopathies in patients, at both the RNA transcript and protein levels. Background Maintenance of the intricate interdigitating morphology of podocytes is crucial for glomerular filtration. One of the key aspects of specialized podocyte morphology is the segregation and organization of distinct cytoskeletal filaments into different subcellular components, for which the exact mechanisms remain poorly understood. Methods Cells from rats, mice, and humans were used to describe the cytoskeletal configuration underlying podocyte structure. Screening the time-dependent proteomic changes in the rat puromycin aminonucleoside–induced nephropathy model correlated the actin-binding protein LIM-nebulette strongly with glomerular function. Single-cell RNA sequencing and immunogold labeling were used to determine Nebl expression specificity in podocytes. Automated high-content imaging, super-resolution microscopy, atomic force microscopy (AFM), live-cell imaging of calcium, and measurement of motility and adhesion dynamics characterized the physiologic role of LIM-nebulette in podocytes. Results Nebl knockout mice have increased susceptibility to adriamycin-induced nephropathy and display morphologic, cytoskeletal, and focal adhesion abnormalities with altered calcium dynamics, motility, and Rho GTPase activity. LIM-nebulette expression is decreased in diabetic nephropathy and FSGS patients at both the transcript and protein level. In mice, rats, and humans, LIM-nebulette expression is localized to primary, secondary, and tertiary processes of podocytes, where it colocalizes with focal adhesions as well as with vimentin fibers. LIM-nebulette shRNA knockdown in immortalized human podocytes leads to dysregulation of vimentin filament organization and reduced cellular elasticity as measured by AFM indentation. Conclusions LIM-nebulette is a multifunctional cytoskeletal protein that is critical in the maintenance of podocyte structural integrity through active reorganization of focal adhesions, the actin cytoskeleton, and intermediate filaments.
Abstract 210: Effects of Indication for Veno-Arterial Extracorporeal Membrane Oxygenation on Predictive Value of Save Score
Authors: Marinos Kosmopoulos, Jason A Bartos, Demetris Yannopoulos
Journal: Circulation (2019)

Introduction: Veno-Arterial Extracorporeal Membrane Oxygenation (VA ECMO) has emerged as a prominent tool for management of patients with Inability to Wean Off Cardiopulmonary Bypass (IWOCB), extracorporeal cardiopulmonary resuscitation (eCPR) or refractory cardiogenic shock (RCS). The high mortality that is still associated with these diseases urges for the development of reliable prediction models for mortality after cannulation. Survival After VA ECMO (SAVE) Score consists one of the most widely used prediction tools and the only model with external validation. However, its predictive value is still under debate. Hypothesis: Whether VA ECMO indication affects the predictive value of SAVE Score. Methods: 317 patients treated with VA ECMO in a quaternary center (n= 52 for IWOCB, n=179 for eCPR and n=86 for RCS) were retrospectively assessed for differences in SAVE Score and their primary outcomes. The Receiver Operating Characteristic (ROC) curve for SAVE Score and mortality was calculated separately for each VA ECMO indication. Results: The three groups had significant differences in SAVE Score (p&lt;0.01) without significant differences in mortality (p=0.176). ROC Curve calculation indicated significant differences in predictive value of SAVE Score for survival among its different indications. (Area Under the Curve= 81.69% for IWOCB, 53.79% for eCPR and 69.46% for RCS). Conclusion: VA ECMO indication markedly affects the predictive value of SAVE Score. Prediction of primary outcome in IWOCB patients was reliable. On the contrary, routine application for survival estimation in eCPR patients is not supported from our results.
Targeting p53 for the treatment of cancer
Authors: Michael J. Duffy, Naoise C. Synnott, Shane O’Grady, John Crown
Journal: Seminars in Cancer Biology (2020)

Dysfunction of the TP53 (p53) gene occurs in most if not all human malignancies. Two principal mechanisms are responsible for this dysfunction; mutation and downregulation of wild-type p53 mediated by MDM2/MDM4. Because of its almost universal inactivation in malignancy, p53 is a highly attractive target for the development of new anticancer drugs. Although multiple strategies have been investigated for targeting dysfunctional p53 for cancer treatment, only 2 of these have so far yielded compounds for testing in clinical trials. These strategies include the identification of compounds for reactivating the mutant form of p53 back to its wild-type form and compounds for inhibiting the interaction between wild-type p53 and MDM2/MDM4. Currently, multiple p53-MDM2/MDM4 antagonists are undergoing clinical trials, the most advanced being idasanutlin which is currently undergoing testing in a phase III clinical trial in patients with relapsed or refractory acute myeloid leukemia. Two mutant p53-reactivating compounds have progressed to clinical trials, i.e., APR-246 and COTI-2. Although promising data has emerged from the testing of both MDM2/MDM4 inhibitors and mutant p53 reactivating compounds in preclinical models, it is still unclear if these agents have clinical efficacy. However, should any of the compounds currently being evaluated in clinical trials be shown to have efficacy, it is likely to usher in a new era in cancer treatment, especially as p53 dysfunction is so prevalent in human cancers.
Intramyocardial Injection of Bone Marrow Mononuclear Cells in Patients with Chronic Myocardial Ischemia: an Intra-Patient Comparison
Authors: S. Rodrigo, J. van Ramshorst, S.L. Beeres, P. Dibbets-Schneider, A. de Roos, W.E. Fibbe, J.J. Zwaginga, E.E. van der Wall, M.J. Schalij, J.J. Bax, D.E. Atsma
Journal: Circulation (2011)
Lessons of COVID-19: A roadmap for post-pandemic science
Authors: Tanya S. Freedman, Mark B. Headley, Nina Serwas, Megan Ruhland, Carlos A. Castellanos, Alexis J. Combes, Matthew F. Krummel
Journal: The Journal of Experimental Medicine (2020)

The response to the COVID-19 crisis across most research institutions mandated ceasing nonessential research activities in order to minimize the spread of the virus in our communities. With minimal notice, experiments were terminated, cell lines were frozen, mouse colonies were culled, and trainees were prevented from performing bench research. Still, despite the interruption of experimental productivity, the shutdown has proven for many PIs and trainees that doing and thinking science are not activities that are bound to the laboratory. Furthermore, the shutdowns have solidified important emerging trends and forced us to further innovate to get the most out of working remotely. We hope that some of these innovations, hard-gained in this difficult time, will persist and develop into new paradigms—lessons that will improve our science and our relationship to the climate and community beyond the current pandemic.
Stimuli-responsive In situ gelling system for nose-to-brain drug delivery
Authors: Mukta Agrawal, Shailendra Saraf, Swarnlata Saraf, Sunil K. Dubey, Anu Puri, Umesh Gupta, Prashant Kesharwani, V. Ravichandiran, Pramod Kumar, V.G.M. Naidu, Upadhyayula Suryanarayana Murty, None Ajazuddin, Amit Alexander
Journal: Journal of Controlled Release (2020)
Cyclosporine: an old weapon in the fight against coronaviruses
Authors: Adam Molyvdas, Sadis Matalon
Journal: European Respiratory Journal (2020)

Coronaviruses have been known to cause respiratory infections in humans and intestinal infections in other mammals. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is the seventh virus of the Coronaviridae family that is known to infect humans. Until 2002, four Coronaviruses infecting humans were described (HCoV-NL63, HCoV-229E, HCoV-OC43 and HKU1). These viruses caused only mild respiratory diseases in immunocompetent hosts. Since 2002, three highly pathogenic viruses from this family have been identified. SARS-CoV (also referred to as SARS-CoV-1) is an enveloped, positive-sense, single-stranded RNA virus which infects the epithelial cells within the lungs. The virus enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2) [1]. It infects humans, bats and palm civets [1]. Cyclosporine inhibits the replication of coronaviruses and could potentially suppress the cytokine storm associated with coronavirus infections <https://bit.ly/39x2PSt>
Comment on ‘Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab’
Authors: Attila Pethoe-Schramm, Jenny Devenport, William Reiss
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the article ‘Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab’ by Shafran et al .1 This was an exploratory analysis of multiple studies and concluded that baseline C-reactive protein (CRP) and its early course may inform, to some extent, the estimation of potential therapeutic success in patients with rheumatoid arthritis (RA) treated with tocilizumab. Although we appreciate the pursuit of personalised treatment decisions in RA, this conclusion is not the only interpretation, and previously published analyses of these data further characterise the relationship between CRP and clinical outcomes with tocilizumab treatment in patients with RA.2

Shafran et al 1 concluded that baseline and early changes in CRP levels are predictive of tocilizumab response. Although CRP levels were affected differently by tocilizumab than rituximab or methotrexate treatment, decreasing to near zero in tocilizumab-treated patients, the …
Sub-cellular compartmentalization of Jak2 as a unique mechanism for the inhibition of Jak2-Stat3 signaling
Authors: Vaibhav Kapuria, Geoffrey Bartholomeusz, Ling Y Kong, William G Bornmann, Nicholas J Donato
Journal: Cancer Research (2007)

2390  Janus kinase 2 (JAK2) is a cytokine receptor associated tyrosine kinase. Binding of cytokines to their specific receptors leads to their dimerization and activation of associated JAKs. Activated JAKs phosphorylate specific tyrosine residues in the cytoplasmic chains of the receptor, which now act as docking sites for SH2 containing latent transcription factors known as STATs. Once bound to the receptor, STATs are activated by JAKs through phosphorylation of their tyrosine residues. Activated STATs form stable dimers and translocate to the nucleus, where they bind specific promoter sequences of their target genes involved in cell proliferation and survival, such as Bcl-xL, Bcl-2, c-myc and cyclin D1. Tumor cell lines and samples derived from hematopoetic malignancies (leukemia, lymphoma and multiple myeloma) and solid tumors (breast, head and neck, lung, prostrate and ovarian cancers) exhibit deregulated JAK-STAT signaling, which can be attributed to autocrine cytokine production or growth factor stimulation by tumor cells or microenvironment. Tel-JAK2 mutants, caused by chromosomal translocations, are constitutively active and induce myeloid and lymphoid leukemias. Recent studies have also demonstrated an activating mutation in JAK2 (V617F) which underlies many myeloid disorders. Tryphostin AG490 is the most commonly studied kinase inhibitor of JAK2. Although AG490 inhibits tumor cell growth and increases sensitivity to apoptotic stimuli in vitro, in vivo studies have been less promising as AG490 has limited activity in animals and high concentrations (50-100 μM) are required to achieve significant anti-tumor effects. In a search for more effective inhibitors of JAK2, our research group screened over 300 analogs of AG490 for their ability to inhibit JAK2. Based in structure activity analysis, a small molecule inhibitor was designed and synthesized (WP1130), which inhibited JAK2 mediated STAT3 activation by inducing down regulation of JAK2 at low μM concentrations. JAK2 down-regulation by WP1130 was a rapid process which could not inhibited by proteasomal, lysosomal, or other serine/threonine protease inhibitors. Recent results show that WP1130 treatment causes translocation of JAK2 from the soluble cytoplasmic fraction into the detergent insoluble fraction. Altered partitioning of JAK2, not direct kinase inhibition, appears to be responsible for the suppression of downstream signaling. Compartmentalization of JAK2 by WP1130 has been seen in most cell lines examined and is distinct from other commercially available JAK2 inhibitors. In vivo studies also show WP1130 has significant anti-tumor effects as compared to parental AG490 compound. Other kinases such as HER2, Btk, Src etc are not effected by WP1130, demonstrating its target specificity. The unique mechanism of WP1130 may be exploited for therapy in many forms of cancers and malignancies where JAK2 plays pivotal role.