tbuckley/cabot-search huggingface dataset:
Abstract 021: C-reactive Protein Partially Mediates The Inverse Association Between Coffee Consumption And Risk Of Type 2 Diabetes: Findings From The UK Biobank And The Rotterdam Studies
Authors: Carolina Ochoa-Rosales, Niels van der Schaft, Kim V Braun, Frederick Ho, Fanny Petermann, Jill Pell, Mohammad A Ikram, Carlos Celis-Morales, Trudy Voortman
Journal: Circulation (2021)

Background: Coffee intake has been linked to lower type 2 diabetes (T2D) risk. We hypothesized this may be mediated by coffee’s effects on inflammation. Methods: Using participants from the UK Biobank (UKB n=145370) and Rotterdam Study (RS n=7172) cohorts, we studied associations of coffee intake with incident T2D; longitudinally measured insulin resistance (HOMA IR); serum levels of inflammation markers; and the mediating role of inflammation. Statistical regression models were adjusted for sociodemographic, lifestyle and health factors. Results: The median follow up was 7 (UKB) and 9 (RS) years. An increase of one coffee cup/day was associated with 4-6% lower T2D risk (RS HR=0.94 [95% CI 0.90; 0.98]; UKB HR=0.96 [0.94; 0.98]); lower HOMA IR (RS β=-0.017 [-0.024; -0.010]); with lower C reactive protein (CRP) and higher adiponectin (Figure1). Consumers of filtered coffee had the lowest T2D risk (UKB HR=0.88 [0.83; 0.93]). CRP levels mediated 9.6% (UKB) and 3.4% (RS) of the total effect of coffee on T2D (Figure 1). Conclusions: We suggest that coffee’s beneficial effects on lower T2D risk are partially mediated by improvements in systemic inflammation.Figure 1. a CRP and a adiponectin refer to the effect of coffee intake on CRP and adiponectin levels. a CRP RS : β=-0.014 (-0.022; -0.005); UKBB a CRP UKB : β=-0.011 (-0.012; -0.009) and RS a adiponectin : β=0.025 (0.007; 0.042). b CRP and b adiponectin refer to the effect of coffee related levels in CRP and adiponectin on incident T2D, independent of coffee. RS b CRP : HR=1.17 (1.04; 1.31); UKB b CRP : HR=1.45 (1.37; 1.54); and b adiponectin : HR=0.58 (0.32; 0.83). c′ refers to coffee’ effect on T2D going directly or via others mediators. UKB c′ independent of CRP : HR=0.96 (0.94; 0.99); RS c′ independent of CRP : HR=0.94 (0.90; 0.99); and RS c′ independent of CRP+adiponectin : HR=0.90 (0.80; 1.01). Coffee related changes in CRP may partially explain the beneficial link between coffee and T2D, mediating a 3.4% (0.6; 4.8, RS) and 9.6% (5.7; 24.4, UKB). Evidence of mediation was also found for adiponectin.
Abstract 16548: Low-dose Amiodarone for Control of Atrial Fibrillation (AF) Remains Effective in Patients With Ejection Fraction Less Than 50%
Authors: Frank A McGrew, Sandy Charlton, Brian Dragutsky
Journal: Circulation (2020)

Introduction: Our previous work has shown low-dose Amiodarone (often less than 600 mg per week) is effective for control of AF in a forced down-titration schema. Many studies have shown restoration of sinus rhythm in patients with CHF shows promise for reduced mortality and morbidity. This analysis compares results of this protocol in patients with ejection fraction above and below 50%. Methods: Consecutive patients with atrial fibrillation deemed suitable for Amiodarone therapy were prospectively followed with a forced down-titration protocol. Controlled atrial fibrillation was defined as an AF burden of less than 1% on device diagnostics (30% of patients) or no symptoms and sinus rhythm on clinical visit EKGs. Demographic and clinical data were analyzed for patients with ejection fraction above and below 50%. Results: Patients with EF less than 50% had greater success (35/38) or 92% than patients with ejection fraction greater than 50% (39/51) or 76%. However, patients with ejection fraction under 50% required larger doses. See graph for detailed doses. Overall success was good in both groups with no sustained side effects. Conclusions: Amiodarone in low doses is effective in control of atrial fibrillation in patients across the spectrum of ejection fractions. Lower ejection fractions may require a somewhat higher dose (less than 1000 mg per week) but at a higher success rate.Larger studies could potentially show the impact of this protocol on mortality.
Alzheimer mutant speeds APP transport
Authors: Sam Gandy, Michelle E. Ehrlich
Journal: The Journal of Experimental Medicine (2021)

APPS198P segregates with rare familial forms of Alzheimer’s disease and resides within exon 5, unlike 27 other mutations that reside in exons 16 or 17. In this issue, Zhang et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210313) show that the brains of APPS198P transgenic mice accumulate excess levels of Aβ. In cultured cells, APPS198P undergoes accelerated ER folding, leading to early arrival in late vesicular compartments, thereby enhancing generation of Aβ.
Evaluation of Predictors for Radiation Exposure Dose and Radiation Damage during Elective Percutaneous Coronary Intervention
Authors: Nakashima Emiko, Hikita Hiroyuki, Kuroda Syunsuke, Nagai Nao, Kawaguchi Naohiko, Fujinami Tatsuya, Kusa Shigeki, Kamiishi Tetsuo, Ohkubo Kenji, Fujino Tadashi, Takahashi Yoshihide, Nozato Toshihiro, Kuwahara Taishi, Isobe Mitsuaki, Takahashi Atsushi
Journal: Circulation (2011)
Abstract 13636: Sulfated Inositol-Based Glycosaminoglycan Mimetics are Homogeneous, Potent, Selective, and Allosteric Inhibitors of Factor XIa
Authors: Rami A Al-Horani, Umesh R Desai
Journal: Circulation (2017)

Thrombin and factor Xa-dependent anticoagulants do not distinguish between thrombin generation contributing to thrombosis from that required for hemostasis, and therefore, all are associated with a...
Highly specific monoclonal antibodies and epitope identification against SARS-CoV-2 nucleocapsid protein for antigen detection tests
Authors: Yutaro Yamaoka, Kei Miyakawa, Sundararaj Stanleyraj Jeremiah, Rikako Funabashi, Koji Okudela, Sayaka Kikuchi, Junichi Katada, Atsuhiko Wada, Toshiki Takei, Mayuko Nishi, Kohei Shimizu, Hiroki Ozawa, Shuzo Usuku, Chiharu Kawakami, Nobuko Tanaka, Takeshi Morita, Hiroyuki Hayashi, Hideaki Mitsui, Keita Suzuki, Daisuke Aizawa, Yukihiro Yoshimura, Tomoyuki Miyazaki, Etsuko Yamazaki, Tadaki Suzuki, Hirokazu Kimura, Hideaki Shimizu, Nobuhiko Okabe, Hideki Hasegawa, Akihide Ryo
Journal: Cell Reports Medicine (2021)

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a major global public health concern. Although rapid point-of-care testing for detecting viral antigen is important for management of the outbreak, the current antigen tests are less sensitive than nucleic acid testing. In our current study, we produce monoclonal antibodies (mAbs) that exclusively react with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and exhibit no cross-reactivity with other human coronaviruses, including SARS-CoV. Molecular modeling suggests that the mAbs bind to epitopes present on the exterior surface of the nucleocapsid, making them suitable for detecting SARS-CoV-2 in clinical samples. We further select the optimal pair of anti-SARS-CoV-2 nucleocapsid protein (NP) mAbs using ELISA and then use this mAb pair to develop immunochromatographic assay augmented with silver amplification technology. Our mAbs recognize the variants of concern (501Y.V1-V3) that are currently in circulation. Because of their high performance, the mAbs of this study can serve as good candidates for developing antigen detection kits for COVID-19.
Relative Lymphocytosis Is Associated with Improved Outcome in Myelofibrosis and May Account for the Favorable Prognosis of the Calr mutation
Authors: Andrew Kuykendall, Chetasi Talati, Pearlie Epling-Burnette, Najla Al Ali, Eric Padron, Kendra L. Sweet, David A Sallman, Jeffrey E. Lancet, Alan F. List, Kenneth S. Zuckerman, Rami S. Komrokji
Journal: Blood (2017)
2 NOVEL MUTATIONS IN RED-CELL BAND-4.2 DEFICIENCY - HOMOZYGOUS 175-GAT-]TAT, AND COMPOUND HETEROZYGOUS 142-GCT-]ACT WITH 317-CGC-]TGC
Authors: Yawata Y, Kanzaki A, Okamoto N, Inoue T, Yawata A, Harano T, Harano K, Yasunaga M
Journal: Blood (1994)
Racial and Ethnic Diversity Among Obstetrics and Gynecology, Surgical, and Nonsurgical Residents in the US From 2014 to 2019
Authors: Claudia L. López, Machelle D. Wilson, Melody Y. Hou, Melissa J. Chen
Journal: JAMA Network Open (2021)

Davis, institutional review board determined that this cross-sectional study was not human participants research; therefore, it
Prognostic Implications of Associated Cardiac Abnormalities Detected on Echocardiography in Patients With Moderate Aortic Stenosis
Authors: Mohammed Rizwan Amanullah, Stephan Milhorini Pio, Arnold C.T. Ng, Kenny Y.K. Sin, Nina Ajmone Marsan, Zee Pin Ding, Martin B. Leon, Philippe Généreux, Victoria Delgado, See Hooi Ewe, Jeroen J. Bax
Journal: JACC. Cardiovascular imaging (2021)
Abstract 17049: Outcomes of Bioprosthetic and Mechanical Aortic Valve Replacement in Patients With Congenital Heart Disease
Authors: Reilly D Hobbs, Megan Schultz, Catherine Wagner, Richard G Ohye, Edward Bove, Ming-Sing Si
Journal: Circulation (2020)

Introduction: Aortic valve replacement (AVR) is required in patients with congenital heart disease who are not candidates for Ross procedure or valve repair. The long-term outcomes of prosthetic AVR in patients with congenital heart disease are unknown. Methods: A single-institution, retrospective review of all patients treated with mechanical (M) and bioprosthetic (BP) AVR between 12/1985 to 2/2020 was undertaken. Results: One-hundred and ninety-three patients underwent BP (n=134) or M (n=59) AVR. Indications for AVR were insufficiency (91/193), stenosis (61/194), mixed (38/193), aneurysm (2/193), and unknown (1/193). Patients receiving M valves were more likely to be younger (18.5 years versus 29.0 years, p &lt; 0.01) and less likely to require subsequent valve reintervention (p &lt; 0.01). Average time to first reintervention was 76 and 71 months in the BP and M groups respectively (p = 0.785). Survival between the M and BP groups was similar (p = 0.120). Twenty-four patients who received a M valve and thirteen patients who received a BP valve died during the study period. Causes of death were cardiac (16/37), stroke (3/37), non-cardiac (4/37), and unknown (14/37). Conclusions: Long-term freedom from death or valve reintervention is poor in congenital heart disease patients requiring AVR. Survival is similar between patients treated with M and BP valves, however, BP valves more frequently required reintervention during the study period. Both BP and M valves are associated with significant long-term mortality. These results highlight the need for the development of robust aortic valve repair techniques so that AVR can be avoided.
Abstract 12604: Effect of Psychotherapy on Quality of Life and Recurrence of Events in Patients With Recurrent Vasovagal Syncope: A Randomized Study
Authors: Renata de Barros e Silva, Denise Hachul, PEDRO GABRIEL M DE BARROS E SILVA, Mauricio I Scanavacca
Journal: Circulation (2020)

Introduction: Vasovagal syncope presents a benign prognosis in terms of survival but is associated with significant impairment on quality of life (QoL). Poor emotional status contributes to the recurrence of events. Hypothesis: Among patients with recurrent vasovagal syncope, weekly sessions of psychotherapy may improve QoL and reduce the number of events during one year of follow-up. Methods: A randomized controlled trial was conducted including 10 patients with recurrent vasovagal syncope and positive tilt test. Cardiac disease and ongoing psychotherapeutic interventions were the main exclusion criteria. After randomization, half of the eligible patients underwent weekly sessions of psychotherapy during 12 months, while the control group was followed according to the standard of care, without psychotherapy. QoL by SF-36 and recurrence of syncope and pre-syncope were compared between the 2 groups and also in each group pre and post randomization. Results: All patients had a positive tilt test (80% with mixed vasovagal response), 70% were female and the mean age was 47.4 ± 11.1 years. The average rate of events before inclusion was 4.1 (± 3.4) syncopes/year and 1.26 (± 0.5) episodes of presyncope/week. The groups were well balanced at baseline and all patients completed the planned follow-up of one year. In the assessment of QoL by SF-36, comparing before and one year after randomization, there was no statistically significant difference in the control group (49.9 ± 9.8 vs 46.9 ± 3.4, P = 0.20) but there was a significant improvement in the intervention group (44.9 ± 11.9 vs 68.8 ± 7.8, P &lt; 0.01). Comparing both groups at 12 months, patients that underwent sessions of psychotherapy had better QoL (68.8 ± 7.8 vs 46.9 ± 3.4, P &lt; 0.01). Regarding the recurrence of syncope events, there was no significant change in the control group; however, in the intervention group there was a significant reduction in the rate of presyncope episodes per month (5.6 ± 2.1 vs 1.7 ± 0.9; P = 0.02) and also a significant reduction in the rate of syncope per year (4.6 ± 3.3 vs 1.0 ± 0.7; P = 0.04). Conclusions: In a randomized clinical trial, patients with recurrent vasovagal syncope undergoing regular psychotherapeutic intervention had less recurrence of events and improved quality of life in one year.
Abstract 15608: Atp Citrate Lyase a New Signaling Hub Between Metabolism and Epigenetic in Vascular Remodeling and Right Ventricle Failure in Pulmonary Arterial Hypertension
Authors: Charlotte romanet, Alice Bourgeois, Yann Grobs, Sandra Breuils Bonnet, Valerie Nadeau, Steeve Provencher, Olivier BOUCHERAT, Sebastien Bonnet
Journal: Circulation (2020)

Objective: Pulmonary arterial hypertension (PAH) is a lung disease characterized by vascular lesions and obstruction of distal pulmonary arteries (PA) leading to right ventricle (RV) remodeling and death. Similar to cancer cells, PA smooth muscle cells (PASMCs) exhibit an excessive proliferation and resistance to apoptosis, pivot components of vascular remodeling, due to epigenetic reprogramming and Warburg effect. This epigenetic/metabolic signature is attributed in part to the upregulation of ATP citrate lyase (ACLY). By decreasing cytosolic levels of citrate, ACLY supports glycolysis, while by generating acetyl-coA in the nucleus it promotes histone acetylation and signaling pathways supporting pathological processes like proliferation, hypertrophy, and fibrosis, pathological features in PAH. In the cytosol, ACLY controls the synthesis of lipids required for proliferating cells to generate membranes. We thus hypothesized that ACLY is upregulated in PAH and contributes to PA remodeling and RV failure. Methods/Results: Using immunoblot, we showed an upregulation of ACLY in human distal PA and isolated PASMCs from PAH patients (p&lt;0.05 ; n=10), like in Sugen/Hypoxia rat model. In vitro, pharmacological inhibition of ACLY significantly decreased PAH-PASMC proliferation (Ki67 labeling), resistance to apoptosis (Annexin V and caspase 3 assays) and restored a proper metabolism (seahorse assay) (p&lt;0.05 ; n=5). Mechanistically, we showed that ACLY inhibition decreases P300-dependent pro-survival factors including Survivin, PCNA, cMYC, PKM2, phospho-PDH / PDH, and restores FOXO3 and AMPK functions know to be decreased in PAH. Besides, we found that ACLY expression was upregulated in failed RV from rats subjected to pulmonary artery banding; its expression correlating negatively with stroke volume and positively with RVEDP; hypertrophy and fibrosis. Conclusion: Our preliminary data suggest that ACLY contributes to vascular remodeling in PAH. Current experiments aim to demonstrate whether 1) pharmacological inhibition of ACLY reverses PAH in animal models and 2) whether inactivation of Acly targeted to smooth muscle cells and cardiomyocytes improves pulmonary vascular remodeling and RV dysfunction, respectively.
Removing Race From Kidney Function Estimates
Authors: Anna C. van der Burgh, Ewout J. Hoorn, Layal Chaker
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
Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia
Authors: Marie-Emilie Dourthe, Florence Rabian, Karima Yakouben, Florian Chevillon, Aurélie Cabannes-Hamy, Françoise Méchinaud, Audrey Grain, Delphine Chaillou, Ilhem Rahal, Sophie Caillat-Zucman, Emmanuelle Lesprit, Jérôme Naudin, Julie Roupret-Serzec, Nathalie Parquet, Anne Brignier, Valérie Guérin-El Khourouj, Elodie Lainey, Aurélie Caye-Eude, Hélène Cavé, Emmanuelle Clappier, Stéphanie Mathis, Elie Azoulay, Jean Hugues Dalle, Nathalie Dhédin, Isabelle Madelaine, Jérôme Larghero, Nicolas Boissel, André Baruchel
Journal: Leukemia (2021)
Deconvolution of cell type-specific drug responses in human tumor tissue with single-cell RNA-seq
Authors: Wenting Zhao, Athanassios Dovas, Eleonora Francesca Spinazzi, Hanna Mendes Levitin, Matei Alexandru Banu, Pavan Upadhyayula, Tejaswi Sudhakar, Tamara Marie, Marc L. Otten, Michael B. Sisti, Jeffrey N. Bruce, Peter Canoll, Peter A. Sims
Journal: Genome Medicine (2021)

Abstract Background Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Methods We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses. Results We used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment. Conclusions Acute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.
US Childhood Asthma Incidence Rate Patterns From the ECHO Consortium to Identify High-risk Groups for Primary Prevention
Authors: Christine Cole Johnson, Aruna Chandran, Suzanne Havstad, Xiuhong Li, Cynthia T. McEvoy, Dennis R. Ownby, Augusto A. Litonjua, Margaret R. Karagas, Carlos A. Camargo, James E. Gern, Frank Gilliland, Alkis Togias, Cristiane Duarte, Daniel J. Jackson, Irva Hertz-Picciotto, Catherine Karr, Leslie Leve, Emily Oken, Nigel Paneth, Frederica P. Perera, Rosalind J. Wright, John Vena, Dana Dabelea, Fernando Martinez, Tina V. Hartert, Diane R. Gold, Gurjit K. Khurana-Hershey, Anne Wright
Journal: JAMA Pediatrics (2021)

Asthma is the leading chronic illness in US children, but most descriptive epidemiological data are focused on prevalence.
Abstract 16549: Trimethylamine N-Oxide-Derived Endothelial Microvesicles Induce a Dysfunctional Endothelial Cell Phenotype
Authors: Vinicius Garcia, L. Madden Brewster, Kelly A Stockelman, Hannah K Fandl, Clay Rahaman, Lukas Maly, Jared J Greiner, Kevin P Davy, Christopher Desouza
Journal: Circulation (2020)

Introduction: Gut microbiota-generated increases in trimethylamine N-oxide (TMAO) has been linked to atherosclerosis and major adverse cardiovascular events. Experimental and clinical studies suggest that TMAO impairs endothelial cell function resulting in a proatherogenic endothelial phenotype. Endothelial microvesicles (EMVs) are anucleate vesicles shed constitutively by the endothelium aiding in cell-to-cell communication, activate repair or defense mechanisms, and/or stimulate immune responses. Under pathologic conditions, however, EMVs are released in greater number and their functional phenotype is more likely to evoke dysfunctional cellular effects. The experimental aims of this study were to determine: 1) if TMAO stimulates EMV release from endothelial cells in vitro ; and 2) the effects of TMAO-generated EMVs on endothelial cell inflammation, apoptosis, autophagy and nitric oxide (NO) production. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with TMAO (100 μmol) for 24 h. EMVs released into the supernatant from cells treated with TMAO or vehicle were isolated and quantified by flow cytometry. Fresh HUVECs were treated with either TMAO-derived or control EMVs for 24 h. Results: EMV release was significantly higher in cells treated with TMAO compared with control (55±3 vs 28±3 EMV/μL). TMAO-generated EMVs induced significantly higher release of interleukin (IL)-6 (33.9±2.6 vs 20.2±1.3 pg/mL) and IL-8 (45.4±2.6 vs 33.1±1.6 pg/mL) and active NF-κB p65 (Ser536) (17.4±1.3 vs 7.7±1.0 AU) expression than control EMVs. TMAO EMVs significantly increased cell expression of apoptotic proteins caspase-9 (198.5±19.4 vs 119.7±11.2 AU) and active caspase-3 (17.7±2.8 vs 11.3±0.7 AU) and markedly depressed eNOS activity (10.6±0.9 vs 6.9±0.6 AU) and NO production (7.7±0.4 vs 5.5±0.6 μmol/L). In addition, cell autophagy was dysregulated by TMAO EMVs; cell expression of Beclin-1 (53.8±6.4 vs 36.6±3.6 AU), p62 (34.0±0.8 vs 16.9±1.2 AU) and LC3BII/LC3BI (15.0±0.1 vs 7.5±0.8 AU) were significantly elevated in cells treated with TMAO vs control EMVs. Conclusions: TMAO-generated EMVs adversely affect major functional characteristics of endothelial cells potentially contributing to the proatherogenic profile of TMAO.