tbuckley/cabot-search huggingface dataset:
Science and Feminism
Journal: JAMA (2000)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors: identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate cellular stress
Authors: Milton Packer
Journal: Cardiovascular Research (2020)

Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of serious heart failure events, even though SGLT2 is not expressed in the myocardium. This cardioprotective benefit is not related to an effect of these drugs to lower blood glucose, promote ketone body utilization or enhance natriuresis, but it is linked statistically with their action to increase haematocrit. SGLT2 inhibitors increase both erythropoietin and erythropoiesis, but the increase in red blood cell mass does not directly prevent heart failure events. Instead, erythrocytosis is a biomarker of a state of hypoxia mimicry, which is induced by SGLT2 inhibitors in manner akin to cobalt chloride. The primary mediators of the cellular response to states of energy depletion are sirtuin-1 and hypoxia-inducible factors (HIF-1α/HIF-2α). These master regulators promote the cellular adaptation to states of nutrient and oxygen deprivation, promoting mitochondrial capacity and minimizing the generation of oxidative stress. Activation of sirtuin-1 and HIF-1α/HIF-2α also stimulates autophagy, a lysosome-mediated degradative pathway that maintains cellular homoeostasis by removing dangerous constituents (particularly unhealthy mitochondria and peroxisomes), which are a major source of oxidative stress and cardiomyocyte dysfunction and demise. SGLT2 inhibitors can activate SIRT-1 and stimulate autophagy in the heart, and thereby, favourably influence the course of cardiomyopathy. Therefore, the linkage between erythrocytosis and the reduction in heart failure events with SGLT2 inhibitors may be related to a shared underlying molecular mechanism that is triggered by the action of these drugs to induce a perceived state of oxygen and nutrient deprivation.
Opening of endothelial cell–cell contacts due to sonoporation
Authors: Inés Beekers, Merel Vegter, Kirby R. Lattwein, Frits Mastik, Robert Beurskens, Antonius F.W. van der Steen, Nico de Jong, Martin D. Verweij, Klazina Kooiman
Journal: Journal of Controlled Release (2020)

Ultrasound insonification of microbubbles can locally increase vascular permeability to enhance drug delivery. To control and optimize the therapeutic potential, we need to better understand the underlying biological mechanisms of the drug delivery pathways. The aim of this in vitro study was to elucidate the microbubble-endothelial cell interaction using the Brandaris 128 ultra-high-speed camera (up to 25 Mfps) coupled to a custom-built Nikon confocal microscope, to visualize both microbubble oscillation and the cellular response. Sonoporation and opening of cell-cell contacts by single αVβ3-targeted microbubbles (n = 152) was monitored up to 4 min after ultrasound insonification (2 MHz, 100-400 kPa, 10 cycles). Sonoporation occurred when microbubble excursion amplitudes exceeded 0.7 μm. Quantification of the influx of the fluorescent model drug propidium iodide upon sonoporation showed that the size of the created pore increased for larger microbubble excursion amplitudes. Microbubble-mediated opening of cell-cell contacts occurred as a cellular response upon sonoporation and did not correlate with the microbubble excursion amplitude itself. The initial integrity of the cell-cell contacts affected the susceptibly to drug delivery, since cell-cell contacts opened more often when cells were only partially attached to their neighbors (48%) than when fully attached (14%). The drug delivery outcomes were independent of nonlinear microbubble behavior, microbubble location, and cell size. In conclusion, by studying the microbubble-cell interaction at nanosecond and nanometer resolution the relationship between drug delivery pathways and their underlying mechanisms was further unraveled. These novel insights will aid the development of safe and efficient microbubble-mediated drug delivery.
Long-Term Outcomes in Women and Men Following Percutaneous Coronary Intervention
Authors: Ioanna Kosmidou, Martin B. Leon, Yiran Zhang, Patrick W. Serruys, Clemens von Birgelen, Pieter C. Smits, Ori Ben-Yehuda, Björn Redfors, Mahesh V. Madhavan, Akiko Maehara, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)
Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial
Authors: J.-H. Kim, I. Kim, C.K. Kang, K.-I. Jun, S.H. Yoo, J.Y. Chun, J. Jung, Y.J. Kim, D.Y. Kim, H.B. Jo, D.Y. Kim, Y. Koh, D.-Y. Shin, J. Hong, N.J. Kim, S.-S. Yoon, T.S. Kim, W.B. Park, M.-d. Oh
Journal: Clinical Microbiology and Infection (2020)
Association of Video Game Use With Body Mass Index and Other Energy-Balance Behaviors in Children
Authors: William Goodman, Sarah E. Jackson, Ethna McFerran, Richard Purves, Ian Redpath, Rebecca J. Beeken
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Childhood obesity is one of the biggest public health threats facing the UK, and video game use is considered a risk behavior for obesity among children. However, few studies have explored the prospective association between video game use and body mass index (BMI) or the potential mediators of this association. <h3>Objectives</h3> To investigate whether a longer-term association exists between video game use at a young age and BMI SD score in later years, independent of television use, and to ascertain whether this association is mediated by other energy-balance behaviors. <h3>Design, Setting, and Participants</h3> This cohort study is a secondary analysis of data from the Millennium Cohort Study, a nationally representative sample of children who were born in the UK between September 1, 2000, and January 31, 2002, that focused on data collected when the children were aged 5, 7, 11, and 14 years. Data for all variables, except BMI, were provided by parental or caregiver reporting if the children were younger than 14 years of age. At age 14 years, the children self-reported their own behavior. Initial data analysis was conducted between September 18, 2018, and September 28, 2018, with supplementary analyses conducted from October 7, 2019, to November 22, 2019. <h3>Main Outcomes and Measures</h3> The main outcome variable was BMI SD scores, with video game use as the exposure variable of interest. Physical activity, bedtime regularity, sugar-sweetened beverage consumption, and high-calorie food consumption were included as potential mediating behaviors. <h3>Results</h3> The full sample comprised 16 376 children and had a nearly equal number of boys (8393 [51.3%]) and girls (7983 [48.7%]). Every 1 SD increase in the number of hours of video game use at age 5 years was associated with a β = 0.018 higher BMI SD score at age 14 years (95% CI, 0.004-0.032). A small partial mediation of this association was found (direct association: β = 0.017 [95% CI, 0.003-0.031]; indirect association: β = 0.0011 [95% CI, 0.0003-0.0019]), suggesting that irregular bedtimes and higher consumption of sugar-sweetened beverages were mediators. The mediation model accounted for 36.7% (95% CI, 35.5-37.8) of the variance of the BMI SD score at age 14 years. <h3>Conclusions and Relevance</h3> Results of this study suggest a small (and not clinically meaningful) association between video game use in early childhood and higher BMI in later years, which may be mediated by irregular bedtimes and higher consumption of sugar-sweetened beverages. Future interventions to prevent childhood obesity should incorporate health promotion in mainstream video games to target children most at risk because of their high level of video game use.
Abstract 14940: Association of MCP-1, hsCRP, Neopterin, MMP-9 and NT-proBNP With Coronary Heart Disease Risk in Patients With Prior Stroke or Transient Ischemic Attack. Results of the Analysis of 13 Biomarkers From the SPARCL Trial
Authors: Peter Ganz, Pierre Amarenco, Larry B Goldstein, Henrik Sillesen, Weihang Bao, Gregory M Preston, K M Welch
Journal: Circulation (2013)

Background: Patients with prior strokes or transient ischemic attacks (TIAs) are at high risk of coronary heart disease (CHD). Established risk factors do not fully identify this high risk. The Str...
The orphan receptor tyrosine kinase Ror1 mediates canonical Wnt signaling and is required for NSCLC cell survival in vitro and in vivo.
Authors: Anna Galkin, Karin Forster, Peter Vogt, Markus Warmuth
Journal: Cancer Research (2008)

4946  Deregulation of the Wnt mediated self-renewal, proliferation and differentiation mechanisms is associated with malignant transformation and tumor growth. Insights into the key regulators of the pathway may help provide novel therapeutic strategies, specifically targeting the self-renewal pathways in cancer. The receptor tyrosine-kinase like orphan receptor-1 (Ror1) plays a crucial role in developmental morphogenesis. Ror1 over-expression in B-CLL patient samples and a number of cancer cell lines prompted an investigation into its biological role in cancer. Using 293T cells stably expressing the SuperTopFlash (STF) reporter system, we identified Ror1 as a mediator of canonical Wnt3a signaling. Although, Ror1 expression did not influence canonical Wnt pathway activation to the same extent as either LRP6 or Dvl3 over-expression, it was observed to be a positive regulator of the pathway, activating the STF reporter 2.5 -7 fold, in a dose-dependent manner. Mutant Ror-1 constructs, lacking the frizzled-like domain or the entire intracellular domain were unable to enhance STF reporter activation to the same extent as the full-length receptor. In addition, co-expression of Ror1 with Dvl3 resulted in a stronger activation of the STF reporter than by either construct alone, demonstrating synergy between the two proteins and canonical Wnt pathway activation. Using Ror1 targeting shRNA we assessed the role of endogenous Ror1 receptors in Wnt3a canonical signaling. Ror1 shRNA inhibited Wnt3a mediated activation of the STF reporter to the same extent as LRP6 shRNA. STF reporter activation directly correlated with the levels of Ror1/LRP6 surface expression, suggesting that Ror1 is as equally important for canonical Wnt signal transduction as LRP6. Effects of stable Ror1 knockdown was then evaluated in A549 and H1299 NSCLC cell lines, expressing high levels of endogenous Ror1. In both A549 and H1299 cells, Ror1 shRNA decreased cell proliferation and induced cell cycle arrest in vitro. An even stronger effect of Ror1 knockdown was observed in vivo, where infection of A549 cells with Ror1 shRNA completely abrogated tumor growth, as compared to non-targeting control shRNA. These data demonstrate Ror1 to be a positive regulator of canonical Wnt signaling and crucial for NSCLC cell survival in vitro and in vivo.
Abstract 12294: Cross Talk Between Arterial Stiffening and Myocardial Fibrosis in Patients With Heart Failure: The Role of Galectin-3
Authors: Evangelos Oikonomou, Sotiris Tsalamandris, Georgia Vogiatzi, Dimitrios Karlis, Gerasimos Siasos, Christina Chrysohoou, George Marinos, Vasiliki Mystakidou, George Charalambous, Evangelia Kouskouni, Dimitris Tousoulis
Journal: Circulation (2018)

Introduction: Cardiac performance depends on optimum ventriculoarterial coupling which is impaired in patients with heart failure (HF). Galectin-3 is a mediator of myocardial fibrosis and remodelin...
Validating the Importance of Positive Childhood Experiences on Adult Mental Health
Authors: Cynthia L. Gong, Leah Yieh, Joel W. Hay
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Past, present, and future of anti‐IgE biologics
Authors: Pascal Guntern, Alexander Eggel
Journal: Allergy (2020)

About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances, scientists have started inventing strategies to block its pathophysiological activity in 1986. The initial concept of specific IgE targeting through the use of anti-IgE antibodies has gained a lot of momentum and within a few years independent research groups have reported successful generation of first murine monoclonal anti-IgE antibodies. Subsequent generation of optimized chimeric and humanized versions of these antibodies has paved the way for the development of therapeutic anti-IgE biologicals as we know them today. With omalizumab, there is currently still only one therapeutic anti-IgE antibody approved for the treatment of allergic conditions. Since its application is limited to the treatment of moderate-to-severe persistent asthma and chronic spontaneous urticaria, major efforts have been undertaken to develop alternative anti-IgE biologicals that could potentially be used in a broader spectrum of allergic diseases. Several new drug candidates have been generated and are currently assessed in pre-clinical studies or clinical trials. In this review, we highlight the molecular properties of past and present anti-IgE biologicals and suggest concepts that might improve treatment efficacy of future drug candidates.
PCSK9 Inhibition with alirocumab increases the catabolism of lipoprotein(a) particles in statin-treated patients with elevated lipoprotein(a)
Authors: Gerald F. Watts, Dick C. Chan, Jing Pang, Louis Ma, Qidi Ying, Shashi Aggarwal, Santica M. Marcovina, P. Hugh R. Barrett
Journal: Metabolism (2020)
Helen Salisbury: Planning for the peak
Authors: Helen Salisbury
Journal: BMJ (2020)

This week we’ve been climbing a very steep learning curve about coronavirus infection. With so many unknowns I feel up in the air, as though my toes are barely touching the safe ground of my medical training. I’m experienced, fairly confident, and—until this week—not in the habit of taking home worries about my patients. Now, the more I read, the less certain I feel about some of my advice. When “outdated” refers to guidance based on China’s experience and published a month ago, being up to date takes on a whole new meaning. …
Mitochondria and T2D: Role of Autophagy, ER Stress, and Inflammasome
Authors: Milagros Rocha, Nadezda Apostolova, Ruben Diaz-Rua, Jordi Muntane, Victor M. Victor
Journal: Trends in Endocrinology and Metabolism (2020)

Type 2 diabetes (T2D) is one of the main current threats to human health. Both T2D and its numerous clinical complications are related to mitochondrial dysfunction and oxidative stress. Over the past decade, great progress has been made in extending our knowledge about the signaling events regulated by mitochondria. However, the links among mitochondrial impairment, oxidative stress, autophagy, endoplasmic reticulum (ER) stress, and activation of the inflammasome still need to be clarified. In light of this deficit, we aim to provide a review of the existing literature concerning the complicated crosstalk between mitochondrial impairment, autophagy, ER stress, and the inflammasome in the molecular pathogenesis of T2D.
Abstract 11816: Dysregulation of Intracellular Calcium in Diabetic Cardiomyopathy is Improved by Whole Body Periodic Acceleration (pGz)
Authors: Jose R Lopez, Arkady Uryash, Jose A Adams
Journal: Circulation (2018)

Introduction: More than 422 million people worldwide suffer from diabetes mellitus (DM). Diabetes and other metabolic conditions characterized by elevated blood glucose constitute important risk fa...
Association Between Endoscopist Annual Procedure Volume and Colonoscopy Quality: Systematic Review and Meta-analysis
Authors: Nauzer Forbes, Devon J. Boyne, Matthew S. Mazurek, Robert J. Hilsden, R. Liam Sutherland, Joy Pader, Yibing Ruan, Abdel Aziz Shaheen, Clarence Wong, Mubasiru Lamidi, Diane L. Lorenzetti, Darren R. Brenner, Steven J. Heitman
Journal: Clinical Gastroenterology and Hepatology (2020)

In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), indicators for assessing colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between annual colonoscopy volume and ADR, CIR, AEs, or PCCRC.We searched publication databases through March 2019 for studies assessing the relationship between annual colonoscopy volume and outcomes, including ADR, CIR, AEs, or PCCRC. Pooled odds ratios (ORs) were calculated using DerSimonian and Laird random effects models. Sensitivity analyses were performed to assess for potential methodological or clinical factors associated with outcomes.We performed a systematic review of 9235 initial citations, generating 27 retained studies comprising 11,276,244 colonoscopies. There was no association between procedural volume and ADR (OR, 1.00; 95% CI, 0.98-1.02 per additional 100 annual procedures). CIR improved with each additional 100 annual procedures (OR, 1.17; 95% CI, 1.08-1.28). There was a non-significant trend toward decreased overall AEs per additional 100 annual procedures (OR, 0.95; 95% CI, 0.90-1.00). There was considerable heterogeneity among most analyses.In a systematic review and meta-analysis, we found higher annual colonoscopy volumes to correlate with higher CIR, but not with ADR or PCCRC. Trends toward fewer AEs were associated with higher annual colonoscopy volumes. There are few data available from endoscopists who perform fewer than 100 annual colonoscopies. Studies are needed on extremes in performance volumes to more clearly elucidate associations between colonoscopy volumes and outcomes.
Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia
Authors: Hanren Dai, Zhiqiang Wu, Hejin Jia, Chuan Tong, Yelei Guo, Dongdong Ti, Xiao Han, Yang Liu, Wenying Zhang, Chunmeng Wang, Yajing Zhang, Meixia Chen, Qingming Yang, Yao Wang, Weidong Han
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Despite the impressive complete remission (CR) induced by CD19 CAR-T cell therapy in B-ALL, the high rate of complete responses is sometimes limited by the emergence of CD19-negative leukemia. Bispecific CAR-modified T cells targeting both CD19 and CD22 may overcome the limitation of CD19-negative relapse. Methods We here report the design of a bispecific CAR simultaneous targeting of CD19 and CD22. We performed a phase 1 trial of bispecific CAR T cell therapy in patients with relapsed/refractory precursor B-ALL at a dose that ranged from 1.7 × 10 6 to 3 × 10 6 CAR T cells per kilogram of body weight. Results We demonstrate bispecific CD19/CD22 CAR T cells could trigger robust cytolytic activity against target cells. MRD-negative CR was achieved in 6 out of 6 enrolled patients. Autologous CD19/CD22 CAR T cells proliferated in vivo and were detected in the blood, bone marrow, and cerebrospinal fluid. No neurotoxicity occurred in any of the 6 patients treated. Of note, one patient had a relapse with blast cells that no longer expressed CD19 and exhibited diminished CD22 site density approximately 5 months after treatment. Conclusion In brief, autologous CD19/CD22 CAR T cell therapy is feasible and safe and mediates potent anti-leukemic activity in patients with relapsed/refractory B-ALL. Furthermore, the emergence of target antigen loss and expression downregulation highlights the critical need to anticipate antigen escape. Our study demonstrates the reliability of bispecific CD19/CD22 CAR T cell therapy in inducing remission in adult patients with relapsed/refractory B-ALL. Trial registration ClinicalTrials.gov identifier: NCT03185494 .
Delivery of thymoquinone through hyaluronic acid-decorated mixed Pluronic® nanoparticles to attenuate angiogenesis and metastasis of triple-negative breast cancer
Authors: Saurav Bhattacharya, Avijit Ghosh, Santanu Maiti, Manisha Ahir, Gouranga H. Debnath, Payal Gupta, Mousumi Bhattacharjee, Swatilekha Ghosh, Sreya Chattopadhyay, Prasun Mukherjee, Arghya Adhikary
Journal: Journal of Controlled Release (2020)
HEART WITH SOME GUTS: TRAUMA INDUCED INTRA-PERICARDIAL DIAPHRAGMATIC HERNIA
Authors: Hamza Hafeez, Sharath Rajagopalan, Abdul Haseeb, Mirza Mujadil Ahmad, Mousa Thalji, Najam Saqib, Muhammad Siddique Pir, Sangeeta Prabhakar Bhat, Sreelatha Naik
Journal: Journal of the American College of Cardiology (2020)
Functional Genomics of the Pediatric Obese Asthma Phenotype Reveal Enrichment of Rho-GTPase Pathways
Authors: Deepa Rastogi, Andrew D. Johnston, John Nico, Lip Nam Loh, Yurydia Jorge, Masako Suzuki, Fernando Macian, John M. Greally
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Obesity-related asthma disproportionately affects minority children and is associated with nonatopic T-helper type 1 (Th1) cell polarized inflammation that correlates with pulmonary function deficits. Its underlying mechanisms are poorly understood.
KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer
Authors: Hunain Alam, Ming Tang, Mayinuer Maitituoheti, Shilpa S. Dhar, Manish Kumar, Chae Young Han, Chandrashekar R. Ambati, Samir B. Amin, Bingnan Gu, Tsai-Yu Chen, Yu-Hsi Lin, Jichao Chen, Florian L. Muller, Nagireddy Putluri, Elsa R. Flores, Francesco J. DeMayo, Laura Baseler, Kunal Rai, Min Gyu Lee
Journal: Cancer Cell (2020)