tbuckley/cabot-search huggingface dataset:
Red Blood Cell–Derived Nitric Oxide Bioactivity and Hypoxic Vasodilation
Authors: Harald H.H.W. Schmidt, Martin Feelisch
Journal: Circulation (2019)

ypoxic vasodilation is a conserved adaptive response that enables regional increases in blood flow to compensate for an acute reduction in oxygen delivery to tissues.Although already discovered in the 19th century, mechanistic details of the underpinning signaling pathways have remained unresolved.Skeletal muscle blood flow and vascular conductance are more closely related to changes in arterial oxygen content than the partial pressure of oxygen, suggesting that the mechanisms involved in determining blood vessel diameter in the tissue are sensitive to changes in oxygen content.Because the latter is directly related to hemoglobin mass and oxygenation, red blood cells (RBCs) may be involved in sensing the relationship between tissue oxygen demand and convective oxygen delivery when coupled to a transduction pathway capable of modulating blood flow. S-NITROSO HEMOGLOBIN AND THE S-NITROSOTHIOL STORMIn 1996, Stamler's group introduced a concept (Figure ) that was as novel and intriguing as it was elegant, suggesting that RBCs have their own vasodilator mechanism aboard while traveling the circulation, 1 combining a capturing, preservation, and release mechanism for nitric oxide (NO) that is linked to hypoxic vasodilation 2 and platelet inhibition. 3Apart from RBCs being able to release NO, mechanistic details changed over time, and not all findings were reproducible by other groups. 4n this issue of Circulation, Sun et al 5 present negative data from a joint effort by an international team of investigators that puts an end to the notion that Cysβ93 S-nitrosothiol is involved in the process of hypoxic vasodilation.Sun et al's data, however, are also positive in the sense that they confirm the ability of RBCs to export NO bioactivity. 5Is this the end of the S-nitroso hemoglobin story?Probably not, but most certainly for Cysβ93 S-nitrosothiol as a critical link. HYPOXIC VASODILATIONPrevious studies described an association between hypoxic vasodilation and the release of NO from isolated vascular tissue and cultured endothelial cells, and later demonstrated that NO is involved in hypoxic vasodilation in the human forearm.Of note, hypoxia has opposing effects on vascular diameter in the systemic circulation and the lung, where it causes vasoconstriction.This von Euler-Liljestrand mechanism matches regional pulmonary ventilation to perfusion, whereas regional vasodilation protects tissues in the face of reduced oxygen delivery.Enhanced NO production is a universal response to hypoxia, 6 and elevated concentrations of NO metabolites
Nanoparticle diffusion in spontaneously expectorated sputum as a biophysical tool to probe disease severity in COPD
Authors: Jane F. Chisholm, Siddharth K. Shenoy, Julie K. Shade, Victor Kim, Nirupama Putcha, Kathryn A. Carson, Robert Wise, Nadia N. Hansel, Justin S. Hanes, Jung Soo Suk, Enid Neptune
Journal: European Respiratory Journal (2019)

Perturbations in airway mucus properties contribute to lung function decline in patients with chronic obstructive pulmonary disease (COPD). While alterations in bulk mucus rheology have been widely explored, microscopic mucus properties that directly impact on the dynamics of microorganisms and immune cells in the COPD lungs are yet to be investigated. We hypothesised that a tightened mesh structure of spontaneously expectorated mucus ( i.e. sputum) would contribute to increased COPD disease severity. Here, we investigated whether the mesh size of COPD sputum, quantified by muco-inert nanoparticle (MIP) diffusion, correlated with sputum composition and lung function measurements. The microstructure of COPD sputum was assessed based on the mean squared displacement (MSD) of variously sized MIPs measured by multiple particle tracking. MSD values were correlated with sputum composition and spirometry. In total, 33 samples collected from COPD or non-COPD individuals were analysed. We found that 100 nm MIPs differentiated microstructural features of COPD sputum. The mobility of MIPs was more hindered in sputum samples from patients with severe COPD, suggesting a tighter mucus mesh size. Specifically, MSD values inversely correlated with lung function. These findings suggest that sputum microstructure may serve as a novel risk factor for COPD progression and severity.
Digital Breast Tomosynthesis for Women Older Than 70 Years
Authors: Melissa A. Durand, Liane Philpotts
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia by Inhibition of Ca <sup>2+</sup> /Calmodulin-Dependent Kinase II
Authors: Vassilios J. Bezzerides, Ana Caballero, Suya Wang, Yulan Ai, Robyn J. Hylind, Fujian Lu, Danielle A. Heims-Waldron, Kristina D. Chambers, Donghui Zhang, Dominic J. Abrams, William T. Pu
Journal: Circulation (2019)

Catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited cardiac arrhythmia characterized by adrenergically triggered arrhythmias, is inadequately treated by current standard of care. Ca2+/calmodulin-dependent protein kinase II (CaMKII), an adrenergically activated kinase that contributes to arrhythmogenesis in heart disease models, is a candidate therapeutic target in CPVT. However, translation of CaMKII inhibition has been limited by the need for selective CaMKII inhibition in cardiomyocytes. Here, we tested the hypothesis that CaMKII inhibition with a cardiomyocyte-targeted gene therapy strategy would suppress arrhythmia in CPVT mouse models.We developed AAV9-GFP-AIP, an adeno-associated viral vector in which a potent CaMKII inhibitory peptide, autocamtide-2-related inhibitory peptide [AIP], is fused to green fluorescent protein (GFP) and expressed from a cardiomyocyte selective promoter. The vector was delivered systemically. Arrhythmia burden was evaluated with invasive electrophysiology testing in adult mice. AIP was also tested on induced pluripotent stem cells derived from patients with CPVT with different disease-causing mutations to determine the effectiveness of our proposed therapy on human induced pluripotent stem cell-derived cardiomyocytes and different pathogenic genotypes.AAV9-GFP-AIP was robustly expressed in the heart without significant expression in extracardiac tissues, including the brain. Administration of AAV9-GFP-AIP to neonatal mice with a known CPVT mutation (RYR2R176Q/+) effectively suppressed ventricular arrhythmias induced by either β-adrenergic stimulation or programmed ventricular pacing, without significant proarrhythmic effect. Intravascular delivery of AAV9-GFP-AIP to adolescent mice transduced ≈50% of cardiomyocytes and was effective in suppressing arrhythmia in CPVT mice. Induced pluripotent stem cell-derived cardiomyocytes derived from 2 different patients with CPVT with different pathogenic mutations demonstrated increased frequency of abnormal calcium release events, which was suppressed by a cell-permeable form of AIP.This proof-of-concept study showed that AAV-mediated delivery of a CaMKII peptide inhibitor to the heart was effective in suppressing arrhythmias in a murine model of CPVT. CaMKII inhibition also reversed the arrhythmia phenotype in human CPVT induced pluripotent stem cell-derived cardiomyocyte models with different pathogenic mutations.
Mortality From Falls Among US Adults Aged 75 Years or Older, 2000-2016
Authors: Klaas A. Hartholt, Robin Lee, Elizabeth R. Burns, Ed F. van Beeck
Journal: JAMA (2019)

Teresa Liu-Ambrose, PT, PhD; Jennifer C. Davis, PhD; John R. Best, PhD; Larry Dian, MD; Kenneth Madden, MD; Wendy Cook, MD; Chun Liang Hsu, PhD; Karim M. Khan, MD, PhD
60 Tailored therapy for rescue treatment of helicobacter pylori infection
Authors: D Brennan, M Hussey, D Tighe, C O’Morain, S Smith, D McNamara
Journal: Gut (2017)

Background  Due to increasing prevalence of antibiotic resistant Helicobacter pylori, the number of patients who require rescue treatment (after >1 failed eradication attempts) is increasing. First-line treatment for H. pylori is not standardised, therefore it’s difficult to recommend a specific rescue treatment. Prescribing a tailored regimen based on antibiotic sensitivities upon first eradication failure may be most effective.  Aim  To examine the efficacy of a tailored regimen based on antimicrobial susceptibility as a rescue treatment for H. pylori.  Method  Patients previously treated for H. pylori and undergoing endoscopy were prospectively recruited. Biopsies from H. pylori-positive patients (CLO test) were processed for sensitivity testing. Patients received treatment based on antibiotic sensitivities, for 7/14 days. A follow-up breath test was performed 8 weeks post-treatment.  Results  Of 881 gastroscopies done between April 2013- February 2017, 190 (22%) were H. pylori positive. Of these, 76 (40%) were previously treated: 41 (54%) received one prior treatment and 35 (46%) received >1. To date, 44 (58%) patients have completed the study; 20 (45%) received levofloxacin triple therapy; 10 (23%) a PPI and 2 antibiotics based on their sensitivities; 10 (23%) bismuth quadruple and 4 (9%) clarithromycin triple therapy. The efficacy of tailored treatment by intention-to-treat and per protocol analysis was poor, at 47.3% (26/55) and 59.1% (26/44) respectively. Patients who received one previous treatment were significantly more likely to achieve eradication than those who received >1 previous treatment (76.2% vs 43.5%, p=0.04).  Conclusions  Rescue eradication rates are disappointing and emphasise the importance of eradicating H. pylori infection the first time round.
Outpatient Stem Cell Mobilization with Low and Intermediate Dose Cyclophosphamide Is a Safe and Effective Procedure in Newly Diagnosed Multiple Myeloma Patients Eligible for Stem Cell Transplantation
Authors: Alessandra Pompa, Laura Paris, Francesca Guidotti, Valeria Ferla, Monica Galli, Alessandro Rambaldi, Luca Baldini, Agostino Cortelezzi
Journal: Blood (2017)
Abstract 15376: Non-Invasive Assessment of Cardiac Output: A Method Whose Time Has Come?
Authors: Elizabeth A Hardin, Douglas Stoller, Michinari Hieda, Satyam Sarma, Ben Levine
Journal: Circulation (2017)

Background: Accurate assessment of cardiac output (CO) is critical to the diagnosis and management of various cardiac disease states; however, the clinical standards of direct Fick and thermodiluti...
Sure Start cut child admissions and health inequalities, report finds
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Sure Start, a UK government programme designed to support children’s learning, health, and development, has delivered major health benefits for children in poorer neighbourhoods, a report from the Institute for Fiscal Studies concludes.1

Researchers analysed Sure Start’s impact on children born in the period from its inception in 1999 to its peak in 2009-10. They found that it had reduced the likelihood of hospital admission among children of …
Chronic cough: ATP, afferent pathways and hypersensitivity
Authors: Richard D. Turner, Surinder S. Birring
Journal: European Respiratory Journal (2019)

<b>New evidence from tussive challenges and the P2X inhibitor gefapixant strengthens ATP as a driver of chronic cough. Cough responses to other irritants probably involve a separate peripheral activation pathway. Hypersensitivity may be due to distinct processes again.</b>http://bit.ly/2YR6MuZ
Abstract 13985: Anti-inflammatory Cytokine Interleukin-35 Inhibits Lipopolysaccharide-induced Vascular Inflammation
Authors: Xiaojin Sha, Shu Meng, Xinyuan Li, David Pascual, Hong Wang, Xiao-feng Yang
Journal: Circulation (2013)

Interleukin-35 (IL-35), consisting of two subunits, Epstein-Barr virus-induced gene 3 (EBI3) and p35, is a novel anti-inflammatory responsive cytokine in IL-12 cytokine family. IL-35 is produced by...
Former NHS England director is sentenced for voyeurism
Authors: Clare Dyer
Journal: BMJ (2019)

Jonathan Fielden, the former deputy medical director of NHS England, has been given a five months suspended prison sentence after admitting watching a 15 year old girl showering through a hole in the ceiling at a private home.1

Sentencing him at Luton Crown Court, Judge Richard Foster told him, “It’s tragic to see you, a man of such brilliance in your career, a hardworking man at the pinnacle of your career, responsible for a substantial part of the NHS budget, to fall from grace in the way you have because of what you stupidly did.” …
Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer
Authors: Audrey Simonaggio, Jean Marie Michot, Anne Laure Voisin, Jérome Le Pavec, Michael Collins, Audrey Lallart, Geoffray Cengizalp, Aurore Vozy, Ariane Laparra, Andréa Varga, Antoine Hollebecque, Stéphane Champiat, Aurélien Marabelle, Christophe Massard, Olivier Lambotte
Journal: JAMA Oncology (2019)

Although immune checkpoint inhibitors (ICIs), such as anti-PD-1 (programmed cell death 1) or anti-PD-L1 (programmed cell death 1 ligand 1), have proved effective in treating many cancers, patients receiving ICIs may experience immune-related adverse events (irAEs). Little evidence exists on the safety of resuming these treatments after an irAE.
Falls in Older Adults
Authors: Marco Pahor
Journal: JAMA (2019)

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
Phosphorylation and activation of CDCA8 by aurora kinase B plays a significant role in human lung carcinogenesis: A new pathway of oncogenesis as a molecular therapeutic target
Authors: Yataro Daigo, Satoshi Hayama, Daizaburo Hirata, Eiju Tsuchiya, Yusuke Nakamura
Journal: Cancer Research (2008)

4238  Lung cancer is one of the most common fatal cancers in the world. A number of molecular targets and biomarkers for cancer therapy have been reported, but the number of patients responding well is still very limited, and only a very small number of practical biomarkers are presently available for the selection of treatment modalities that can provide survival benefits. To identify molecules involved in new pathways of oncogenesis, which might serve as diagnostic biomarkers and/or targets for the development of novel molecular therapies, we have been screening genes encoding oncoproteins that are frequently over-expressed in lung cancers, but not in normal organs, using cDNA microarrays representing 32,256 genes coupled with the purification of tumor cells from 101 patients by laser microdissection. As a result of this process, we detected in the majority of lung-cancers co-transactivation of cell-division-associated 8 (CDCA8) and aurora kinase B (AURKB), which are components of the vertebrate chromosomal passenger complex that are considered to be key regulators of mitotic events. Immunohistochemical analysis of 273 lung-cancer tissue microarrays demonstrated that CDCA8 and AURKB were co-activated in most cases, and that over-expression of CDCA8 and AURKB was significantly associated with poor prognosis for lung-cancer patients (P
Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study
Authors: Sara A. Hurvitz, Miguel Martin, Kyung Hae Jung, Chiun-Sheng Huang, Nadia Harbeck, Vicente Valero, Daniil Stroyakovskiy, Hans Wildiers, Mario Campone, Jean-François Boileau, Peter A. Fasching, Karen Afenjar, Gonzalo Spera, Vanesa Lopez-Valverde, Chunyan Song, Peter Trask, Thomas Boulet, Joseph A. Sparano, W. Fraser Symmans, Alastair M. Thompson, Dennis Slamon
Journal: Journal of Clinical Oncology (2019)

The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4%
Abstract 18575: Comparative Effectiveness of Adolescent Cholesterol Screening and Treatment Strategies
Authors: Sarah D de Ferranti, Angie Mae Rodday, R. Christopher Sheldrick, Laurel K Leslie, John B Wong
Journal: Circulation (2017)

Introduction: Cholesterol screening and treatment in adolescents and young adults (AYAs) may improve cardiovascular disease (CVD) outcomes from lifelong high cholesterol as seen in familial hyperch...
The Precision of Evidence Needed to Practice “Precision Medicine”
Authors: David J. Hunter, Dan L. Longo
Journal: New England Journal of Medicine (2019)

In July 2018, the Journal published the results of TAILORx (Trial Assigning Individualized Options for Treatment).1 This randomized trial conducted by Sparano et al. showed the noninferiority of endocrine therapy to chemoendocrine therapy with respect to invasive disease–free survival among women with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary node–negative breast cancer who had a recurrence score (based on a 21-gene assay) of 11 to 25 (scores range from 0 to 100, with higher scores predicting a higher risk of distant recurrence). This was the primary objective of the trial; interactions on the multiplicative scale between randomized treatment . . .
Rationale and design for the development of a novel nitroxyl donor in patients with acute heart failure
Authors: G. Michael Felker, Maria Borentain, John G. Cleland, Mary M. DeSouza, Paul D. Kessler, Christopher M. O'Connor, Dietmar Seiffert, John R. Teerlink, Adriaan A. Voors, John J.V. McMurray
Journal: European Journal of Heart Failure (2019)
Effectiveness of a Best Practice Alert to Reduce Telemetry Orders
Authors: William M. Garneau, Amy M. Knight, Amit K. Pahwa
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Vaccination over Parental Objection — Should Adolescents Be Allowed to Consent to Receiving Vaccines?
Authors: Ross D. Silverman, Douglas J. Opel, Saad B. Omer
Journal: New England Journal of Medicine (2019)

Vaccination over Parental Objection Parents’ resistance to vaccination is leaving more children vulnerable to measles and other preventable illnesses. Most states, however, don’t authorize adolesce...