tbuckley/cabot-search huggingface dataset:
Moving Beyond Using the Term <i>Poor Prognosis </i>in Children With Severe Neurological Impairment
Authors: Jori Bogetz, Benjamin S. Wilfond, Aaron Wightman
Journal: JAMA Pediatrics (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 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
TATTON expansion cohorts: A phase Ib study of osimertinib plus savolitinib in patients (pts) with EGFR-mutant, MET-positive NSCLC following disease progression on a prior EGFR-TKI
Authors: J.-Y. Han, L.V. Sequist, M.-J. Ahn, B.C. Cho, H. Yu, S.-W. Kim, J.C.-H. Yang, J.S. Lee, W.-C. Su, D. Kowalski, S. Orlov, M. Cantarini, R.B. Verheijen, A. Mellemgaard, P. Frewer, X. Ou, G. Oxnard
Journal: Annals of Oncology (2019)
Abstract 17067: MAVERICK-HCM: Phase 2 Randomized, Multi-Center, Double-Blind, Placebo-Controlled Concentration-Guided Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
Authors: Stephen Heitner, Andrew Wang, Daniel Jacoby, Steven Lester, Timothy Carlson, David Zhang, Amy Sehnert, Carolyn Ho
Journal: Circulation (2018)

Introduction: Hypertrophic cardiomyopathy (HCM) carries substantial lifelong morbidity. Mutations in sarcomeric proteins that lead to HCM cause excess contractility, poor relaxation, and inefficient energy utilization. Although obstructive physiology is a prominent feature of disease, approximately 30% of HCM patients experience symptoms in the context of non-obstructive HCM (nHCM). Management options are extremely limited with little other than cardiac transplantation to offer severely affected patients. Mavacamten (MAVA), a first-in-class small molecule, is a selective modulator of cardiac myosin that inhibits the cardiac myosin ATPase to reversibly attenuate cardiac contractility. In addition to its effects on contractility, MAVA has been shown to improve LV compliance in preclinical and clinical studies. The Phase 2 MAVERICK-HCM study is designed to evaluate safety and tolerability, and to provide pilot data on the effects of MAVA on biomarkers, cardiac function, and exercise capacity in nHCM. Methods: This double-blind study will enroll 60 individuals with nHCM (Left ventricular outflow tract gradient &lt;30 mmHg; resting or provoked), NYHA Class II or III, and LVEF ≥55%. Subjects will be randomized 1:1:1 to one of two target plasma drug concentrations (Group 1: ~200 ng/mL and Group 2: ~500 ng/mL) or placebo for 16 weeks. The starting dose of MAVA is 5 mg, with one-step dose titration at Week 6 based on plasma drug concentration. Predefined criteria, including LVEF, will guide study drug discontinuation if indicated. Cardiopulmonary exercise testing will be performed at baseline and Week 16 to assess the impact on exercise capacity. The primary endpoint is the frequency and severity of treatment-emergent adverse events. The study design also includes multiple secondary endpoints including echocardiographic measures of diastolic function, NT-proBNP levels, patient reported outcomes, and physical activity by wearable accelerometer. An independent data monitoring committee will oversee safety. Conclusions: MAVERICK-HCM is testing a novel therapy to improve symptom burden in nHCM; a patient cohort currently lacking effective treatment. By targeting a core molecular mechanism of disease, MAVA has the potential to alter natural history.
Final Results of the AML12 Trial of the Spanish Cetlam Group in Adults with Acute Myeloid Leukemia (AML) up to the Age of 70 Years: Risk Adapted Post-Remission Allocation Based on Genetic Data and Minimal Residual Disease
Authors: Jorge Sierra, Ana Garrido, Marina Diaz Beya, Montserrat Hoyos, Marisa Calabuig, Susana Vives, Montserrat Arnan Sangerman, Maria Paz Queipo De Llano, Olga Salamero, Ferran Vall-Llovera, Alex Bataller, Francisca Guijarro, Lourdes Escoda, Antonio Garcia-Guiñon, Brayan Merchan, Xavier Ortin, Isabel Sanchez Ortega, Marta Pratcorona, Joan Bargay, Antonia Sampol, Josep Nomdedeu, David Gallardo, Josep-Maria Ribera, Mar Tormo, Jordi Esteve, Salut Brunet
Journal: Blood (2019)
Association of Anticholinergic Drug Exposure With Increased Occurrence of Dementia
Authors: Ronald H. Farkas, Lawrence G. Miller
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
Characteristics of E-cigarette, or Vaping, Products Used by Patients with Associated Lung Injury and Products Seized by Law Enforcement — Minnesota, 2018 and 2019
Authors: Joanne Taylor, Terra Wiens, Jason Peterson, Stefan Saravia, Mark Lunda, Kaila Hanson, Matt Wogen, Paige D’Heilly, Jamie Margetta, Maria Bye, Cory Cole, Erica Mumm, Lauren Schwerzler, Roon Makhtal, Richard Danila, Ruth Lynfield, Stacy Holzbauer, Benjamin C. Blount, Mateusz P. Karwowski, Maria Morel-Espinosa, Liza Valentin-Blasini
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

During August 9-October 31, 2019, 96 patients were classified as having e-cigarette, or vaping, product use-associated lung injury (EVALI) by the Minnesota Department of Health (MDH); other patients are being investigated for case classification and exposures. Among 58 patients interviewed, 53 (91%) reported obtaining tetrahydrocannabinol (THC)-containing products from informal sources such as friends, family members, or in-person or online dealers. Using gas chromatography-mass spectrometry (GCMS), the MDH Public Health Laboratory (PHL) analyzed 46 THC-containing e-cigarette, or vaping, products obtained from 12 EVALI patients for various potential toxicants, including vitamin E acetate, which has recently been detected in some THC-containing products and in samples of lung fluid from EVALI patients (1-4). To explore whether vitamin E acetate is a recently added component in THC-containing products, MDH tested ten products seized by law enforcement in 2018, before the EVALI outbreak, and 20 products seized in 2019, during the outbreak. Twenty-four products obtained from 11 EVALI patients from 2019 contained vitamin E acetate. Among the seized products tested by MDH, none seized in 2018 contained vitamin E acetate, although all tested THC-containing products seized in 2019 tested positive for vitamin E acetate. These chemical analyses of products obtained from EVALI patients and of products intended for the illicit market both before and during the outbreak support a potential role for vitamin E acetate in the EVALI outbreak; however, the number of products tested was small, and further research is needed to establish a causal link between exposure to inhaled vitamin E acetate and EVALI. Collaboration between public health jurisdictions and law enforcement to characterize THC-containing products circulating before the recognition of the EVALI outbreak and during the outbreak might provide valuable information about a dynamic market. These Minnesota findings highlight concerns about e-cigarette, or vaping, products that contain THC acquired from informal sources. Because local supply chains and policy environments vary, CDC continues to recommend not using e-cigarette, or vaping, products that contain THC or any e-cigarette, or vaping, products obtained from informal sources. E-cigarette, or vaping, products should never be used by youths, young adults, or pregnant women.* Until the relationship between inhaled vitamin E acetate and lung health is better characterized, vitamin E acetate should not be added to e-cigarette, or vaping, products.
Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018
Authors: Anass Abbad, Ranawaka APM Perera, Latifa Anga, Abdellah Faouzi, Nhu Nguyen Tran Minh, Sk Md Mamunur Rahman Malik, Nadia Iounes, Abderrahmane Maaroufi, Maria D Van Kerkhove, Malik Peiris, Jalal Nourlil
Journal: Eurosurveillance (2019)

BackgroundMiddle East respiratory syndrome coronavirus (MERS-CoV) remains a major concern for global public health. Dromedaries are the source of human zoonotic infection. MERS-CoV is enzootic among dromedaries on the Arabian Peninsula, the Middle East and in Africa. Over 70% of infected dromedaries are found in Africa. However, all known zoonotic cases of MERS have occurred in the Arabian Peninsula with none being reported in Africa.AimWe aimed to investigate serological evidence of MERS-CoV infection in humans living in camel-herding areas in Morocco to provide insights on whether zoonotic transmission is taking place.MethodsWe carried out a cross sectional seroprevalence study from November 2017 through January 2018. We adapted a generic World Health Organization MERS-CoV questionnaire and protocol to assess demographic and risk factors of infection among a presumed high-risk population. ELISA, MERS-CoV spike pseudoparticle neutralisation tests (ppNT) and plaque neutralisation tests (PRNT) were used to assess MERS-CoV seropositivity.ResultsSerum samples were collected from camel slaughterhouse workers (n = 137), camel herders (n = 156) and individuals of the general population without occupational contact with camels but living in camel herding areas (n = 186). MERS-CoV neutralising antibodies with ≥ 90% reduction of plaque numbers were detected in two (1.5%) slaughterhouse workers, none of the camel herders and one individual from the general population (0.5%).ConclusionsThis study provides evidence of zoonotic transmission of MERS-CoV in Morocco in people who have direct or indirect exposure to dromedary camels.
Brief Pembrolizumab(PEM) Monotherapy Results in Complete and Near Complete Responses in the Majority of Untreated Patients with Classical Hodgkin Lymphoma (cHL): A Multicenter Phase 2 PET-Adapted Study of Sequential PEM and AVD
Authors: Pamela Allen, Hatice Savas, Andrew M. Evens, Barbara Pro, Reem Karmali, Brett Alan Palmer, Eric Mou, Jeffrey Bearden, Denise M Scholtens, Gary Dillehay, Leo I. Gordon, Jane N. Winter
Journal: Blood (2019)
Understanding barriers to oral medication adherence in adults with acute myeloid leukemia (AML).
Authors: Ashley Leak Bryant, Ya-Ning Chan, Jaime Richardson, Matthew Charles Foster, Debra Wujcik
Journal: Journal of Clinical Oncology (2019)

106 Background: AML is a disease of older adults (median age 67 years). Although standard AML treatment is intravenous (IV) chemotherapy, availability of oral anti-cancer medications has increased , providing benefits and risks to patients. Patients prefer their convenience, absence of IV infusions, potential for fewer clinic visits, and increased subjective feeling of control over their disease. Poor adherence can increase toxicity risk and compromise treatment effectiveness. We aim to identify barriers to adherence to oral medications in patients with AML and proposed solutions for improvements. Methods: Following IRB approval, patients with AML and their caregivers were recruited to participate in focus groups. An experienced moderator conducted the groups using an interview guide developed by AML experts. Participants received gift cards for their participation. Sessions were digitally recorded, transcribed verbatim, and analyzed for thematic content using Dedoose qualitative software. Results: 11 patients (5 &lt;65 years; 6 &gt;65 years) and 4 caregivers participated in sessions lasting 60-75 minutes. Three central themes emerged: medication adherence challenges, managing an oral adherence plan, and strategies to improve oral adherence. Adherence challenges: number and size of pills, different directions, cost, availability, and side effects. An adherence plan was recommended: written schedules, take medications around meals, and use of pillboxes and alarms. Main sources of information: health care team and bottle directions. Recommendations for providing adherence assistance included better instructions, assistance with scheduling, making pills smaller, and consistency in packaging. Conclusions: Patients are an important source of insight into barriers and solutions to oral medication adherence. These responses were used to develop a survey to be administered to 100 patients with AML. Results will inform development of an intervention to improve oral medication adherence in the AML population.
Anti-CD20 Therapy Reliance on Antibody-Dependent Cellular Phagocytosis Affects Combination Drug Choice
Authors: Charles C. Chu, Jonathan J. Pinney, Karl R. VanDerMeid, Raquel Izumi, Veerendra Munugalavadla, Paul M. Barr, Michael Rusty Elliott, Clive S Zent
Journal: Blood (2019)
Which Drug Prices Should Medicare Negotiate? A “Too Little” or “Too Late” Approach
Authors: Peter B. Bach
Journal: New England Journal of Medicine (2019)

Interview with Dr. Jonathan Oberlander on legislation aimed at reducing spending on prescription drugs. (08:34)Download By negotiating prices only for drugs that have too little evidence to support full approval or are too late in their life cycle to justify continued high prices, Medicare could both deliver substantial savings and preserve the incentive framework for innovation.
A Cell Membrane‐Targeting Self‐Delivery Chimeric Peptide for Enhanced Photodynamic Therapy and In Situ Therapeutic Feedback
Authors: Wen Ma, Sui‐Nan Sha, Pei‐Ling Chen, Meng Yu, Jian‐Jun Chen, Chao‐Bo Huang, Bin Yu, Yun Liu, Li‐Han Liu, Zhi‐Qiang Yu
Journal: Advanced Healthcare Materials (2019)

Abstract Nowadays, cell membrane‐targeted therapy, which owns high antitumor efficacy by avoiding cell barriers, has received great attention. Here, a cell membrane‐targeted self‐delivery theranostic chimeric peptide CMP‐PpIX is designed for simultaneously targeted photodynamic therapy (PDT) of tumor and real‐time therapeutic feedback. Self‐assembled CMP‐PpIX nanoparticles can effectively accumulate in tumor by enhanced permeability and retention effect without additional vector. And this chimeric peptide CMP‐PpIX has low background fluorescence, which is due to its relatively high intramolecular Förster resonance energy transfer (FRET) quenching efficiency between 5(6)‐carboxyfluorescein (FAM) and 4‐(dimethylaminoazo)‐benzene‐4‐carboxylic acid (Dabcyl). More importantly, CMP‐PpIX can be anchored on the tumor cell membrane for more than 8 h. Under irradiation, reactive oxygen species produced by CMP‐PpIX directly damage cell membrane and rapidly induce apoptosis, which significantly improve the efficacy of PDT in vitro and in vivo. Then, peptide sequence Asp‐Glu‐Val‐Asp (DEVD) is subsequently cleaved by activated caspase‐3 and activated caspase‐7, which separates the FAM and Dabcyl and terminates the FRET process. Therefore, fluorescence of FAM is recovered to monitor the expression of activated caspase‐3 in vitro and in vivo to feedback real‐time PDT therapeutic efficacy. In general, a novel cell membrane‐targeted self‐delivery theranostic chimeric peptide offers new promise for effective imaging‐guided PDT.
Melatonin inhibits inflammasome-associated activation of endothelium and macrophages attenuating pulmonary arterial hypertension
Authors: Jingyuan Zhang, Xiaohui Lu, Mei Liu, Hanlu Fan, Han Zheng, Shanshan Zhang, Nafis Rahman, Sławomir Wołczyński, Adam Kretowski, Xiangdong Li
Journal: Cardiovascular Research (2019)

Abstract Aims Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome associated with pulmonary/systemic inflammation. Melatonin relieves PAH, but the molecular mode of action remains unclear. Here, we investigated the role of melatonin in normalizing vascular homeostasis. Methods and results Light-time mean serum melatonin concentration was lower in patients with PAH than in normal controls [11.06 ± 3.44 (7.13–15.6) vs. 14.55 ± 1.28 (8.0–19.4) pg/mL], which was negatively correlated with increased serum levels of interleukin-1β (IL-1β) in patients with PAH. We showed that inflammasomes were activated in the PAH mice model and that melatonin attenuated IL-1β secretion. On one hand, melatonin reduced the number of macrophages in lung by inhibiting the endothelial chemokines and adhesion factors. Moreover, use of Il1r−/− mice, Caspase1/11−/− mice, and melatonin-treated mice revealed that melatonin reduced hypoxia-induced vascular endothelial leakage in the lung. On the other hand, we verified that melatonin reduced the formation of inflammasome multiprotein complexes by modulating calcium ions in macrophages using a live cell station, and melatonin decreased inositol triphosphate and increased cAMP. Furthermore, knockdown of melatonin membrane receptors blocked melatonin function, and a melatonin membrane receptors agonist inactivated inflammasomes in macrophages. Conclusion Melatonin attenuated inflammasome-associated vascular disorders by directly improving endothelial leakage and decreasing the formation of inflammasome multiprotein complexes in macrophages. Taken together, our data provide a theoretical basis for applying melatonin clinically, and inflammasomes may be a possible target of PAH treatment.
Comprehensive geriatric assessment in lung cancer and hematologic malignancy.
Authors: Zachary Luke Farmer, Anthony James Caprio, Raghava Reddy Induru, Armida Parala-Metz, Markecia Kanese Cooper, Joanna Edeker Lankford, Tiffany Gabrielle Kneuss, Thomas Gregory Knight, Daniel Ernest Haggstrom
Journal: Journal of Clinical Oncology (2019)

122 Background: The incidence of cancer in patients older than 65 is nearly tenfold higher than in their younger counterparts. Comprehensive geriatric assessment (CGA) is recommended for cancer patients &gt; 65 years, as it can more reliably assess underlying function and predict tolerance to anticancer therapy. We reviewed data for patients with lung cancer and hematologic malignancies who completed comprehensive geriatric assessment by the Senior Oncology Section within the Levine Cancer Institute. Methods: From 2015 to 2019 Levine Cancer Institute (LCI) providers performed 96 CGAs in lung cancer patients and 58 in patients with hematologic malignancy, many of the latter being evaluated for bone marrow transplantation. Data was incorporated into an LCI Senior Oncology Clinic Database using the REDCap secure web application, allowing both quantitative and qualitative data analysis. Results: Median ages were 80 in lung cancer and 67 in hematologic malignancy. The lung cancer patients had a slower gait than patients with hematologic malignancy (0.8 m/s versus 1.3 m/s). Lung cancer patients also had a longer median timed up and go (TUG) test of 13 seconds, versus 8 seconds in hematologic malignancy. Considerably more lung cancer patients had experienced a fall within the preceding six months (32 (33%) versus 9 (16%)). The median Cumulative Illness Rating Scale-Geriatric (CIRS-G) total score was significantly higher in lung than in hematologic malignancy (14 versus 8), indicating a higher degree of comorbid illness. Cognitive functioning was comparable between the two groups, with median Montreal Cognitive Assessment (MoCA) scores of 25 in lung and 26 in hematologic malignancy. Conclusions: Lung cancer patients undergoing CGA had more comorbid illnesses, slower gait speed and timed up and go, and more falls in the preceding 6 months than hematologic malignancy patients. Overall cognitive functioning was not significantly different between the two groups. These findings highlight the importance of comprehensive geriatric assessment in elderly lung cancer patients. [Table: see text]
PSMB10, the last immunoproteasome gene missing for PRAAS
Authors: Guillaume Sarrabay, Déborah Méchin, Aicha Salhi, Guilaine Boursier, Cécile Rittore, Yanick Crow, Gillian Rice, Tu-Anh Tran, Renaud Cezar, Darragh Duffy, Vincent Bondet, Lakhdar Boudhane, Christophe Broca, Benjamin P. Kant, Mariëlle VanGijn, Sylvie Grandemange, Eric Richard, Florence Apparailly, Isabelle Touitou
Journal: Journal of Allergy and Clinical Immunology (2019)
Efficacy and safety of first-line durvalumab (D) ± tremelimumab (T) vs chemotherapy (CT) in Asian patients with metastatic NSCLC: Results from MYSTIC
Authors: B.C. Cho, K.H. Lee, M.-J. Ahn, S. Lucien Geater, T.V. Ngoc, C.-C. Wang, E.K. Cho, J.S. Lee, V. Sriuranpong, Q. Bui, S. Clarke, S. Kuyama, K. Nakagawa, F. Liu, D. Clemett, U. Scheuring, S. Peters, N. Rizvi
Journal: Annals of Oncology (2019)