tbuckley/cabot-search huggingface dataset:
Overall Survival and Causes of Death in Neurodegeneration—An Overlooked and Underreported Theme—Reply
Authors: Rodolfo Savica, Michelle M. Mielke
Journal: JAMA Neurology (2017)

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 Neurology 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 Neurology journal
Effect of pirfenidone on cough in patients with idiopathic pulmonary fibrosis
Authors: Mirjam J.G. van Manen, Surinder S. Birring, Carlo Vancheri, Virginia Vindigni, Elisabetta Renzoni, Anne-Marie Russell, Monique Wapenaar, Vincent Cottin, Marlies S. Wijsenbeek
Journal: European Respiratory Journal (2017)

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. In patients with IPF, cough is one of the most disabling symptoms and is an independent predictor of disease progression [1–3]. Cough in IPF is often non-responsive to antitussive therapy [4], and studies on cough are scarce and have unfortunately not yet resulted in effective treatments. Several observations suggest that pirfenidone, an anti-fibrotic drug, might decrease cough [5, 6]. We aimed to measure objectively the effect of pirfenidone on cough in patients with IPF and substantial cough. In addition, we assessed the effect of pirfenidone on subjective cough and quality of life (QoL) measures. In patients with IPF, pirfenidone reduces objective 24-h cough counts and improves subjective measures of cough <http://ow.ly/iiGu30f7Pea> The authors thank Marion Durand (Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France), Marjolein Gerrits (Erasmus University Medical Center, Rotterdam, The Netherlands) and Claire Wood (King's College London, London, UK) for clinical research assistance, and Daan Nieboer (Erasmus University Medical Center) for statistical support. Author contributions: S.S. Birring, C. Vancheri, V. Cottin and M.S. Wijsenbeek designed the study. M.J.G. van Manen, C. Vancheri, V. Vindigni, E. Renzoni, A. Russell, V. Cottin and M.S. Wijsenbeek were involved in data collection. M.J.G. van Manen, S.S. Birring, M. Wapenaar and M.S. Wijsenbeek performed data analyses. M.J.G. van Manen and M.S. Wijsenbeek drafted the manuscript. All authors interpreted the data and worked collaboratively to review and prepare the final article.
Chronic Obstructive Pulmonary Disease
Authors: Antonello Punturieri, Thomas L. Croxton, Gail G. Weinmann, James P. Kiley
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The past decade has witnessed great progress in chronic obstructive pulmonary disease (COPD) research.New drugs have been developed and tested, indications for lung volume reduction surgery (LVRS) have been determined, and a growing base of scientific evidence now documents the efficacy of various therapies for symptoms and exacerbations.This advance in knowledge shatters the old conception of COPD as a hopelessly untreatable condition (1-4).It is clear that many patients with COPD can benefit from aggressive management, with a decrease in the frequency of hospitalizations and improvements in quality of life and survival.In addition, basic and clinical scientists have now identified cells, mechanisms, and molecules that appear to play key roles in disease pathogenesis.Additional novel treatments are on the horizon.The good news about COPD is getting out as many organizations are working effectively to increase awareness of the disease (5).Despite advances in care, the COPD epidemic persists, causing more than 120,000 deaths per year in the United States alone.COPD's position as the fourth leading cause of death in the United States is ominous and the probability of the number of cases rising even further is disturbing.Population-based surveys show that as many as 24 million people in the United States have airflow limitation consistent with COPD and that half or more of these cases have not yet been diagnosed (6).Despite the availability of effective treatments for COPD, no existing therapy halts or reverses the progressive and accelerated decline in lung function that is characteristic of this condition.We are far from having a cure for COPD, and in fact, the most basic questions about this disease remain unanswered:d Why do only a minority of smokers develop clinically significant COPD?d Why is there great heterogeneity in the presentation of COPD?d Which pathogenetic pathways are critical, and how can they be modulated therapeutically?d Why does the disease continue to progress even after smoking cessation?d How can the lung injury that characterizes COPD be reversed?
Heart in Hand
Authors: Erica C. Nakajima
Journal: Annals of Internal Medicine (2017)

Ad Libitum17 October 2017Heart in HandErica C. NakajimaErica C. NakajimaFrom Nashville, Tennessee.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-1617 Audio Reading - “Heart in Hand” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Heart in Hand," by E.C. Nakajima. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail When you were three weeks old,a mere comma in the womb,your heart was a simple tube.Shivering with its first beats,and bathed in evolution's finest signals,it folded.Each portion rearranged,the bottom rose to the top.Cells from elsewhere in your bodymade the journey to your heart,thickening its walls.From cushions of cardiac tissue,your septa sprouted and fused.Radiating from this center,lungs blossomed.Limb buds became limbs.Nerves carriedthe promise of sensation.The most exquisite thing I have ever heldwas such a heart,but full grown, then spent.Ambitions achieved or relinquished.It seemed proud of ... Author, Article, and Disclosure InformationAffiliations: From Nashville, Tennessee.Current Author Address: Erica C. Nakajima, MD, Vanderbilt University Medical Center, 1211 Medical Center Drive, Department of Internal Medicine, D-3100 Medical Center North, Nashville, TN 37232; e-mail, erica.c.[email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Heart in Hand” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Heart in Hand," by E.C. Nakajima. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 17 October 2017Volume 167, Issue 8Page: 601KeywordsCellsHeartLungsMusclesMuscular dystrophiesNervesUterus ePublished: 17 October 2017 Issue Published: 17 October 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
TCT-361 Early Experience with the Symetis bioprosthesis in real world patients: The Milan Registry
Authors: Paolo Pagnotta, Cristina Panico, Francesco Giannini, Luca Baldetti, Francesco Cannata, Matteo Montorfano, Mauro Chiarito, Alaide Chieffo, Azeem Latib, Bernhard Reimers, Antonio Colombo
Journal: Journal of the American College of Cardiology (2017)
TCT-617 Implantation of commercially available transcatheter heart valves (THV) for treatment of native calcific mitral stenosis: Results from the First German THV Mitral Stenosis Registry
Authors: Johannes Schirmer, David Michael Holzhey, Jan-Malte Sinning, Holger Schroefel, Frank Oertel, Sabine Bleiziffer, Axel Unbehaun, Alexander Lauten, Christian Frerker, Stefan Blankenberg, Hermann Reichenspurner, Lenard Conradi, Ulrich Schäfer
Journal: Journal of the American College of Cardiology (2017)
TCT-454 Impact of Underexpansion on IVUS-Derived Wall Shear Stress Patterns with Bioresorbable Scaffolds and Metallic DES: Insights from the ABSORB III Imaging Substudy
Authors: Bill Gogas, Elizabeth Thompson, David Molony, Nikolaos Spilias, Kozo Okada, Yasuhiro Honda, Alessandro Veneziani, Don P. Giddens, Richard Rapoza, Jeffrey J. Popma, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer
Authors: Debra M. Krupke, Dale A. Begley, John P. Sundberg, Joel E. Richardson, Steven B. Neuhauser, Carol J. Bult
Journal: Cancer Research (2017)

Abstract Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67–70. ©2017 AACR.
Abstract 20316: Nitric Oxide Synthase (NOS3) Asp298Glu Polymorphism and Survival in Pulmonary Arterial Hypertension
Authors: Andrew Klein, David Ishizawar, Karen Hanley-Yanez, Dennis M McNamara
Journal: Circulation (2016)

Introduction: For subjects with pulmonary arterial hypertension (PAH), differences in genetic background may influence outcomes and the impact of therapeutic interventions. Nitric oxide (NO) is an ...
Abstract 14303: Chronic Inhibition of Ca2+/Calmodulin-Dependent Protein Kinase II by KN-93 Causes Regression of Cardiac Dysfunction in Rats With isoproterenol-induced Heart Failure
Authors: Che-Ping Cheng, Qun Shao, Heng-Jie Cheng, Michael F Callahan, Tiankai Li
Journal: Circulation (2016)

Background: Recent evidence indicates that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is upregulated in heart failure (HF), contributing to electric, structural and functional remodeling....
TCT-117 Impact of Discharge Location After Transcatheter Aortic Valve Replacement On 1-Year Outcomes In Women: Results From The WIN-TAVI Registry
Authors: Julinda Mehilli, Alaide Chieffo, Anna Sonia Petronio, Jaya Chandrasekhar, Samantha Sartori, Thierry Lefevre, Piera Capranzano, Didier Tchetche, Alessandro Iadanza, Gennaro Sardella, Nicolas Van Mieghem, Nicolas Dumonteil, Chiara Fraccaro, Daniela Trabattoni, Ghada Mikhail, Samin Sharma, Maria-Cruz Ferrer Gracia, Peter Kievit, Usman Baber, Clayton Snyder, Madhav Sharma, Marie-Claude Morice, Roxana Mehran
Journal: Journal of the American College of Cardiology (2017)
Abstract 12164: Inhibition of NOTCH3 Cleavage Effectively Reverses Pulmonary Hypertension in Rat and Mouse Models of Disease
Authors: Jonathan R Gower, Yu Zhang, Martanday Singh, Mikaela Louie, Marie Nyugen, Kirk Peterson, Patricia Thistlethwaite
Journal: Circulation (2016)

Background: NOTCH3 signaling is required for the proliferation of vascular smooth muscle cells. NOTCH3 signaling has been implicated in the development of pulmonary arterial hypertension (PAH) as reflected by increased levels of cleaved NOTCH3 and its downstream effector, HES-5 in small pulmonary artery smooth muscle cells (PASMCS) of PAH patients. Gamma-secretase inhibitor drugs that block NOTCH cleavage are effective in treating pulmonary hypertension (PH) in rodents, but they are associated with toxic side effects. Hypothesis: We hypothesize that a monoclonal antibody that specifically blocks NOTCH3 cleavage will effectively reverse PH in rodent models of disease, with an acceptable safety profile. Methods/Results: A monoclonal antibody specific to rodent and human NOTCH3 (Anti-NOTCH3 Ab) was made and shown to block Jagged-1/Delta-like 4-mediated NOTCH3 cleavage in PASMCs in vitro . We tested Anti-NOTCH3 Ab for its ability to reverse PH in mouse hypoxia and rat Sugen models. After 4 weeks of hypoxia, mice treated with Anti-NOTCH3 Ab for 6 weeks demonstrated normalization of right ventricular systolic pressure (mean 17 mmHg), compared to RVSP in control mice (mean 35mmHg). Treated mice demonstrated reversal of small vessel remodeling and had angiograms consistent with normal vasculature. In the Sugen model, rats treated with Anti-NOTCH3 Ab for 10 weeks showed reversal of established disease. This included normalization of RVSPs (mean 18 mmHg - treated group vs. 70 mmHg - control group), normalization of TAPSE values (mean 3.7 mm - treated group vs. 2.4 mm - control group) and normalization of PAAT values (mean 42 msec - treated group vs. 17 msec - control group). The lungs of Anti-NOTCH3 Ab-treated rats had reversal of small vessel remodeling with loss of medial hypertrophy. Western blot analysis showed significantly decreased cleavage of NOTCH3 in the treated group vs. control group. Anti-NOTCH3 Ab-treated rodents did not manifest clinical side effects and had normal organ histology of brain, liver, kidney, intestine, skin, ovary, and heart. Conclusion: Inhibition of cleavage of NOTCH3 by a monoclonal Anti-NOTCH3 Ab effectively treats PH in mouse hypoxia and rat Sugen models. Anti-NOTCH3 Ab treatment was associated with an acceptable safety profile.
Nanoparticle Delivery of miR-34a Eradicates Long-term-cultured Breast Cancer Stem Cells via Targeting C22ORF28 Directly
Authors: Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P Zhou, Mien-Chie Hung, Xiaoming Xie
Journal: Theranostics (2017)

Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning protocol. Tissue microarray analysis has been used to study 217 cases of clinical breast cancer specimens. Results: Here, we have successfully established four long-term maintenance BCSC that retain their tumor-initiating biological properties. Our analyses of microarray and qRT-PCR explored that miR-34a is the most pronounced microRNA for investigation of BCSC. We establish hTERT promoter-driven VISA delivery of miR-34a (TV-miR-34a) plasmid that can induce high throughput of miR-34a expression in BCSC. TV-miR-34a significantly inhibited the tumor-initiating properties of long-term-cultured BCSC in vitro and reduced the proliferation of BCSC in vivo by an efficient and safe way. TV-miR-34a synergizes with docetaxel, a standard therapy for invasive breast cancer, to act as a BCSC inhibitor. Further mechanistic investigation indicates that TV-miR-34a directly prevents C22ORF28 accumulation, which abrogates clonogenicity and tumor growth and correlates with low miR-34 and high C22ORF28 levels in breast cancer patients. Conclusion: Taken together, we generated four long-term maintenance BCSC derived from either clinical specimens or cell lines, which would be greatly beneficial to the research progress in breast cancer patients. We further developed the non-viral TV-miR-34a plasmid, which has a great potential to be applied as a clinical application for breast cancer therapy.
Wealth-Associated Disparities in Death and Disability in the United States and England
Authors: Lena K. Makaroun, Rebecca T. Brown, L. Grisell Diaz-Ramirez, Cyrus Ahalt, W. John Boscardin, Sean Lang-Brown, Sei Lee
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> Low income has been associated with poor health outcomes. Owing to retirement, wealth may be a better marker of financial resources among older adults. <h3>Objective</h3> To determine the association of wealth with mortality and disability among older adults in the United States and England. <h3>Design, Setting, and Participants</h3> The US Health and Retirement Study (HRS) and English Longitudinal Study of Aging (ELSA) are nationally representative cohorts of community-dwelling older adults. We examined 12 173 participants enrolled in HRS and 7599 enrolled in ELSA in 2002. Analyses were stratified by age (54-64 years vs 66-76 years) because many safety-net programs commence around age 65 years. Participants were followed until 2012 for mortality and disability. <h3>Exposures</h3> Wealth quintile, based on total net worth in 2002. <h3>Main Outcomes and Measures</h3> Mortality and disability, defined as difficulty performing an activity of daily living. <h3>Results</h3> A total of 6233 US respondents and 4325 English respondents aged 54 to 64 years (younger cohort) and 5940 US respondents and 3274 English respondents aged 66 to 76 years (older cohort) were analyzed for the mortality outcome. Slightly over half of respondents were women (HRS: 6570, 54%; ELSA: 3974, 52%). A higher proportion of respondents from HRS were nonwhite compared with ELSA in both the younger (14% vs 3%) and the older (13% vs 3%) age cohorts. We found increased risk of death and disability as wealth decreased. In the United States, participants aged 54 to 64 years in the lowest wealth quintile (Q1) (≤$39 000) had a 17% mortality risk and 48% disability risk over 10 years, whereas in the highest wealth quintile (Q5) (&gt;$560 000) participants had a 5% mortality risk and 15% disability risk (mortality hazard ratio [HR], 3.3; 95% CI, 2.0-5.6;<i>P</i> &lt; .001; disability subhazard ratio [sHR], 4.0; 95% CI, 2.9-5.6;<i>P</i> &lt; .001). In England, participants aged 54 to 64 years in Q1 (≤£34,000) had a 16% mortality risk and 42% disability risk over 10 years, whereas Q5 participants (&gt;£310,550) had a 4% mortality risk and 17% disability risk (mortality HR, 4.4; 95% CI, 2.7-7.0;<i>P</i> &lt; .001; disability sHR, 3.0; 95% CI, 2.1-4.2;<i>P</i> &lt; .001). In 66- to 76-year-old participants, the absolute risks of mortality and disability were higher, but risk gradients across wealth quintiles were similar. When adjusted for sex, age, race, income, and education, HR for mortality and sHR for disability were attenuated but remained statistically significant. <h3>Conclusions and Relevance</h3> Low wealth was associated with death and disability in both the United States and England. This relationship was apparent from age 54 years and continued into later life. Access to health care may not attenuate wealth-associated disparities in older adults.
A young man with severe acute haemolytic anaemia
Authors: Xi Chen, Yongshu He, Yinglei Miao, Zhaoqing Yang, Liwang Cui
Journal: BMJ (2017)

Correspondence to Z Yang zhaoqingy92@hotmail.com

A 19 year old man of Kachin ethnicity presented with fever (39.5°C) and was diagnosed with vivax malaria by microscopy. He was prescribed chloroquine and primaquine and his fever resolved. After 24 hours he experienced two days of passing dark urine, followed by an episode of syncope, and was admitted to hospital. On admission, he weighed 59 kg and was afebrile (36.2°C), his heart rate was 120 beats/min, blood pressure 70/40 mm Hg, and respiratory rate 36 breaths/min. He was moderately jaundiced and his conjunctivae and nail beds were pale. The spleen was palpable at 1.5 cm below the left costal margin. His blood smear was negative for malaria parasites and a beam test was negative.

Tests showed reduced haemoglobin (34 g/L; reference range 110-160), hematocrit (9.2%; 35-50), and red blood cell count (1.1×1012/L; 3.5-5.5×1012). The patient’s urine contained bilirubin and haemoglobin but no red blood cells. Total bilirubin was 71.9 µmol/L (reference range 3.4-17.1), unconjugated bilirubin 52.1 µmol/L (1.7-10.2); urea nitrogen 18.45 mmol/L (1.07-7.14), and creatinine 235.4 µmol/L (44-132). A fluorescent spot test found G6PD deficiency, enabling a diagnosis of acute haemolytic anaemia. Genotyping by a SNaPshot assay1 of G6PD in 11 common G6PD mutations that occur in south-east Asia showed that he carried the G6PD Mahidol variant (487G >A) (fig 1). …
Liquid Biopsies Using Plasma Exosomal Nucleic Acids and Plasma Cell-Free DNA Compared with Clinical Outcomes of Patients with Advanced Cancers
Authors: Lino Möhrmann, Helen J. Huang, David S. Hong, Apostolia M. Tsimberidou, Siqing Fu, Sarina A. Piha-Paul, Vivek Subbiah, Daniel D. Karp, Aung Naing, Anne Krug, Daniel Enderle, Tina Priewasser, Mikkel Noerholm, Erez Eitan, Christine Coticchia, Georg Stoll, Lisa-Marie Jordan, Cathy Eng, E. Scott Kopetz, Johan Skog, Funda Meric-Bernstam, Filip Janku
Journal: Clinical Cancer Research (2017)

Purpose: Blood-based liquid biopsies offer easy access to genomic material for molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates from dying cells. Exosomal nucleic acids (exoNAs) originate from living cells, which can better reflect underlying cancer biology.Experimental Design: Next-generation sequencing (NGS) was used to test exoNA, and droplet digital PCR (ddPCR) and BEAMing PCR were used to test cfDNA for BRAFV600, KRASG12/G13, and EGFRexon19del/L858R mutations in 43 patients with progressing advanced cancers. Results were compared with clinical testing of archival tumor tissue and clinical outcomes.Results: Forty-one patients had BRAF, KRAS, or EGFR mutations in tumor tissue. These mutations were detected by NGS in 95% of plasma exoNA samples, by ddPCR in 92% of cfDNA samples, and by BEAMing in 97% cfDNA samples. NGS of exoNA did not detect any mutations not present in tumor, whereas ddPCR and BEAMing detected one and two such mutations, respectively. Compared with patients with high exoNA mutation allelic frequency (MAF), patients with low MAF had longer median survival (11.8 vs. 5.9 months; P = 0.006) and time to treatment failure (7.4 vs. 2.3 months; P = 0.009). A low amount of exoNA was associated with partial response and stable disease ≥6 months (P = 0.006).Conclusions: NGS of plasma exoNA for common BRAF, KRAS, and EGFR mutations has high sensitivity compared with clinical testing of archival tumor and testing of plasma cfDNA. Low exoNA MAF is an independent prognostic factor for longer survival. Clin Cancer Res; 24(1); 181-8. ©2017 AACR.