tbuckley/cabot-search huggingface dataset:
ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests
Authors: Allan L. Coates, Jack Wanger, Donald W. Cockcroft, Bruce H. Culver, Kai-Håkon Carlsen, Zuzana Diamant, Gail Gauvreau, Graham L. Hall, Teal S. Hallstrand, Ildiko Horvath, Frans H.C. de Jongh, Guy Joos, David A. Kaminsky, Beth L. Laube, Joerg D. Leuppi, Peter J. Sterk
Journal: European Respiratory Journal (2017)

This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC20) causing a 20% fall in forced expiratory volume in 1 s (FEV1)), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV1 (provocative dose (PD20)). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test.
Erratum: Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up
Authors: R A Larson, A Hochhaus, T P Hughes, R E Clark, G Etienne, D-W Kim, I W Flinn, M Kurokawa, B Moiraghi, R Yu, R E Blakesley, N J Gallagher, G Saglio, H M Kantarjian
Journal: Leukemia (2012)
Post-operative radiation therapy in adenoid cystic carcinoma: A SEER analysis.
Authors: Prashant Joshi, Mark E Smolkin, Patrick Michael Dillon
Journal: Journal of Clinical Oncology (2015)

e17000 Background: Adenoid Cystic Carcinoma (ACC) is a rare malignancy affecting the major and minor salivary glands and also a number of other glandular tissues. Local management is surgery plus or minus adjuvant radiation (RT). No prospective study of RT for resected ACC has been reported. We hypothesized that RT might improve survival for patients with ACC. Methods: The Surveillance, Epidemiology and End Results Database (SEER) database was queried for ACC cases from 1988-2010. The outcomes were survival and cause specific survival (CSS). A univariate analysis of each outcome by whether RT was received, and several demographic, staging, and treatment related factors was performed using K-M survival curves and log–rank tests. Cox proportional hazards multivariate models were used to model the outcomes versus receipt of RT, age, year of diagnosis, gender, race, site, and stage, in addition to the interaction terms between RT and other factors, except for site. Hazard ratios and 95% CI were produced for contrasts of interest. Local control rate could not be adequately assessed. Results: The 10-yr CSS for localized disease was 90% (95% CI: (87%,92%)) for no radiation versus 89% (95% CI: (86%,92%)) for RT, indicating no survival difference. In a multivariate model, there was an increased risk of CS death associated with RT for regional disease (HR 1.50, CI 1.15-1.97, p = 0.003), and a decreased risk for CS death in metastatic disease (HR 0.68, CI 0.47-0.99, p = 0.043). In a multivariate model, there was an increased risk of all-cause death associated with RT for regional disease (HR 1.24, CI 1.01-1.53, p = 0.044), and a trend for decreased risk of death associated with RT for metastatic disease (HR 0.74, CI 0.53-1.03, p = 0.073). Conclusions: There is no evidence of a survival benefit associated with adjuvant RT for adequately resected local ACC in this analysis of the SEER database. A worsened survival for regional ACC suggests a selection bias toward use of RT in higher risk patients. Prospective studies of adjuvant RT in ACC are needed.
Abstract 72: Hydrogen Sulfide Prevents Myocardial Hypertrophy in a Klf5-dependent Manner
Authors: Guoliang Meng, Liping Xie, Yong Ji
Journal: Circulation Research (2015)

Rationale: H 2 S is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel-like transcription factor (KLF) exerts diverse functions in the cardiovascular system. Objectives: The aim of present study was to investigate the effect of hydrogen sulfide (H 2 S) on myocardial hypertrophy. Methods and results: Myocardial samples of 22 patients with left ventricle hypertrophy were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats (SHR) and neonatal rat cardiomyocytes were studied for functional and signaling response to GYY4137, a H 2 S-releasing compound. Expression of cystathionine -lyase (CSE), a main enzyme for H 2 S generation in human heart, decreased in human hypertrophic myocardium, while KLF5 expression increased. In SHR treated with GYY4137 for 4 weeks, myocardial hypertrophy was inhibited as evidenced by improvement in cardiac structural parameters, heart mass index, size of cardiac myocytes and expression of atrial natriuretic peptide (ANP). Levels of oxidative stress and phosphorylation of mitogen-activated protein kinases were also decreased after H 2 S treatment. H 2 S diminished expression of the KLF5 in myocardium of SHR and in neonatal rat cardiomyocytes rendered hypertrophy by angiotensin II (Ang II). H 2 S also inhibited ANP promoter activity and ANP expression in Ang II-induced neonatal rat cardiomyocyte hypertrophy, and these effects were suppressed by KLF5 knockdown. KLF5 promoter activity was increased by Ang II stimulation, and this was reversed by H 2 S. H 2 S also decreased activity of specificity protein-1 (SP-1) binding to the KLF5 promoter and attenuated KLF5 nuclear translocation by Ang II stimulation. Conclusion: H 2 S attenuated myocardial hypertrophy, which might be related to inhibiting oxidative stress and decreasing ANP transcription activity in a KLF5-dependent manner.
Echocardiographic assessment of left ventricular remodeling: Are left ventricular diameters suitable tools? (Journal of the American College of Cardiology (1997) 30 (1534-1541))
Authors: K. S. Dujardin, M. Enriquez-Sarano, A. Rossi, K. R. Bailey, J. B. Seward
Journal: Journal of the American College of Cardiology (1998)
The “Tricky Business” of Identifying Mechanisms of Resistance to Anti–PD-1
Authors: James S. Wilmott, Helen Rizos, Richard A. Scolyer, Georgina V. Long
Journal: Clinical Cancer Research (2017)

Resistance to immune checkpoint inhibitors can vary between patients and among metastases. Understanding the genomic, transcriptomic, and microenvironmental factors that contribute to this variability will reveal the mechanisms that tumors utilize to evade the therapeutic effects of checkpoint inhibitor immunotherapies and will enable us to develop strategies to overcome them. Clin Cancer Res; 23(12); 2921-3. ©2017 AACRSee related article by Ascierto et al., p. 3168.
Fgf21 is required for cardiac remodeling in pregnancy
Authors: Ibon Redondo-Angulo, Aleksandra Mas-Stachurska, Marta Sitges, Francisco José Tinahones, Marta Giralt, Francesc Villarroya, Anna Planavila
Journal: Cardiovascular Research (2017)

Fibroblast growth factor-21 (Fgf21) is an endocrine factor that contributes to many physiological and pathological processes, mainly via its action as a metabolic regulator. Recent studies have shown that Fgf21 plays an important role in cardiac tissue. Pregnancy offers a physiological model of adaptive and reversible heart enlargement, but the molecular mechanisms underlying this cardiac hypertrophy are poorly understood. Therefore, the aim was to analyze the role of Fgf21 during late pregnancy, and assess the physiological relevance of Fgf21 for cardiac tissue during this process.Female mice and rats at day 18 of gestation and pregnant women in their third trimester were used as models of late pregnancy, and our results revealed that their plasma levels of Fgf21 were significantly increased relative to non-pregnant controls. Pregnant wild-type (wt) mice exhibited a PPARα (peroxisome proliferator-activated receptor-α)-dependent enhancement of Fgf21 expression in the liver and heart. Moreover, pregnancy altered the levels of Fgf21 receptor-1 (FGFR1) and β-klotho, and activated intracellular Fgf21 signaling in the heart. Fgf21-/- mice did not develop the pregnancy-induced cardiac remodeling seen in wt mice. Furthermore, the hearts of Fgf21-/- mice exhibited reductions in their fatty acid oxidation levels, which may compromise cardiac function during pregnancy.During pregnancy, both systemic and cardiac-produced Fgf21 act on the heart, leading to the normal physiological cardiac changes that are associated with pregnancy. Thus, Fgf21 acts as an endocrine/autocrine factor required for cardiac remodeling response to gestation.
Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease
Authors: Yi-Bin Chen, Miguel-Angel Perales, Shuli Li, Maria Kempner, Carol Reynolds, Jami Brown, Yvonne A. Efebera, Steven M. Devine, Areej El-Jawahri, Steven L. McAfee, Thomas R. Spitzer, Robert J. Soiffer, Jerome Ritz, Corey Cutler
Journal: Blood (2017)
Effects of Vitamin D Supplementation on Insulin Sensitivity and Insulin Secretion in Subjects With Type 2 Diabetes and Vitamin D Deficiency: A Randomized Controlled Trial
Authors: Hanne L. Gulseth, Cecilie Wium, Kristin Angel, Erik F. Eriksen, Kåre I. Birkeland
Journal: Diabetes Care (2017)

OBJECTIVE In observational studies, low vitamin D levels are associated with type 2 diabetes (T2D), impaired glucose metabolism, insulin sensitivity, and insulin secretion. We evaluated the efficacy of vitamin D supplementation on insulin sensitivity and insulin secretion in subjects with T2D and low vitamin D (25-hydroxyvitamin D [25(OH)D] &amp;lt;50 nmol/L). RESEARCH DESIGN AND METHODS Sixty-two men and women with T2D and vitamin D deficiency participated in a 6-month randomized, double-blind, placebo-controlled trial. Participants received a single dose of 400,000 IU oral vitamin D3 or placebo, and the vitamin D group received an additional 200,000 IU D3 if serum 25(OH)D was &amp;lt;100 nmol/L after 4 weeks. Primary end points were total Rd by euglycemic clamp with assessment of endogenous glucose production and first-phase insulin secretion by intravenous glucose tolerance test. RESULTS In the vitamin D group, the mean ± SD baseline serum 25(OH)D of 38.0 ± 12.6 nmol/L increased to 96.9 ± 18.3 nmol/L after 4 weeks, 73.2 ± 13.7 nmol/L after 3 months, and 53.7 ± 9.2 nmol/L after 6 months. The total exposure to 25(OH)D during 6 months (area under the curve) was 1,870 ± 192 and 1,090 ± 377 nmol/L per week in the vitamin D and placebo groups, respectively (P &amp;lt; 0.001). Insulin sensitivity, endogenous glucose production, and glycemic control did not differ between or within groups after treatment (P = 0.52). First-phase insulin secretion did not change significantly after treatment (P = 0.10). CONCLUSIONS Replenishment with a large dose of vitamin D3 to patients with T2D and vitamin D deficiency did not change insulin sensitivity or insulin secretion. These findings do not support such use of therapeutic vitamin D3 supplementation to improve glucose homeostasis in patients with T2D.
Advances in the detection of telomerase activity using isothermal amplification
Authors: Xiaojin Zhang, Xiaoding Lou, Fan Xia
Journal: Theranostics (2017)

Telomerase plays a significantly important role in keeping the telomere length of a chromosome. Telomerase overexpresses in nearly all tumor cells, suggesting that telomerase could be not only a promising biomarker but also a potential therapeutic target for cancers. Therefore, numerous efforts focusing on the detection of telomerase activity have been reported from polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assays to PCR-free assays such as isothermal amplification in recent decade. In this review, we highlight the strategies for the detection of telomerase activity using isothermal amplification and discuss some of the challenges in designing future telomerase assays as well.
Circulating miRNAs from imprinted genomic regions are associated with peripheral muscle strength in COPD patients
Authors: Jen Y. Lee, Anna V. Donaldson, Amy Lewis, S. Amanda Natanek, Michael I. Polkey, Paul R. Kemp
Journal: European Respiratory Journal (2017)

Reduced muscle mass and strength are common comorbidities of COPD that lead to a poorer quality of life and are associated with increased mortality. Whilst the presence of disease may be viewed as a ‘necessary’ factor for the loss of muscle mass and strength, disease severity itself is not tightly linked to muscle loss, as some patients with mild disease have a significant loss of muscle mass and strength, whereas others with severe disease appear to maintain a normal muscle mass and strength [1]. These differences in susceptibility to changes in muscle are likely to be caused by the interplay between genetic, epigenetic and environmental factors. Circulating levels of miR-485-3p, a maternally expressed miRNA, are associated with muscle strength in COPD patients <http://ow.ly/Wq51309fQtK> The views expressed in this publication are those of the authors and not necessarily those of the NHS, The National Institute for Health Research or the Department of Health.
3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
Authors: Hasnah Osman, Nor Hashima Idris, Ezatul Ezleen Kamarulzaman, Habibah A. Wahab, Mohd. Zaheen Hassan
Journal: Acta Pharmaceutica Sinica B (2017)

Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a-4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28 µmol/L.
The efficacy of percutaneous vertebroplasty for palliation of pain in vertebral metastases associated with solid malignancies
Authors: B. Lee, I. Franklin, C. Coombes, R. Leonard, P. Gishen, J. Stebbing
Journal: Journal of Clinical Oncology (2009)

e20670 Background: Painful vertebral metastases are a debilitating and common complication of a number of solid malignancies. Percutaneous vertebroplasty appears beneficial for patients with acute compression fractures of multiple aetiologies including myeloma, and osteoporosis. There are few reports on its use in the setting of metastatic solid malignancy. Methods: We identified all individuals who had undergone percutaneous vertebroplasty at our institution since 2004 and focused on those with metastatic solid malignancies. Their clinical characteristics and outcomes were investigated. Results: From 136 cases that underwent percutaneous vertebroplasties, 19 were performed mainly in breast, prostate, lung, and renal cancers. Of these 19 cases, ten patients (53%) were treated for solitary lesions, 3 (16%) were injected at two levels and the remaining 6 cases (31%) underwent cement injection at three levels. The majority of patients (84%) reported short (within 48 hours) and longer term symptomatic improvements. At a median follow up of one year, 6 patients have died. Conclusions: This study illustrates that percutaneous vertebroplasty can be a safe and beneficial palliative procedure for patients with pain related to metastatic vertebral disease. Up to three vertebral levels maybe injected at one sitting with good results. Its use can be successfully combined with other treatment modalities (radiotherapy and chemotherapy). For optimal results its use before radiotherapy has been recommended. Although it does not improve the survival outcome, palliation is a reasonable goal when life expectancy is short. Cost benefits from this procedure will come from reduced analgesic requirements and avoided complications of long-term bed rest, with significant potential savings from reduced in-patient admissions for pain control, home care costs, community nursing, and out-of ours access to clinical services. No significant financial relationships to disclose.
Sub-group of patients at risk of bowel cancer may not need follow-up colonoscopy
Authors: Jacqui Wise
Journal: BMJ (2017)

Most patients with intermediate risk adenomas benefit from surveillance colonoscopy, a large study published in Lancet Oncology has found.1 But the researchers said that a subgroup of patients may not need a follow-up colonoscopy, which could lead to cost savings.

In the UK everyone over 60 is invited to be screened for colorectal cancer. Patients who have surgery to remove any growths in the bowel are then classed as low, intermediate, or high risk. The current UK guideline says that patients with one to two large adenomas (1 cm or larger) or three to four small adenomas …
Wireless capsule endoscopy – A new tool for investigation of suspected gastrointestinal bleeding
Authors: NM Kelly, JSA Collins, RGP Watson, HR Ferguson, E Warwick
Journal: Endoscopy (2005)

Aims: To retrospectively review the use of Wireless Capsule Endoscopy (WCE) following negative colonoscopy and oesphagoduodenoscopy in suspected gastrointestinal bleeding.
Rapid Pathogen Identification in Bacterial Pneumonia Using Real-Time Metagenomics
Authors: Kathryn M. Pendleton, John R. Erb-Downward, Yuwei Bao, William R. Branton, Nicole R. Falkowski, Duane W. Newton, Gary B. Huffnagle, Robert P. Dickson
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Hypertriglyceridemia and Pancreatitis—New Evidence That Less Is More
Authors: Frank A. Lederle, Hanna E. Bloomfield
Journal: JAMA Internal Medicine (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 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
DNA methylation signature to identify trastuzumab response in HER2 breast cancer models
Authors: S. Palomeras, Á Díaz Lagares, A. Blancafort, A. Sarrats, A.B. Crujeiras Martinez, J. Sandoval, M. Rabionet, A.L. Welm, M. Esteller, T. Puig
Journal: Annals of Oncology (2017)
Brown-adipose-tissue macrophages control tissue innervation and homeostatic energy expenditure
Authors: Yochai Wolf, Sigalit Boura-Halfon, Nina Cortese, Zhana Haimon, Hadas Sar Shalom, Yael Kuperman, Vyacheslav Kalchenko, Alexander Brandis, Eyal David, Yifat Segal-Hayoun, Louise Chappell-Maor, Avraham Yaron, Steffen Jung
Journal: Nature Immunology (2017)
CD177<sup>+</sup>neutrophils as functionally activated neutrophils negatively regulate IBD
Authors: Guangxi Zhou, Lin Yu, Leilei Fang, Wenjing Yang, Tianming Yu, Yinglei Miao, Minhu Chen, Kaichun Wu, Feidi Chen, Yingzi Cong, Zhanju Liu
Journal: Gut (2017)

Background Neutrophils are accumulated in inflamed mucosa of IBD and play an important role in the pathogenesis. CD177 is expressed in neutrophils specifically and upregulated during inflammation. However, the role of CD177 + neutrophils in pathogenesis of IBD remains elusive. Materials and methods Expression of CD177 was analysed in peripheral blood and intestinal mucosa from patients with IBD using quantitative RT-PCR, flow cytometry and immunohistochemistry. CD177 + and CD177 − neutrophils were isolated to determine gene differences by RNA sequencing. Colitis was established in CD177 −/− and wild-type mice in response to dextran sulfate sodium (DSS) insults to determine the role of CD177 + neutrophils in IBD. Results CD177 + neutrophils were markedly increased in peripheral blood and inflamed mucosa from patients with active IBD compared with healthy controls. RNA sequencing revealed that differential gene expression between CD177 + and CD177 − neutrophils from patients with IBD was associated with response to bacterial defence, hydrogen peroxide and reactive oxygen species (ROS). CD177 + neutrophils produced lower levels of proinflammatory cytokines (ie, interferon-γ, interleukin (IL)-6, IL-17A), but higher levels of IL-22 and transforming growth factor-β, and exhibited increased bactericidal activities (ie, ROS, antimicrobial peptides, neutrophil extracellular trap) compared with CD177 − subset. CD177 −/− mice developed more severe colitis on DSS insults compared with wild-type mice. Moreover, CD177 deficiency led to compromised intestinal barrier and impaired antibacterial immunity through decreased production of IL-22 by CD177 − neutrophils. Conclusions CD177 + neutrophils represent functionally activated population and play a protective role in IBD through increased bactericidal activity and IL-22 production. Targeting CD177 + neutrophils may be beneficial for treatment of IBD.
Permanent GME Funding for Teaching Health Centers
Authors: Shayla N. M. Durfey, Paul George, Eli Y. Adashi
Journal: JAMA (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 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
A strategy for bypassing the blood-brain barrier: Facial intradermal brain-targeted delivery via the trigeminal nerve
Authors: Xi-Chong Yu, Jing-Jing Yang, Bing-Hui Jin, He-Lin Xu, Hong-Yu Zhang, Jian Xiao, Cui-Tao Lu, Ying-Zheng Zhao, Wei Yang
Journal: Journal of Controlled Release (2017)