tbuckley/cabot-search huggingface dataset:
Nuclear Circulating Tumor Cell Androgen Receptor Variant 7 in Castration-Resistant Prostate Cancer
Authors: Stephen R. Plymate, Adam Sharp, Johann S. de Bono
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Anemia and Iron Deficiency in Heart Failure
Authors: Inder S. Anand, Pankaj Gupta
Journal: Circulation (2018)

Anemia and iron deficiency are important and common comorbidities that often coexist in patients with heart failure. Both conditions, together or independently, are associated with poor clinical status and worse outcomes. Whether anemia and iron deficiency are just markers of heart failure severity or whether they mediate heart failure progression and outcomes and therefore should be treated is not entirely clear. Treatment of anemia in patients with heart failure with erythropoiesis-stimulating agents has been evaluated intensively during the past several years. Unfortunately, these agents did not improve outcomes but were associated with a higher risk of adverse events. Iron deficiency in patients with heart failure can be absolute, when total body iron is decreased, or functional, when total body iron is normal or increased but is inadequate to meet the needs of target tissues because of sequestration in the storage pool. Whereas iron replacement is appropriate in patients with anemia resulting from absolute iron deficiency, it has been unclear whether and how absolute or functional iron deficiency should be treated in nonanemic patients with heart failure. Recently, small studies found that administration of intravenous iron in patients with heart failure and absolute or functional iron deficiency with or without anemia improves symptoms and exercise capacity, but long-term outcomes and safety data are not yet available. In this review, we discuss the causes and pathogenesis of and treatment options for anemia and iron deficiency in patients with heart failure.
Association of Gestational Age at Birth With Symptoms of Attention-Deficit/Hyperactivity Disorder in Children
Authors: Helga Ask, Kristin Gustavson, Eivind Ystrom, Karoline Alexandra Havdahl, Martin Tesli, Ragna Bugge Askeland, Ted Reichborn-Kjennerud
Journal: JAMA Pediatrics (2018)

Preterm birth is associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD); however, it is unclear to what extent this association can be explained by shared genetic and environmental risk factors and whether gestational age at birth is similarly related to inattention and hyperactivity/impulsivity and to the same extent in boys and girls.
Correlation between parameters of volumetric capnography and spirometry during a submaximal exercise protocol on a treadmill in patients with cystic fibrosis and healthy controls
Authors: P.L.F. Parazzi, F.A.L. Marson, M.A.G.O. Ribeiro, C.I.S. Schivinski, J.D. Ribeiro
Journal: Pulmonology (2018)

Spirometry is the most frequently used test to evaluate the progression of lung damage in cystic fibrosis (CF). However, there has been low sensitivity in detecting early lung changes. In this context, our objective was to identify the correlation between parameters of volumetric capnography (VCap) and spirometric parameters during a submaximal treadmill exercise test. A cross-sectional and controlled study which included 64 patients with CF (CFG) and 64 healthy control subjects (CG) was performed. The CFG was from a university hospital and the CG from local schools. All participants underwent spirometry and VCap before, during and after the submaximal treadmill exercise test. The main variable analyzed by VCap was the slope of phase 3 (slope 3), which indicates the [exhaled carbon dioxide] at the end of expiration, and expresses the heterogeneity of gas emptying in pulmonary periphery. The correlation analysis between spirometry and VCap was conducted using the Spearman correlation test, considering α = 0.05. The indices analyzed by VCap showed correlation with parameters of VCap. Slope 3 showed an inverse correlation with forced expiratory volume in the first second of forced vital capacity (FEV1) in both groups and at all moments of the submaximal treadmill exercise test. Forced vital capacity (FVC) and FEV1/FVC ratio showed an inverse correlation with slope 3 only for CFG. Values of slope 3 corrected by the spontaneous tidal volume (VT) and end-tidal carbon dioxide tension (PetCO2) showed results similar to slope 3 analyzed separately. Parameters of VCap such as slope 3, slope 3/VT and slope 3/PetCO2 correlated with sensitive variables of spirometry such as FEV1, FVC and FEV1/FVC ratio. For the evaluated variables, there was consistency in the correlation between the two tests, which may indicate the impact of CF on pulmonary physiology.
Inspiratory muscle training in COPD: can data finally beat emotion?
Authors: Michael I Polkey, Nicolino Ambrosino
Journal: Thorax (2018)

Some concepts in medicine (as perhaps with other aspects of life) are so appealing that their appeal endures in the absence of data. Inspiratory muscle training (IMT) in COPD is arguably one example.

In 1976, Leith and Bradley showed, in a study undertaken in a handful of healthy subjects,1 that IMT could improve maximum inspiratory mouth pressure (PImax). The rationale for IMT in patients with COPD was based on the observations that PImax was reduced in COPD2 and on the data which seemed to show that respiratory muscle fatigue limited exercise in COPD.3 IMT was welcomed by enthusiasts perhaps because it came against a paucity of effective treatments for COPD, and early studies showed that, as with healthy volunteers, IMT could improve performance on tests of inspiratory muscle strength. As elegantly documented in a recent editorial,4 responsible opinion, including the American College of Chest Physicians,5 the American Thoracic Society and European Respiratory Society,6 continued on the one hand to recommend that IMT be included in pulmonary rehabilitation programmes (PRPs) for patients with COPD while on the other hand requesting more studies.

This story, which played over decades, in fact defied data at each stage. First, it was by no means certain that IMT improved inspiratory muscle strength; even Leith and Bradley’s original work1 showed that the type of training undertaken determined which test results improved (ie, …
Virus-Induced Interferon-γ Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity
Authors: Marko Šestan, Sonja Marinović, Inga Kavazović, Đurđica Cekinović, Stephan Wueest, Tamara Turk Wensveen, Ilija Brizić, Stipan Jonjić, Daniel Konrad, Felix M. Wensveen, Bojan Polić
Journal: Immunity (2018)
Drug Points: Arthralgias and omeparzole
Authors: M Beutler, K Hartmann, M Kuhn, J Gartmann
Journal: BMJ (1994)

GARTMANN (Swiss Drug Monitoring Centre, write: We describe five cases of arthralgia associated with ome- prazole.In all cases the patients were treated with 20-40 mg omeprazole daily.A 27 year old woman was given omeprazole for a duodenal ulcer that was unresponsive to ranitidine.After 10 days she developed swelling of her fingers, knees, and ankles, with pruritus and erythema over the metacarpal joints.Treatment was stopped and symptoms disappeared within 10 days.
Abstract 4586: Evaluation of available blood collection tubes for use in stabilizing concentrations of extracellular vesicles / exosomes and associated cell-free RNA
Authors: Nicholas George
Journal: Cancer Research (2018)

Abstract Introduction: Liquid Biopsy has revolutionized the detection and the monitoring of cancer disease states. In addition to the widely utilized circulating cell-free DNA (ccfDNA), cell-free RNAs (cfRNA) and the extracellular vesicles (EV's) / exosomes they are stored in, is drawing significant interest in cancer diagnostics. Analysis of disease-specific EV's / exosomes or cfRNA requires that collected samples maintain draw-time concentrations of these analytes in order to remain relevant. Blood components, such as platelets, red, and white blood cells, are unstable when stored in normal blood collection tubes (BCT's), thus leading to increases of EVs and associated cfRNA concentration. We undertook an analysis of currently available commercial BCT's to determine whether any of these sufficiently stabilize EV / exosome and cfRNA concentration. Materials and Methods: Healthy consenting adult donors were drawn into blood collection tubes per approved protocol. Samples were either processed immediately (Day-0) or allowed to incubate at room temperature for the indicated times. Cleared plasma was isolated and subsequently frozen at -80oC until use. Assay of extracellular vesicle concentration utilized the Nanosight-300 (Malvern Instruments) per manufactures protocol. Isolation of cell-free RNA utilized the Circulating Nucleic Acid Isolation Kit (Qiagen) per manufacturer's protocol with the exception of the lysis step; this was extended from 30 minutes to 60 minutes. Digital PCR (ddPCR) utilized the Bio-Rad workflow (QX200 Droplet Generator and Reader). Conclusion: Stabilization of EV's and cfRNA was assayed for blood samples drawn into a variety of Streck nucleic acid stabilizing BCT's, non-Streck nucleic acid stabilizing BCT's, and a traditional K3EDTA BCT. A majority of the assayed tubes led to time-dependent increases in EV concentration with the most robust increases occurring between Day-3 and Day-7. Time-dependent increases in cfRNA concentration mirrored the increases observed in EV's, and based on ddPCR analysis; the majority of this increase was likely the result of erythrocyte membrane shedding. One type of Streck BCT was found to stabilize both EV and cfRNA concentration as a function of blood storage time. Incorporation of this tube into the Liquid Biopsy workflow will maximize assay target sensitivity by preventing the deleterious effects of excess cfRNA from non-specific release of EV's / exosomes. Citation Format: Nicholas George. Evaluation of available blood collection tubes for use in stabilizing concentrations of extracellular vesicles / exosomes and associated cell-free RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4586.
Abstract 266: Disulfiram overcomes docetaxel resistance in prostate cancer by targeting the neddylation pathway and down-regulation of Skp2 expression
Authors: Liankun Song, Bin Yu, Hong-Min Liu, Xiaolin Zi
Journal: Cancer Research (2018)

Abstract Disulfiram (DSF), an inhibitor of aldehyde dehydrogenase and a dithiocarbamate chelator of copper, has been clinically used for treatment of alcohol dependence for decades. A population-based case control study has suggested that the use of DSF is associated with reduced risk of prostate cancer. In addition, copper is accumulated in prostate cancer and can act synergistically with DSF to inhibit the growth of prostate cancer cells. These accumulating data suggested that DSF is a very promising agent to be repurposed for prostate cancer treatment and prevention. However, the anti-cancer mechanisms of DSF currently remain largely unknown. Here we have shown that DSF treatment decreases the neddylation levels of NEDD8-conjugating enzyme UBE2M and Cullin-1 leading to down-regulation of Skp2 expression in prostate cancer DU145 cells. Further co-immunoprecipitation experiment revealed that DSF disrupted the formation of the defective in Cul neddylation 1 protein (DCN1) and UBE2M complex. DSF synergistically enhanced the growth inhibitory effect of docetaxel on prostate cancer cell lines and overcame the drug resistance. Taken together, these data may provide proof of concept for rationally designed repurpose of DSF to treat docetaxel-resistant prostate cancer by involvement of the neddylation pathway. Citation Format: Liankun Song, Bin Yu, Hong-Min Liu, Xiaolin Zi. Disulfiram overcomes docetaxel resistance in prostate cancer by targeting the neddylation pathway and down-regulation of Skp2 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 266.
A disintegrin and metalloproteinase 15-mediated glycocalyx shedding contributes to vascular leakage during inflammation
Authors: Xiaoyuan Yang, Jamie E Meegan, Melanie Jannaway, Danielle C Coleman, Sarah Y Yuan
Journal: Cardiovascular Research (2018)

Endothelial hyperpermeability exacerbates multiple organ damage during inflammation or infection. The endothelial glycocalyx, a protective matrix covering the luminal surface of endothelial cells (ECs), undergoes enzymatic shedding during inflammation, contributing to barrier hyperpermeability. A disintegrin and metalloproteinase 15 (ADAM15) is a sheddase capable of cleaving the ectodomains of membrane-bound molecules. Herein, we tested whether and how ADAM15 is involved in glycocalyx shedding and vascular leakage during sepsis. Dextran-150kD exclusion assay revealed lipopolysaccharide (LPS) significantly reduced glycocalyx thickness in mouse cremaster microvessels. Consistently, shedding products of glycocalyx constituents, including CD44 ectodomain, were detected with an increased plasma level after cecal ligation and puncture (CLP)-induced sepsis. The direct effects of CD44 ectodomain on endothelial barrier function were evaluated, which revealed CD44 ectodomain dose-dependently reduced transendothelial electrical resistance (TER) and caused cell–cell adherens junction disorganization. Furthermore, we examined the role of ADAM15 in CD44 cleavage and glycocalyx shedding. An in vitro cleavage assay coupled with liquid chromatography-tandem mass spectrometry confirmed ADAM15 cleaved CD44 at His235-Thr236 bond. In ECs with ADAM15 knockdown, LPS-induced CD44 cleavage and TER reduction were greatly attenuated, whereas, ADAM15 overexpression exacerbated CD44 cleavage and TER response to LPS. Consistently, ADAM15 knockout in mice attenuated CLP-induced increase in plasma CD44. Intravital and electron microscopic images revealed ADAM15 deficiency prevented LPS-induced glycocalyx injury in cremaster and pulmonary microvasculatures. Functionally, ADAM15−/− mice with better-preserved glycocalyx exhibited resistance to LPS-induced vascular leakage, as evidenced by reduced albumin extravasation in pulmonary and mesenteric vessels. Importantly, in intact, functionally vital human lungs, perfusion of LPS induced a significant up-regulation of ADAM15, accompanied by elevated CD44 in the effluent and increased vascular permeability to albumin. Together, our data support the critical role of ADAM15 in mediating vascular barrier dysfunction during inflammation. Its mechanisms of action involve CD44 shedding and endothelial glycocalyx injury.
HSD3B1(1245A&gt;C) variant regulates dueling abiraterone metabolite effects in prostate cancer
Authors: Mohammad Alyamani, Hamid Emamekhoo, Sunho Park, Jennifer Taylor, Nima Almassi, Sunil Upadhyay, Allison Tyler, Michael P. Berk, Bo Hu, Tae Hyun Hwang, William Douglas Figg, Cody J. Peer, Caly Chien, Vadim S. Koshkin, Prateek Mendiratta, Petros Grivas, Brian Rini, Jorge Garcia, Richard J. Auchus, Nima Sharifi
Journal: Journal of Clinical Investigation (2018)

BACKGROUND. A common germline variant in HSD3B1(1245A>C) encodes for a hyperactive 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) missense that increases metabolic flux from extragonadal precursor steroids to DHT synthesis in prostate cancer. Enabling of extragonadal DHT synthesis by HSD3B1(1245C) predicts for more rapid clinical resistance to castration and sensitivity to extragonadal androgen synthesis inhibition. HSD3B1(1245C) thus appears to define a subgroup of patients who benefit from blocking extragonadal androgens. However, abiraterone, which is administered to block extragonadal androgens, is a steroidal drug that is metabolized by 3βHSD1 to multiple steroidal metabolites, including 3-keto-5α-abiraterone, which stimulates the androgen receptor. Our objective was to determine if HSD3B1(1245C) inheritance is associated with increased 3-keto-5α-abiraterone synthesis in patients.
Testicular cancer: symptoms for urgent referral are identified
Authors: Jacqui Wise
Journal: BMJ (2018)

Contrary to traditional teaching, painful testicular enlargement is a strong predictor of testicular cancer, a general practice study has shown.

The research, published in the British Journal of General Practice ,1 found that testicular enlargement—a lump or swelling—was the biggest risk factor for testicular cancer.

Funded by the National Institute for Health Research, the study looked at the symptoms of testicular cancer reported in general practice surgeries. Researchers from the University of Exeter Medical School compared electronic patient records of 1398 men who …
Abstract 800: ABBV-744, a first-in-class and highly selective inhibitor of the second bromodomain of BET family proteins, displays robust activities in preclinical models of acute myelogenous leukemia
Authors: Xiaoyu Lin, Xiaoli Huang, Richard Bellin, Emily Faivre, Paul Hessler, Lloyd Lam, Mai Ha Bui, Denise Wilcox, Tamar Uziel, Debra C. Ferguson, Terrance J. Magoc, Daniel H. Albert, Keith F. McDaniel, Warren Kati, Yu Shen
Journal: Cancer Research (2018)

Abstract Many small-molecule inhibitors that target both bromodomains of the BET family proteins (pan BET inhibitors) are undergoing studies in clinical trials. Emerging data are beginning to suggest that clinical responses to these pan BET inhibitors in subsets of hematologic malignancies may be modest and short lived, perhaps due, at least in part, to tolerability issues that limit dosing levels. We hypothesized that selective inhibition of four of the eight bromodomains in BET family proteins might retain the anticancer activities in certain tumor subsets while alleviating some of the tolerability liabilities of pan BET inhibitors, thus possibly providing better therapeutic benefits. ABBV-744 is a highly selective inhibitor for the second bromodomain (BDII) of the four BET family proteins, exhibiting greater than 300-fold more potent binding affinity to the BDII bromodomain of BRD4 relative to the first bromodomain (BDI) of BRD4. In contrast to the broad antiproliferative activities observed with pan BET inhibitors, ABBV-744 only displayed significant antiproliferative activities in a limited number of cancer cell lines, including AML and androgen receptor (AR)-positive prostate cancer. Studies in AML xenograft models demonstrated antitumor efficacy for ABBV-744 that was comparable to the pan-BET inhibitor ABBV-075 but with improved tolerability. Taken together, these results suggest that ABBV-744 could be a promising second-generation BET inhibitor for AML therapy. Affiliation: Oncology Discovery, AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064. Disclosures: All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication. Citation Format: Xiaoyu Lin, Xiaoli Huang, Richard Bellin, Emily Faivre, Paul Hessler, Lloyd Lam, Mai Ha Bui, Denise Wilcox, Tamar Uziel, Debra C. Ferguson, Terrance J. Magoc, Daniel H. Albert, Keith F. McDaniel, Warren Kati, Yu Shen. ABBV-744, a first-in-class and highly selective inhibitor of the second bromodomain of BET family proteins, displays robust activities in preclinical models of acute myelogenous leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 800.
Industry Payments to Physician Specialists Who Prescribe Repository Corticotropin
Authors: Daniel M. Hartung, Kirbee Johnston, David M. Cohen, Thuan Nguyen, Atul Deodhar, Dennis N. Bourdette
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Despite great expense and little evidence supporting use over corticosteroids, prescriptions for repository corticotropin (H. P. Acthar Gel; Mallinckrodt Pharmaceuticals) have increased markedly. Aggressive sales tactics and payments from the manufacturer may influence prescribing behavior for this expensive medication. <h3>Objective</h3> To characterize industry payments to physician specialists who prescribe corticotropin in the Medicare program. <h3>Design, Setting, and Participants</h3> This study was a cross-sectional analysis of Centers for Medicare &amp; Medicaid Services 2015 Part D prescribing data linked to 2015 Open Payments data. Nephrologists, neurologists, and rheumatologists with more than 10 corticotropin prescriptions (frequent prescribers) in 2015 were included. <h3>Exposures</h3> Frequency, category, and magnitude of corticotropin-related payments from Mallinckrodt recorded in the Open Payments database. <h3>Main Outcomes and Measures</h3> Frequency, category, and magnitude of corticotropin-related payments from Mallinckrodt, as well as corticotropin prescriptions and expenditures for Medicare beneficiaries. <h3>Results</h3> Of the 235 included physicians, 65 were nephrologists; 59, neurologists; and 111, rheumatologists. A majority of frequent corticotropin prescribers (207 [88%]) received corticotropin-related payments from Mallinckrodt. The median (range) total payment for 2015 was $189 ($11-$138 321), with the highest payments ranging from $56 549 to $138 321 across the specialties. More than 20% of frequent prescribers received more than $10 000 and the top quartile of recipients received a median (range) of $33 190 ($9934-$138 321) in total payments per prescriber. Payments for compensation for services other than consulting contributed the most to the total amount. Mallinckrodt payments were positively associated with greater Medicare spending on corticotropin (β = 1.079; 95% CI, 1.044-1.115;<i>P</i> &lt; .001), with every $10 000 in payments associated with a 7.9% increase (approximately $53 000) in Medicare spending on corticotropin. There was no association between corticotropin-related payments and spending on prescriptions for synthetic corticosteroids. <h3>Conclusions and Relevance</h3> In this study, most nephrologists, neurologists, and rheumatologists who frequently prescribe corticotropin received corticotropin-related payments from Mallinckrodt. These findings suggest that financial conflicts of interest may be driving use of corticotropin in the Medicare program.
Adult farming exposure does not protect against sensitization to the storage mite Lepidoglyphus destructor
Authors: Grethe Elholm, Vivi Schlünssen, Gert Doekes, Ioannis Basinas, Øyvind Omland, Pernille Milvang Grønager, Torben Sigsgaard
Journal: Allergy (2018)

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