tbuckley/cabot-search huggingface dataset:
Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer
Authors: Karim Fizazi, Kim N. Chi, Johann S. de Bono, Leonard G. Gomella, Kurt Miller, Dana E. Rathkopf, Charles J. Ryan, Howard I. Scher, Neal D. Shore, Peter De Porre, Anil Londhe, Tracy McGowan, Nonko Pelhivanov, Robert Charnas, Mary B. Todd, Bruce Montgomery
Journal: European Urology (2016)
Cigarette Smoke Inhalation Studies in Inbred Syrian Golden Hamsters2
Authors: P. Bernfeld, F. Homburger, E. Soto, K. J. Pai
Journal: JNCI Journal of the National Cancer Institute (1979)

Invasive carcinoma of the larynx was induced in 36.8% of inbred Syrian golden hamsters from strain B10® 15.16, susceptible to this type of cancer when exposed to smoke from reference filter cigarettes for 59–80 weeks. Nearly half the animals (47.4%) showed laryngeal cancer, including noninvasive carcinoma and carcinoma in situ, which occurred with daily smoke exposures (twice a day for 12 min each time, for 27 sec out of each min) 7 days a week at smoke concentrations of 22%. When the smoke concentration was reduced to 11%, the number of induced lesions was reduced proportionately. When a portion of tobacco was replaced in the cigarettes by a tobacco supplement, Cytrel (a trademark of the Celanese Corp., Charlotte, N.C.), a reduction of carcinogenesis proportionate to the Cytrel content of the cigarette took place. Smoke from cigarettes containing only Cytrel and no tobacco induced no carcinomas under the conditions used. Other dose-related changes observed were laryngeal papillomas, laryngeal epithelial hyperplasia, tracheal epithelial hyperplasia, and metaplasia and accumulation of alveolar macrophages. Tar deposition in lungs and larynges was determined in a separate study by means of a marker, decachlorobiphenyl, added to the cigarettes. Admixture of Cytrel to cigarettes reduced tar deposition in the respiratory tract, which paralleled the decrease in the incidence of laryngeal carcinoma. However, the amounts of tar deposited in the larynx when 100% Cytrel was smoked were still significant, even though no carcinomas were observed. Thus smoke from Cytrel tobacco supplement may be less carcinogenic than equal amounts of tobacco smoke.
Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis
Authors: Eric M Thompson, Thomas Hielscher, Eric Bouffet, Marc Remke, Betty Luu, Sridharan Gururangan, Roger E McLendon, Darell D Bigner, Eric S Lipp, Sebastien Perreault, Yoon-Jae Cho, Gerald Grant, Seung-Ki Kim, Ji Yeoun Lee, Amulya A Nageswara Rao, Caterina Giannini, Kay Ka Wai Li, Ho-Keung Ng, Yu Yao, Toshihiro Kumabe, Teiji Tominaga, Wieslawa A Grajkowska, Marta Perek-Polnik, David C Y Low, Wan Tew Seow, Kenneth T E Chang, Jaume Mora, Ian F Pollack, Ronald L Hamilton, Sarah Leary, Andrew S Moore, Wendy J Ingram, Andrew R Hallahan, Anne Jouvet, Michelle Fèvre-Montange, Alexandre Vasiljevic, Cecile Faure-Conter, Tomoko Shofuda, Naoki Kagawa, Naoya Hashimoto, Nada Jabado, Alexander G Weil, Tenzin Gayden, Takafumi Wataya, Tarek Shalaby, Michael Grotzer, Karel Zitterbart, Jaroslav Sterba, Leos Kren, Tibor Hortobágyi, Almos Klekner, Bognár László, Tímea Pócza, Peter Hauser, Ulrich Schüller, Shin Jung, Woo-Youl Jang, Pim J French, Johan M Kros, Marie-Lise C van Veelen, Luca Massimi, Jeffrey R Leonard, Joshua B Rubin, Rajeev Vibhakar, Lola B Chambless, Michael K Cooper, Reid C Thompson, Claudia C Faria, Alice Carvalho, Sofia Nunes, José Pimentel, Xing Fan, Karin M Muraszko, Enrique López-Aguilar, David Lyden, Livia Garzia, David J H Shih, Noriyuki Kijima, Christian Schneider, Jennifer Adamski, Paul A Northcott, Marcel Kool, David T W Jones, Jennifer A Chan, Ana Nikolic, Maria Luisa Garre, Erwin G Van Meir, Satoru Osuka, Jeffrey J Olson, Arman Jahangiri, Brandyn A Castro, Nalin Gupta, William A Weiss, Iska Moxon-Emre, Donald J Mabbott, Alvaro Lassaletta, Cynthia E Hawkins, Uri Tabori, James Drake, Abhaya Kulkarni, Peter Dirks, James T Rutka, Andrey Korshunov, Stefan M Pfister, Roger J Packer, Vijay Ramaswamy, Michael D Taylor
Journal: The Lancet Oncology (2016)
Inflammatory bowel disease and risk of mortality in COPD
Authors: Maria Vutcovici, Alain Bitton, Pierre Ernst, Abbas Kezouh, Samy Suissa, Paul Brassard
Journal: European Respiratory Journal (2016)

Patients with chronic obstructive pulmonary disease (COPD) have higher incidence and prevalence of other chronic inflammatory diseases, including inflammatory bowel disease (IBD). We assessed whether IBD onset increases mortality risk in patients with COPD or asthma-associated COPD. Two population-based cohorts of COPD and asthma-COPD subjects were identified using the administrative health databases in Québec, Canada, 1990–2007. Death records were retrieved from the death certificate registry. Cox proportional hazards models were used to assess the impact of newly developed IBD on mortality risk. The COPD and asthma-COPD cohorts included 273 208 and 26 575 patients, respectively, of which 697 and 119 developed IBD. IBD increased the risk of all-cause mortality in both COPD (hazard ratio 1.23, 95% CI 1.09–1.4) and asthma-COPD (hazard ratio 1.65, 95% CI 1.23–2.22). In asthma-COPD patients, IBD increased the risk of mortality from respiratory conditions (hazard ratio 2.18, 95% CI 1.31–3.64); in COPD patients, IBD increased the risk of death from digestive conditions (hazard ratio 4.45, 95% CI 2.39–8.30). IBD is a risk factor for mortality in patients with pre-existing COPD or asthma-COPD. IBD increased mortality by respiratory and digestive conditions in patients with asthma-COPD and COPD, respectively.
Abstract 15508: Animal Model of Fetal Aortic Valvuloplasty: Technical Success Maximized With Combination of Perventricular and Transhepatic Access
Authors: Alan W Nugent, Michael Talcott, Adrian Dyer, Reenu Eapen, Robert C Kowal, Kevin Magee
Journal: Circulation (2013)

Objectives: Fetal aortic valvuloplasty via direct perventricular puncture is reported in humans, complicated by bradycardia and hemopericardium. There are also limitations related to fetal lie. The...
Prevalence of Respiratory Viruses in Patients with Acute Respiratory Infections in Korea
Authors: Jin-sung Park, Hee-Dong Jung, Hyang-Min Jung, Sung-Soon Kim, Chang-Keun Kim
Journal: Journal of Allergy and Clinical Immunology (2016)

Acute Respiratory Infections (ARI) are the most common infectious disease that caused significant morbidity and mortality with consequently an enormous economic burden. Since Dec 2005, Korea Centers for Disease Control and Prevention has been running surveillance system KINRESS(Korea Influenza and Respiratory Virus Surveillance System) for the detection of major respiratory viruses. We investigated the viral pathogen causing ARI in Korea, 2013. We performed multiplex PCR/RT-PCR on respiratory specimen(throat oral nasal swab) to determine the prevalence of 14 viruses including adenovirus(HAdV), parainfluenza virus(HPIV) 1, 2, 3, respiratory syncytial virus(HRSV) A and B, influenza virus(IFV) H1N1pdm09, H3N2, B, human coronavirus(HCoV) 229E, NL63 and OC43, human rhinovirus (HRV), human bocavirus(HBoV) and human metapneumovirus(HMPV). And the statistical analysis was performed to investigate the characteristics of age-distribution, seasonality, and clinical features of ARI patients. Respiratory viruses were detected by 49.4% of enrolled patients(n=15,050), and 1-5 year-old age group accounted for almost. However, significant differences were not observed depending on the age group of virus detection rate. HAdV, HPIV, HRSV, HCoV, HBoV and HMPV were mainly detected from under 5 years old. IFV were mainly detected on over 6 years old. HRSV, IFV, HCoV infections were peaked in winter season. In summer, incidence of HPIV and HBoV were increased. When we analyzed the association of viral infection with clinical feature, almost infections were correlated with fever, cough and runny nose. Our data suggest that there was a meaningful relationship between viral infection and typical manifestation of known clinical feature as well as seasonality and age distribution.
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Authors: Aharon Helman, Agnes Klochendler, Narmen Azazmeh, Yael Gabai, Elad Horwitz, Shira Anzi, Avital Swisa, Reba Condiotti, Roy Z Granit, Yuval Nevo, Yaakov Fixler, Dorin Shreibman, Amit Zamir, Sharona Tornovsky-Babeay, Chunhua Dai, Benjamin Glaser, Alvin C Powers, A M James Shapiro, Mark A Magnuson, Yuval Dor, Ittai Ben-Porath
Journal: Nature Medicine (2016)
Inhibition of Growth of Human Breast Cancer Cell Line MCF-7 by Serum Derived From Calcium Chloride-Clotted Plasma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: E V Gaffney, M A Grimaldi, D A Pigott, M Dell'Aquila
Journal: JNCI Journal of the National Cancer Institute (1980)

The growth of MCF-7 cells, established from a metastatic mammary carcinoma. and of HBL-100 cells, derived from a primary culture of human milk, was examined in medium supplemented with whole blood serum (WBS). defibrinogenated plasma, and plasma-derived serum (PDS). PDS obtained from platelet-poor plasma collected with the anticoagulant citrate phosphate dextrose and clotted by the addition of calcium chloride did not promote the growth of MCF-7 cells as well as did WBS or platelet-poor defibrinogenated plasma alone. Growth-inhibitory activity was observed when final cell densities in the presence of PDS combined with fetal bovine serum (FBS) were compared with those in control cultures maintained in FBS alone. The level of this activity in PDS varied among donors. Inhibition was not observed with HBL-100 cells. Calcium chloride did not induce inhibitory activity when added to WBS or defibrinogenated plasma, and platelet components did not alter the level of inhibition in PDS. However. platelet extracts did affect the expression of inhibition when added to plasma before clotting. Activity was diminished following dialysis of PDS. which suggested that inhibition stemmed from a small-molecular-weight factor for which expression depended on the mechanism of plasma coagulation.
Toxin Immunoassays and<i>Clostridium difficile</i>Infection
Authors: Geraldine Moloney, Brian O'Connell, Thomas R. Rogers
Journal: JAMA Internal Medicine (2016)

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
Comparison of the risk prediction systems POSSUM and P-POSSUM with the Surgical Risk Scale: A prospective cohort study of 721 patients
Authors: Sergio González-Martínez, Montserrat Martín-Baranera, Isidro Martí-Saurí, Nuria Borrell-Grau, José M. Pueyo-Zurdo
Journal: International Journal of Surgery (2016)
The unclear zone in phase II clinical trials
Authors: S. M. Allegro, S. J. Hotte
Journal: Journal of Clinical Oncology (2008)

6519 Background: The transition to clinical use of a new oncology drug is reliant upon phase II trials. Typically, a cohort of patients is treated and the outcomes are related to a prespecified target. If the results meet the target, it is declared worthy of further study, otherwise, further development is likely stopped. This method is often referred to as the ‘go/no-go’ decision algorithm and may be based on the Simon-Fleming model. With this model, the null and alternative hypotheses create a grey zone where results of a trial can fall below the alternative hypothesis and above the null hypothesis. This study was conducted to evaluate whether there is congruence with numerical results of phase II trials and the ultimate conclusion. Methods: A review of phase II clinical trials was conducted. Pubmed was searched for 2006 and 2007 original reports of phase II trials in cancer patients. The alternative and null hypotheses for primary endpoints were noted, along with confidence intervals (CI). These were then compared to the final written conclusions and concordance and discordance rates were calculated. Results: A total of 152 phase II trials were reviewed, 69 from the year 2006 and 117 from the year 2007. Six trials were multi- armed with independently tested hypotheses. The point estimate values were negative in 45/152 (30%), positive in 60/152 (39%) and within the grey zone in 47/152 (31%). If 95% CIs were used, 12/152 (8%) of trials were negative, 86/152 (57%) were positive and 51/152 (34%) were in the grey zone. Three of 152 (1%) papers had 90% CI reported that also fell in the grey zone. When point estimates were compared to the studies' conclusive statements, the rate of concordance was 93/152 (61%), the rate of discordance was 52/152 (34%) and there were 6/152 (4%) unclear conclusions and 1/152 incomplete trial (<1%). If CIs were included, the concordance rate was 11/152 (7%) and the discordance rate was 87/152 (57%). Forty-eight of 152 (32%) were not analyzable because no CI data was provided. Conclusions: There are inconsistencies and ambiguities in the conclusions drawn from phase II trials, particularly when results are neither in the ‘go‘ or ‘no- go‘ regions. This may make the integration of phase II trials in phase III trial development strategies difficult and clear guidelines need to be implemented for the reporting of these studies. No significant financial relationships to disclose.
Phase II Study of a Non-Platinum–Containing Doublet of Paclitaxel and Pemetrexed with Bevacizumab as Initial Therapy for Patients with Advanced Lung Adenocarcinomas
Authors: M.C. Pietanza, Matthew D. Hellmann, John J. Fiore, Stephanie Smith-Marrone, Ethan M. Basch, Lawrence H. Schwartz, Michelle S. Ginsberg, Marwan Shouery, Samantha K. Newman, Mary Shaw, Lauren J. Rogak, Alex E. Lash, Patrick Hilden, Mark G. Kris
Journal: Journal of Thoracic Oncology (2016)
YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal Fibrogenesis
Authors: Stephen G. Szeto, Masahiro Narimatsu, Mingliang Lu, Xiaolin He, Ahmad M. Sidiqi, Monica F. Tolosa, Lauren Chan, Krystale De Freitas, Janne Folke Bialik, Syamantak Majumder, Stellar Boo, Boris Hinz, Qinghong Dan, Andrew Advani, Rohan John, Jeffrey L. Wrana, Andras Kapus, Darren A. Yuen
Journal: Journal of the American Society of Nephrology (2016)

Like many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF- β responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF- β . In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF- β –induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF- β stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF- β to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF- β /Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF- β signaling and renal fibrogenesis.
US drug costs are rising faster than overall health spending, officials report
Authors: Michael McCarthy
Journal: BMJ (2016)

Spending on prescription drugs in the United States has risen sharply in recent years and is projected to consume an increasing share of overall healthcare, says a government report.1

The report, released 8 March, came on the same day that Medicare officials announced a new proposal aimed at curtailing spending on expensive specialty drugs. The cost of drugs is a growing concern in the US, with one recent poll finding that 77% of adults thought it should be a priority to ensure that high cost drugs were …
Telemonitoring in patients with chronic respiratory insufficiency: expectations deluded?
Authors: Michele Vitacca
Journal: Thorax (2016)

Chronic respiratory insufficiency represents the advanced stage of a heterogeneous group of respiratory diseases, including COPD, which have an associated high cost burden.1 Modern information communication technologies offer new options to deliver remote specialised healthcare, among which telemonitoring, a complex intervention that includes both the electronic transmission of patient information to the healthcare system and the follow-up response by a healthcare professional. The rationale for telemonitoring development in patients presenting with chronic respiratory insufficiency with or without home mechanical ventilation need is related to: (1) progressive ageing of the patient population carrying with it an increased burden of care at home; (2) technological advances; (3) increased healthcare consumption and the need to cut costs; (4) the increasing number of home mechanical ventilation patients across Europe;2 (5) difficulties associated with hospital discharge, with tremendous physical and psychological burden for caregivers of home mechanical ventilation patients;3 and (6) the opportunity that telemonitoring offers of early remote detection of signs and symptoms of chronic respiratory insufficiency decompensation,4 and at-distance tailoring and monitoring of mechanical ventilation and education reinforcement for the patient and caregiver. Given the cost of telemonitoring in terms of human resources, equipment and patients’ time, strong evidence of its cost-effectiveness is required, in particular as regards the impact of an earlier detection of relapses of chronic conditions. Unfortunately, decision makers, for example, the healthcare authorities, are rushing to introduce telemonitoring in response to the pressure to reduce hospitalisations among patients with chronic diseases, without first carefully weighing up all the evidence. In the last decade, several studies focusing on the effects of various tele-management programmes for patients with chronic respiratory insufficiency (with COPD being the main diagnosis) have been published.5–8

A few years ago, Wooton9 concluded that the evidence base for telemedicine in managing chronic …
Soluble B-Cell Maturation Antigen Mediates Tumor-Induced Immune Deficiency in Multiple Myeloma
Authors: Eric Sanchez, Abigail Gillespie, George Tang, Morgan Ferros, Nika Manik Harutyunyan, Suzie Vardanyan, Jillian Gottlieb, Mingjie Li, Cathy S. Wang, Haiming Chen, James R. Berenson
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Reduced uninvolved immunoglobulin (Ig) levels are a hallmark of multiple myeloma. We previously showed that B-cell maturation antigen (BCMA) is solubilized and at high levels in multiple myeloma patient serum. We hypothesize that soluble BCMA binds B-cell–activating factor (BAFF) preventing its function to stimulate late B cells, and would result in lower polyclonal antibody levels in these patients. Experimental Design: Mice were dosed with recombinant human BCMA (rhBCMA) and BCMA–BAFF complexes were analyzed in plasma, and its effects on antibody and Ig heavy chain mRNA levels determined. Using flow cytometry, BAFF binding to B cells was examined in the presence of rhBCMA and sera from multiple myeloma patients. In multiple myeloma sera, BCMA–BAFF complex formation and BCMA, IgA, IgG levels, and heavy–light chain isoform pair levels were determined. Results: rhBCMA–BAFF complexes formed in immune-competent and deficient mice. Mice with human multiple myeloma xenografts, which contain plasma hBCMA and hBCMA–BAFF complexes, showed reduced plasma-free BAFF levels. rhBCMA administered to immune competent mice markedly reduced plasma IgA, IgG, and IgM levels and splenic Ig heavy chain mRNA levels. In serum from multiple myeloma patients, BCMA–BAFF complexes were detected and BAFF levels were reduced. Multiple myeloma patient sera containing BCMA prevented binding of BAFF to B cells. There is an inverse correlation between serum BCMA and uninvolved polyclonal Ig level in multiple myeloma patients. Conclusions: Our results show that soluble BCMA sequesters circulating BAFF, thereby preventing it from performing its signaling to stimulate normal B-cell and plasma cell development, resulting in reduced polyclonal antibody levels in multiple myeloma patients. Clin Cancer Res; 22(13); 3383–97. ©2016 AACR.
CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling
Authors: Haibo Sun, De-Chen Lin, Qi Cao, Xiao Guo, Helene Marijon, Zhiqiang Zhao, Sigal Gery, Liang Xu, Henry Yang, Brendan Pang, Victor Kwan Min Lee, Huey Jin Lim, Ngan Doan, Jonathan W. Said, Peiguo Chu, Anand Mayakonda, Tom Thomas, Charles Forscher, Erkan Baloglu, Sharon Shacham, Raja Rajalingam, H. Phillip Koeffler
Journal: Cancer Research (2016)

Abstract Ewing sarcoma (EWS) is an aggressive bone malignancy that mainly affects children and young adults. The mechanisms by which EWS (EWSR1) fusion genes drive the disease are not fully understood. CRM1 (XPO1) traffics proteins from the nucleus, including tumor suppressors and growth factors, and is overexpressed in many cancers. A small-molecule inhibitor of CRM1, KPT-330, has shown therapeutic promise, but has yet to be investigated in the context of EWS. In this study, we demonstrate that CRM1 is also highly expressed in EWS. shRNA-mediated or pharmacologic inhibition of CRM1 in EWS cells dramatically decreased cell growth while inducing apoptosis, cell-cycle arrest, and protein expression alterations to several cancer-related factors. Interestingly, silencing of CRM1 markedly reduced EWS–FLI1 fusion protein expression at the posttranscriptional level and upregulated the expression of the well-established EWS-FLI1 target gene, insulin-like growth factor binding protein 3 (IGFBP3), which inhibits IGF-1. Accordingly, KPT-330 treatment attenuated IGF-1–induced activation of the IGF-1R/AKT pathway. Furthermore, knockdown of IGFBP3 increased cell growth and rescued the inhibitory effects on IGF-1 signaling triggered by CRM1 inhibition. Finally, treatment of EWS cells with a combination of KPT-330 and the IGF-1R inhibitor, linsitinib, synergistically decreased cell proliferation both in vitro and in vivo. Taken together, these findings provide a strong rationale for investigating the efficacy of combinatorial inhibition of CRM1 and IGF-1R for the treatment of EWS. Cancer Res; 76(9); 2687–97. ©2016 AACR.