tbuckley/cabot-search huggingface dataset:
Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial
Authors: Jules A A C Heuberger, Joris I Rotmans, Pim Gal, Frederik E Stuurman, Juliëtte van 't Westende, Titiaan E Post, Johannes M A Daniels, Matthijs Moerland, Peter L J van Veldhoven, Marieke L de Kam, Herman Ram, Olivier de Hon, Jelle J Posthuma, Jacobus Burggraaf, Adam F Cohen
Journal: The Lancet Haematology (2017)
The international open-label early-access study of trifluridine/tipiracil (TAS-102) in patients with pretreated metastatic colorectal cancer (phase IIIb)
Authors: Alfredo Falcone, Jean-François Seitz, Timothy Price, Lucjan Wyrwicz, Alice Dorbon, Natividad Lopez Busto, Nadjat Mounedji, Eric Van Cutsem
Journal: Annals of Oncology (2017)
Abstract 70: Novel Multi-target Compound, Agonist of Adenosine Receptor and Inhibitor of Phosphodiesterase 5, Ameliorates Monocrotaline-induced Pulmonary Hypertension in Rats
Authors: Gisele Zapata-Sudo, Allan K Alencar, Jaqueline S da Silva, Eliezer J Barreiro, Carlos A Fraga, Emanuelle B Ferraz, Jose H Nascimento, Roberto T Sudo
Journal: Circulation Research (2015)

Aims: Pulmonary hypertension (PH) is a disease that results in right ventricular (RV) dysfunction and premature death. This work investigated the effects of LASSBio-1386, a compound with dual target, activation of the adenosine A 2A receptor and inhibition of phosphodiesterase 5 in rats with monocrotaline (MCT)-induced PH. Methods and Results: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Male Wistar rats received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Experimental groups were: control, MCT + vehicle (DMSO), MCT + LASSBio-1386 (100 μmol/kg/day p.o.) and MCT + Sildenafil (100 μmol/kg/day p.o.). Animals were treated with vehicle or drug for 14 days after the onset of disease (n = 6 per group). Treadmill test and transthoracic echocardiography were performed to access exercise capacity and cardiac function, respectively. Right ventricular systolic pressure (RVSP) and ratio between RV and body weight (RV/BW) were analyzed. Exercise capacity (m.kg) was reduced from 1336.2 ± 82.2(control) to 479.7 ± 75.5 (MCT+ vehicle) and recovered to 1357.0 ± 87.8 and 1221.0 ± 96.8 after treatment with LASSBio-1386 and sildenafil, respectively. Pulmonary acceleration time (PAT) (ms) was reduced from 45.3 ± 0.8 (control) to 21.9 ± 0.3 in MCT + vehicle group ( P &lt; 0.05) and restored to 42.9 ± 0.7 in MCT + LASSBio-1386 group, but it was only partially restored to 37.8 ± 1.3 (ms) in MCT + Sildenafil-treated group. RVSP (mmHg) was increased from 27.1 ± 0.7 (control) to 52.9 ± 1.5 in the PH rats and was reduced to 29.1 ± 1.0 and to 31.8 ± 0.6 after treatment with LASSBio-1386 and sildenafil. PH induced an increase of RV/BW (mg/g) from 0.62 ± 0.03 (control) to 1.81 ± 0.20 which was reduced to 0.70 ± 0.07 after administration of LASSBio-1386. Sildenafil treatment did not reverse the RV hypertrophy in PH rats (RV/BW = 1.52 ± 0.10 mg/g). Conclusions: LASSBio-1386 was effective to prevent RV dysfunction and exercise intolerance indicating important implications for ongoing clinical evaluation of multi-target drugs for the treatment of PAH.
The Spontaneous Adhesion of BMMC onto Self‐Assembled Peptide Nanoscaffold without Activation Inhibits Its IgE‐Mediated Degranulation
Authors: Lei Lu, Narcy Arizmendi, Marianna Kulka, Larry D. Unsworth
Journal: Advanced Healthcare Materials (2017)

Mast cells play a distinct role in the innate immune response. Engineered microenvironments for the express purpose of influencing mast cell activity will provide a novel means of designing biomaterials, as well as a means to systematically investigate mast cell biology in a 3D setting. Here, the effect of nanoscaffolds composed of self‐assembling peptides, namely (RADA) 4 , on bone‐marrow‐derived murine mast cell (BMMC) activity is reported. Unlike most studies that stimulate mast cells to induce adhesion, this results show that BMMCs spontaneously adhere to the artificial nanoscaffold without initiating their activation. It is observed that the classical immunoglobulin (IgE) antigen‐mediated degranulation of adhered BMMC is inhibited by the nanoscaffold, while non‐IgE (A23187)‐induced degranulation is unaffected. The inhibition of IgE–antigen‐mediated degranulation is likely a result of inhibited molecular diffusion within the matrix; antigen diffusion, IgE–FcεRI complex shuttling, and/or formation of multiple IgE–FcεRI clusters may be physically hindered in the presence of the polyvalent nanofiber network. Moreover, the IgE/antigen‐induced inflammatory cytokine tumor necrosis factor α release from adherent BMMCs is significantly reduced likely due to interaction with the nanofiber matrix. This work is considered the first step in quantifying mast cell activity in artificial matrices composed of self‐assembling peptides.
Baseline incidence of intussusception in early childhood before rotavirus vaccine introduction, the Netherlands, January 2008 to December 2012
Authors: Kartini Gadroen, Jeanet M Kemmeren, Patricia CJ Bruijning-Verhagen, Sabine MJM Straus, Daniel Weibel, Hester E de Melker, Miriam CJM Sturkenboom
Journal: Eurosurveillance (2017)

Intussusception is a rare, potentially life-threatening condition in early childhood. It gained attention due to an unexpected association with the first rotavirus vaccine, RotaShield, which was subsequently withdrawn from the market. Across Europe, broad variations in intussusception incidence rates have been reported. This study provides a first estimate of intussusception incidence in young children in the Netherlands from 1 January 2008 to 31 December 2012, which could be used for future rotavirus safety monitoring. Our estimates are based on two different sources: electronic medical records from the primary healthcare database (IPCI), as well as administrative data from the Dutch hospital register (LBZ). The results from our study indicate a low rate of intussusception. Overall incidence rate in children &lt; 36 months of age was 21.2 per 100,000 person-years (95% confidence interval (CI): 12.5–34.3) based on primary healthcare data and 22.6 per 100,000 person-years (95% CI: 20.9–24.4) based on hospital administrative data. The estimates suggest the upper and lower bound of the expected number of cases.
Retinoic Acid Receptor Alpha Expression Drives Cell-Cycle Progression and Is Associated with Increased Sensitivity to Retinoids in Peripheral T-Cell Lymphoma
Authors: Rebecca L Boddicker, Xueju Wang, Surendra Dasari, Grzegorz S. Nowakowski, Konstantinos N Lazaridis, Eric D Wieben, Marshall E. Kadin, Andrew L Feldman
Journal: Blood (2016)
Abstract P189: RhoA Functions as an Antihypertrophic Switch in the Mouse Heart
Authors: Davy Vanhoutte, Jop Van Berlo, Allen J York, Yi Zheng, Jeffery D Molkentin
Journal: Circulation Research (2011)

Background. Small GTPase RhoA has been previously implicated as an important signaling effector within the cardiomyocyte. However, recent studies have challenged the hypothesized role of RhoA as an effector of cardiac hypertrophy. Therefore, this study examined the in vivo role of RhoA in the development of pathological cardiac hypertrophy. Methods and results . Endogenous RhoA protein expression and activity levels (GTP-bound) in wild-type hearts were significantly increased after pressure overload induced by transverse aortic constriction (TAC). To investigate the necessity of RhoA within the adult heart, RhoA-LoxP-targeted (RhoA flx/flx ) mice were crossed with transgenic mice expressing Cre recombinase under the control of the endogenous cardiomyocyte-specific β-myosin heavy chain (β-MHC) promoter to generate RhoA βMHC-cre mice. Deletion of RhoA with β-MHC-Cre produced viable adults with &gt; 85% loss of RhoA protein in the heart, without altering the basic architecture and function of the heart compared to control hearts, at both 2 and 8 months of age. However, subjecting RhoA βMHC-cre hearts to 2 weeks of TAC resulted in marked increase in cardiac hypertrophy (HW/BW (mg/g): 9.5 ± 0.3 for RhoA βMHC-cre versus 7.7 ± 0.4 for RhoA flx/flx ; and cardiomyocyte size (mm 2 ): 407 ± 21 for RhoA βMHC-cre versus 262 ± 8 for RhoA flx/flx ; n ≥ 8 per group; p&lt;0.01) and a significantly increased fibrotic response. Moreover, RhoA βMHC-cre hearts transitioned more quickly into heart failure whereas control mice maintained proper cardiac function (fractional shortening (%): 23.3 ± 1.2 for RhoA βMHC-cre versus 29.3 ± 1.2 for RhoA flx/flx ; n ≥ 8 per group; p&lt;0.01; 12 weeks after TAC). The latter was further associated with a significant increase in lung weight normalized to body weight and re-expression of the cardiac fetal gene program. In addition, these mice also displayed greater cardiac hypertrophy in response to 2 weeks of angiotensinII/phenylephrine infusion. Conclusion. These data identify RhoA as an antihypertrophic molecular switch in the mouse heart.
Activation of WEE1 confers resistance to PI3K inhibition in glioblastoma
Authors: Shaofang Wu, Shuzhen Wang, Feng Gao, Luyuan Li, Siyuan Zheng, W K Alfred Yung, Dimpy Koul
Journal: Neuro-Oncology (2017)

Oncogenic activation of phosphatidylinositol-3 kinase (PI3K) signaling plays a pivotal role in the development of glioblastoma (GBM). However, pharmacological inhibition of PI3K has so far not been therapeutically successful due to adaptive resistance through a rapid rewiring of cancer cell signaling. Here we identified that WEE1 is activated after transient exposure to PI3K inhibition and confers resistance to PI3K inhibition in GBM. Patient-derived glioma-initiating cells and established GBM cells were treated with PI3K inhibitor or WEE1 inhibitor alone or in combination, and cell proliferation was evaluated by CellTiter-Blue assay. Cell apoptosis was analyzed by TUNEL, annexin V staining, and blotting of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. Both subcutaneous xenograft and orthotropic xenograft studies were conducted to evaluate the effects of the combination on tumorigenesis; the tumor growth was monitored by bioluminescence imaging, and tumor tissue was analyzed by immunohistochemistry to validate signaling changes. PI3K inhibition activates WEE1 kinase, which in turn phosphorylates cell division control protein 2 homolog (Cdc2) at Tyr15 and inhibits Cdc2 activity, leading to G2/M arrest in a p53-independent manner. WEE1 inhibition abrogated the G2/M arrest and propelled cells to prematurely enter into mitosis and consequent cell death through mitotic catastrophe and apoptosis. Additionally, combination treatment significantly suppressed tumor growth in a subcutaneous model but not in an intracranial model due to limited blood–brain barrier penetration. Our findings highlight WEE1 as an adaptive resistant gene activated after PI3K inhibition, and inhibition of WEE1 potentiated the effectiveness of PI3K targeted inhibition, suggesting that a combinational inhibition of WEE1 and PI3K might allow successful targeted therapy in GBM.
the Impact of Clonal Dynamics on Prognosis and Outcome in Myelodysplastic Syndromes
Authors: Hideki Makishima, Tetsuichi Yoshizato, Kenichi Yoshida, Mikkael A. Sekeres, Tomas Radivoyevitch, Hiromichi Suzuki, Bartlomiej P Przychodzen, Yasunobu Nagata, Manja Meggendorfer, Masashi Sanada, Yusuke Okuno, Cassandra M. Hirsch, Teodora Kuzmanovic, Yusuke Shiozawa, Yusuke Sato, Aiko Sato-Otsubo, Thomas LaFramboise, Naoko Hosono, Yuichi Shiraishi, Kenichi Chiba, Claudia Haferlach, Wolfgang Kern, Hiroko Tanaka, Ines Gómez-Seguí, Holleh Husseinzadeh, Swapna Thota, Kathryn M. Guinta, Brittney Dienes, Tsuyoshi Nakamaki, Shuichi Miyawaki, Yogen Saunthararajah, Shigeru Chiba, Satoru Miyano, Lee-Yung Shih, Torsten Haferlach, Seishi Ogawa, Jaroslaw P Maciejewski
Journal: Blood (2016)
Neuroleptics for Delirium: More Research Is Needed
Authors: David Hui, Alan Valentine, Eduardo Bruera
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
<i>BRCA1/2</i> reversion mutations in prostate cancer identified from clinical tissue and liquid biopsy samples.
Authors: Sugganth Daniel, Erica Gornstein, Garrett Michael Frampton, James Sun, Samantha Morley, Andreas Heilmann, Prasanth Reddy, Jon Chung, James Suh, Shakti Ramkissoon, Eric Allan Severson, Jo-Anne Vergilio, Philip J. Stephens, Vincent A. Miller, Julia Andrea Elvin, Jeffrey S. Ross, Laurie M. Gay
Journal: Journal of Clinical Oncology (2017)

5024 Background: Prostate tumors with genomic alterations (GA) in BRCA1 or BRCA2 ( BRCA) may be sensitive to treatment with PARP inhibitors (PARPi). However, secondary reversion mutations (revGA) can arise that may restore BRCA function and underlie reduced sensitivity to PARPi or platinum (Pt)-based therapy. Comprehensive genomic profiling (CGP), using either tissue or liquid biopsies, can detect the variety of clinically relevant revGA that can arise. Methods: DNA extracted from FFPE tumor tissue or blood samples obtained during routine clinical care for 1911 patients with predominantly relapsed, refractory or metastatic prostate carcinoma was analyzed by hybrid-capture, next-generation sequencing for all classes of GA: base substitutions, indels, rearrangements, and copy number changes. RevGA were any GA that could restore the reading frame if in cis with a nonsense or frameshift (fs) GA. Results: 216/1911 (11.3% ± 1.4%) tumors had ≥1 deleterious BRCA GA. Of these, 7 samples harbored potential revGA in BRCA1 (1) or BRCA2 (6): prostate acinar adenocarcinoma (5), neuroendocrine carcinoma (1), or undifferentiated carcinoma (1). Of these, 2 samples were liquid biopsies (blood), 4 were FFPE tissue samples (liver), and 1 sample was a bone marrow core biopsy. All samples with revGA were metastases. Potential revGA were of 3 types: overlapping indel (4), compensatory fs (2), and missense (1). One case harbored 2 revGA, an overlapping indel and a compensatory fs. Alteration frequencies for TMPRSS2 (fusions), PTEN, and AR were similar with or without BRCA mutations; revGA-positive samples had a modest increase in PTEN alterations (42.9% vs 33.8%, NS). The frequency of CDK12 alterations was significantly reduced in BRCA-mutated tumors (0.9% vs 6.9%, p = 0.00002). Clinical histories for patients with reversion mutations will be presented. Conclusions: CGP of 1911 prostate carcinomas reveals ≥1 deleterious BRCA1/2 in 11.3% of samples. From these, a series of 7 cases, all metastases, with co-occurring potential revGA were identified. Although rare, revGA can be acquired during treatment and may underlie resistance to PARPi or Pt-based therapy. BRCA revGA can be detected from both tissue and liquid biopsies.
Regulation of TRAIL Mediated Apoptosis in Colorectal Cancer Cells
Authors: F MacCarthy, A Mohr, J Lee, RM Zwacka
Journal: Endoscopy (2006)

Aims: TNF Related Apoptosis Inducing Ligand (TRAIL) is a promising anti tumour agent in colorectal cancer with determinants of sensitivity associated with apoptosis signalling and cell cycle progression. The p53 protein is a prominent apoptosis and cell cycle regulator, therefore we investigated the effects of TRAIL on p53Wild Type (WT) and p53 Knockout (-/-) HCT 116 cells to assess differences in sensitivity and to correlate this with apoptosis and cell cycle mediators.
Climate services for health: predicting the evolution of the 2016 dengue season in Machala, Ecuador
Authors: Rachel Lowe, Anna M Stewart-Ibarra, Desislava Petrova, Markel García-Díez, Mercy J Borbor-Cordova, Raúl Mejía, Mary Regato, Xavier Rodó
Journal: The Lancet Planetary Health (2017)

BackgroundEl Niño and its effect on local meteorological conditions potentially influences interannual variability in dengue transmission in southern coastal Ecuador. El Oro province is a key dengue surveillance site, due to the high burden of dengue, seasonal transmission, co-circulation of all four dengue serotypes, and the recent introduction of chikungunya and Zika. In this study, we used climate forecasts to predict the evolution of the 2016 dengue season in the city of Machala, following one of the strongest El Niño events on record.MethodsWe incorporated precipitation, minimum temperature, and Niño3·4 index forecasts in a Bayesian hierarchical mixed model to predict dengue incidence. The model was initiated on Jan 1, 2016, producing monthly dengue forecasts until November, 2016. We accounted for misreporting of dengue due to the introduction of chikungunya in 2015, by using active surveillance data to correct reported dengue case data from passive surveillance records. We then evaluated the forecast retrospectively with available epidemiological information.FindingsThe predictions correctly forecast an early peak in dengue incidence in March, 2016, with a 90% chance of exceeding the mean dengue incidence for the previous 5 years. Accounting for the proportion of chikungunya cases that had been incorrectly recorded as dengue in 2015 improved the prediction of the magnitude of dengue incidence in 2016.InterpretationThis dengue prediction framework, which uses seasonal climate and El Niño forecasts, allows a prediction to be made at the start of the year for the entire dengue season. Combining active surveillance data with routine dengue reports improved not only model fit and performance, but also the accuracy of benchmark estimates based on historical seasonal averages. This study advances the state-of-the-art of climate services for the health sector, by showing the potential value of incorporating climate information in the public health decision-making process in Ecuador.FundingEuropean Union FP7, Royal Society, and National Science Foundation.
Prognostic utility of immune markers and validation of Immunoscore in stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance)
Authors: A. Sinicrope Frank, Qian Shi, Fabienne Hermitte, Erica Heying, B. Benson Al, Sharlene Gill, M. Goldberg Richard, Morton Kahlenberg, Suresh Nair, Anthony Shields, Dan Sargent, Jérôme Galon, R. Alberts Steven
Journal: Annals of Oncology (2017)
Relationship between physical activity and cardiovascular disease risk factors in cancer survivors.
Authors: Dong-Woo Kang, Kerry S. Courneya
Journal: Journal of Clinical Oncology (2016)

e13067 Background: Cardiovascular disease (CVD) is one of the most prevalent comorbidities among cancer survivors. Physical activity has been well established to positively control CVD risk factors in the general population. In this study, we investigated the association between physical activity and CVD risk factors in cancer survivors. Methods: Data from the 2007-2014 Korean National Health and Nutrition Examination Survey (KNHANES) were analyzed. Of the total sample from the survey, a total of 1,596 cancer survivors were included for data analysis. CVD risk factors included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), fasting glucose (FG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and triglycerides (TG). A high risk level associated with each factor was defined according to the Adult Treatment Panel (ATP) III guidelines. Physical activity was calculated on the basis of the total minutes spent in moderate and vigorous physical activity per week. Complex sample logistic regression analyses were used to identify whether there was a difference in CVD risks between physical activity groups. Results: Of a total of 1,596 subjects, 36.4% were men, mean age was 61.4±12.7, and mean BMI was 23.4±3.3. 48.8% of respondents were completely inactive (0 min/wk.), 22.0% were insufficiently active ( < 150 min/wk.), and 29.3% met the ACSM/ACS physical activity guidelines ( ≥ 150 min/wk.). Among CVD risk factors, the risks of low HDL-C (OR = 0.70, 95% CI = 0.52 – 0.94), high SBP (OR = 0.58, 95% CI = 0.44 – 0.76) and high TG (OR = 0.65, 95% CI = 0.48 – 0.89) were lower for those who met the physical activity guidelines compared to those who were completely inactive, after adjustment for age, sex, and body mass index. Furthermore, the OR for having two or more CVD risk factors was 0.55 (95% CI, 0.39 – 0.77). Conclusions: Meeting the physical activity guidelines ( ≥ 150 min/wk.) may mitigate CVD risk factors, and thereby reduce the risk that cancer survivors will develop.
A ten-year epidemiology of cancers managed at the hematology and oncology unit of a Haitian tertiary hospital from 2006 to 2015.
Authors: Flawendjee Djaweelentz Jacques, Joseph Bernard, Elsie Metellus Chalumeau
Journal: Journal of Clinical Oncology (2017)

e13061 Background: The recent epidemiology of cancers in Haiti is poorly known, since there is no national cancer registry. The data from GLOBOCAN 2012 are estimations that do not reflect the real cancer epidemiology in countries such as Haiti. The aim of this study was to determine the ten-year epidemiology of cancer cases managed at a Haitian tertiary hospital. Methods: A retrospective study based on the chart review of cancer cases aged 18 years old or more with histologic diagnosis was conducted at the Hematology and Oncology Unit of the State University Hospital of Haiti (HUEH) from 2006 to 2015. Variables such as age, gender, year of diagnosis and cancer type were collected. Results: Eight hundred seventy-five cancer cases out of 1191 (73.47%) were selected for this study. The mean age of the study population is 51 years-old [18 – 91] and there were 13.6% males and 86.4% females. Breast cancer is the most common type (70.74% [95% CI, 67.58% - 73.71%]) followed by gastrointestinal cancers (5.6% [95% CI, 4.21% - 7.39%]), leukemias/multiple myeloma (4.69% [95% CI, 3.43% - 6.36%]), skin cancers (4.57% [95% CI, 3.32% - 6.23%]), gynecological cancers (4% [95% CI, 2.84% - 5.58%]), lymphomas (3.77% [95% CI, 2.65% - 5.31%]), sarcomas (3.31% [95% CI, 2.27% - 4.78%]) and ear, nose and throat (ENT) cancers (1.14% [95% CI, 0.58% - 2.16%]). Breast cancer is the most common type among women (80.6%) and the gastrointestinal cancers the most diagnosed among men (21.9%). Conclusions: Breast cancer is by far the most prevalent cancer in this retrospective cohort. Gynecological and lung cancers are underestimated and urology cancers not represented in this sample possibly because they are not systematically referred to the unit.This study can hopefully lead to more advocacy for all patients to be evaluated at the Hematology and Oncology Unit for a better management.