tbuckley/cabot-search huggingface dataset:
Detection of Activating Estrogen Receptor Gene (<i>ESR1</i>) Mutations in Single Circulating Tumor Cells
Authors: Carmela Paolillo, Zhaomei Mu, Giovanna Rossi, Matthew J. Schiewer, Thomas Nguyen, Laura Austin, Ettore Capoluongo, Karen Knudsen, Massimo Cristofanilli, Paolo Fortina
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and Sanger sequencing. Results: Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two different ESR1 variants in a single CTC and another showed loss of heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). Furthermore, one had 2 serial blood samples analyzed and showed changes in both cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has not been reported previously. Conclusions: CTCs are easily accessible biomarkers to monitor and better personalize management of patients with previously demonstrated ER-MBC who are progressing on endocrine therapy. We showed that single CTC analysis can yield important information on clonal heterogeneity and can be a source of discovery of novel and potential driver mutations. Finally, we also validate a workflow for liquid biopsy that will facilitate early detection of ESR1 mutations, the emergence of endocrine resistance and the choice of further target therapy. Clin Cancer Res; 23(20); 6086–93. ©2017 AACR.
A Fusion Receptor as a Safety Switch, Detection, and Purification Biomarker for Adoptive Transferred T Cells
Authors: Xiuqi Wu, Bizhi Shi, Jiqin Zhang, Zhimin Shi, Shengmeng Di, Minliang Fan, Huiping Gao, Hai Wang, Jianren Gu, Hua Jiang, Zonghai Li
Journal: Molecular Therapy (2017)
Abstract 15214: Geometry No Longer Matters - Sphericity Index No Longer Predicts Aortic Regurgitation With SAPIEN 3 TAVR
Authors: Giorgio A Medranda, Paul Sapia, Zack Williams, Kunal Brahmbhatt, Rose Calixte, Richard Schwartz, Kevin Marzo, Beevash Ray, Juan Gaztanaga, Stephen Green
Journal: Circulation (2016)

Introduction:  Despite the advent of the third generation transcatheter aortic valve replacement (TAVR) device, aortic regurgitation (AR) continues to be a known complication with significant impact on morbidity and mortality. We have evaluated our sphericity index (SI) for predicting development of significant AR post-TAVR in first and second generation TAVR devices.   Hypothesis:  We hypothesize that the degree of circularity of the aortic annulus on pre-TAVR multi detector computed tomography (MDCT) predicts development of post-TAVR significant AR in the third generation TAVR device.   Methods:  This was an observational, retrospective study, in which we reviewed data on 224 intermediate risk patients who underwent TAVR using the Edwards SAPIEN 3 valve at our institution from 2013-2016. Using MDCT, aortic annulus measurements were collected to calculate SI. SI was calculated by dividing the long diameter by the short diameter of the aortic annulus. Using the previous SI cutoff of 1.33 (corresponding to a 33% deviation from a circle), we used Fisher’s exact test on the third generation TAVR device in predicting development of significant AR post-TAVR. Significant AR was defined as moderate or severe AR. Pre-discharge transthoracic echocardiograms (TTEs) were used to determine degree of AR. All analyses were done using SAS 9.4® with a p-value    Results:  The 224 patients had a mean age of 82.4 ± 7.7 years, mean BMI of 28.9 ± 6.5 kg/m 2 , were 96.9% non-Hispanic Caucasian and 52.2% male. The mean SI was 1.25. In this population, there were 19.2% of patients who had an SI > 1.33. There were 3.1% of patients who developed significant AR of which all were paravalvular. There were 3.3% of patients with an SI of 1.33 or less who developed significant AR post-TAVR and 2.3% of patients with an SI above 1.33 who developed significant AR post-TAVR (p = 0.999).   Conclusions:  We have determined that the SI, previously predictive of significant AR in first and second generation TAVR devices, is not predictive of development of significant AR in the Edwards SAPIEN 3 valve. We hypothesize that technical advancements, including the outer sealing skirt, prevent paravalvular AR regardless of pre-TAVR aortic annulus geometry.
Persistent cough: A question for the gastroenterologist?
Authors: Elizabeth Parsons, Bronwen E Warner, Barbara Braden
Journal: Gut (2017)

An 80-year-old female retired teacher was admitted under the medical team with right-lower-lobe pneumonia.

The patient, a non-smoker with minimal alcohol intake, had a medical history of non-Hodgkin’s lymphoma treated with radiotherapy and splenectomy 30 years before, Barrett’s oesophagus (C9M9 Prague Classification) with distal oesophageal ulcer diagnosed 8 months previously, hiatus hernia and dual-chamber pacemaker for sinus-arrest. Medications were omeprazole 80 mg and ranitidine 300 mg daily.

During the preceding two years, the patient had consulted Respiratory and Gastroenterology teams for a persistent cough worsened by eating and drinking and two stone weight loss (admission BMI 16). High-resolution CT demonstrated subsegmental atelectasis and ground glass changes in …
Major Bleeding in Patients With Diabetes and Atrial Fibrillation Treated With New Oral Anticoagulants—Reply
Authors: Anna Plitt, Darren K. McGuire, Robert P. Giugliano
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
FRI0036 Population pharmacokinetics (pk) of anakinra in subjects with rheumatoid arthritis (ra)
Authors: B Yang, J Frazier, D McCabe, JD Young
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Anakinra is a recombinant interleukin-1 receptor antagonist that reduces signs and symptoms and slows joint destruction in RA patients in clinical trials. Population PK analysis was conducted on data from RA patients treated with anakinra. <h3>Objectives</h3> The objective was to investigate the effect of covariates such as creatinine clearance (CLcr), body weight (WT), age, and sex, on anakinra PK. <h3>Methods</h3> Subjects (n = 341) received daily SC injections of anakinra at 30, 75, or 150 mg for 6 months; one plasma sample for anakinra measurement was collected from each subject at baseline, and at weeks 1, 4, 12, 20, and 24 before anakinra administration for that day. Plasma samples were analysed for anakinra levels by an ELISA method. Plasma anakinra data were analysed by nonlinear mixed-effects modelling using NONMEM. "Population" mean PK parameters, intersubject variability in the PK parameters, and residual error were estimated. <h3>Results</h3> Anakinra PK appeared to be dose independent and was adequately described by a one-compartment model with first-order absorption and elimination. Results showed that anakinra volume of distribution (Vd/F) increased linearly with increasing WT (Vd/F = 0.142 * WT, p &lt; 0.05). Both CLcr and WT were significant predictors of anakinra plasma clearance (CL/F); clearance increased with increasing CLcr and WT (CL/F = 23.0 + 0.343 * CLcr + 0.713 * WT, p &lt; 0.05). The plasma clearance of anakinra was higher in men (164 ± 25 mL/min, n = 79) than in women (144 ± 22 mL/min, n = 262) and higher in younger subjects (&lt; 65 yr, 152 ± 24 mL/min, n = 262) than in older subjects (&gt; 65 yr, 138 ± 23 mL/min, n = 79), these differences could be explained by differences in CLcr and WT. <h3>Conclusion</h3> Results from population PK analyses confirmed nonclincial and clinical data, which showed the kidney to be a major clearance organ for anakinra.
Thailand experiences on cervical cancer prevention using vinegar.
Authors: Khunying Kobchitt Limpaphayom, Wachara Eamratsameekool, Bandit Chumworathayi
Journal: Journal of Clinical Oncology (2014)

1517 Background: Cervicare Thailand is a visual inspection using acetic acid(VIA)and cryotherapy in a single visit approach(SVA) project that was initiated by Jhpiego,an affiliate of the Johns Hopkins University, and funded by Bill and Melinda Gates Foundation. Since 2002 the program has been supported locally. Purpose of this paper is to report of the results of scale up of the cervical cancer prevention initiative. Methods: The cervical cancer screening and treatment data were retrieved from service statistics that were routinely report in national health information system.We focused our data capture and analysis on 34 provinces where SVA is available. Additionally we utilized reports of training to supplement our data review. Results: Since 2000, there were 63 courses for SVA resulted in 1388 nurses qualified provide SVA in 34 of 77 provinces across Thailand. Another 149 clinical trainers were prepared to assist in training more providers and also conduct supportive supervision .Up to December 2013,749,407(22.8%)from a total of 3,285,585 women aged 30-45 have been screened with VIA. Positive VIA result were found in 27,978(3.7%) of which 15,396(55.0%) received treatment with cryotherapy at the same visit. The number of VIA positive cases referred for additional care was 12,582(45%).The referral were gynecologic problem and/or lesion ineligible for cryotherapy. Another 9,101(1.2%) women had suspicious cervical cancer finding, which required further diagnosis and treatment. Conclusions: SVA can be provided and made sustainable in Thailand. This approach increased accessibility and addresses health inequity for women in remote area.The scaled up has also identified the challenges and issue attendant to scaling up as well as the key lesson learned in improving the cervical cancer prevention in Thailand. While impact has yet to be measured nationally, the report from one of the province is promising. Roi-et where they have fully scaled up SVA, hospital based cancer registry show a declining trend for invasive cervical cancer year 2006 and 2011, reporting a drop from 65 cases to 54 cases.
A clinical validation study of RASKET-B: A multiple detection kit for RAS and BRAF gene mutations in colorectal cancer
Authors: Takeshi Kajiwara, Tomohiro Nishina, Hiroya Taniguchi, Kei Muro, Kiwamu Akagi, Hiroki Hara, Tadamichi Denda, Shuichi Hironaka, Toshihiro Kudo, Taroh Satoh, Wataru Okamoto, Takayuki Yoshino
Journal: Annals of Oncology (2017)
Hepatocyte growth factor (HGF) binding domains on fibronectin and vitronectin promote enhanced endothelial cell migration via a specific ras and PI3-kinase dependent pathway.
Authors: K Patel, E S Wijelath, Yatin Patel, R Sumathipala, M S Sobel, J Murray, J Seago, Geoffrey Savidge, Salman Rahman
Journal: Blood (2003)
Clonal Immunoglobulin λ Light-Chain Gene Rearrangements Detected By Next Generation Sequencing in POEMS Syndrome
Authors: Chika Kawajiri-Manako, Naoya Mimura, Masaki Fukuyo, Hiroe Namba-Fukuyo, Bahityar Rahmutulla, Yuhei Nagao, Emi Togasaki, Ryoh Shimizu, Nagisa Hasegawa, Shio Sakai, Yusuke Takeda, Chikako Ohwada, Masahiro Takeuchi, Emiko Sakaida, Tohru Iseki, Sonoko Misawa, Koutaro Yokote, Makoto Tsuiji, Satoshi Kuwabara, Atsushi Kaneda, Chiaki Nakaseko
Journal: Blood (2016)
Malignancy following lung transplantation.
Authors: Ammar Khanshour, Raed Abu Awwad, Robert Chapman, Alan Betensley
Journal: Journal of Clinical Oncology (2012)

e12019 Background: Malignancy has been shown to be a frequent complication of solid organ transplantation. It has been reported more commonly in lung transplant patients compared to other solid organ transplant recipients presumably due to the greater degree of immunosuppression required for these patients; the International Society for Heart and Lung Transplantation (ISHLT) reported that malignancies account for 15% of all deaths of lung transplant patients between 5 and 10 years after transplant. The aim of this study is to describe malignancies observed in patients who underwent lung transplantation in a single, large tertiary center. Methods: A retrospective analysis of the medical records of all adult recipients of lung allografts transplanted at Henry Ford Hospital between 1994 and 2010 was performed. Main variables included age at transplant, type of transplant, smoking status and type of malignancy. Study end point was development of malignancy. Patients surviving less than 3 months were excluded from the final analysis. T-test and Chi-square tests were used in the statistical analysis. Results: 145 patients received lung transplants with 136 patients surviving at least 3 months. Of the 136 cases included; 31 (23%) patients developed post-transplant malignancy as follows: skin cancer in 17, lung cancer (in the native lung) in 10, colon cancer in 3, cervical cancer in 3, renal cell carcinoma in 2, post transplant lymphoproliferative disorder (PTLD) in 2, head and neck cancer in 2, bladder cancer in 1 and vulvar cancer in 1. Eight patients developed more than one malignancy. 83% of those who developed malignancy were smokers while 67% of those who did not develop malignancy were smokers (Chi-square is 3.41, P&gt;0.05). Patients who developed malignancy were older at time of transplantation (mean ± SD, 58.0±7.5 vs. 55.6±9.0 years; P= 0.04). Conclusions: Malignancy is a common complication after lung transplantation, with skin cancer being the most common. Age at transplantation seems to be a risk factor for development of malignancy. Smoking as a risk factor did not reach statistical significance in the studied population.
AG-024322 is a multi-targeted CDK inhibitor with potent antitumor activity in vivo
Authors: Cathy C. Zhang, Gabriel Troche, Zhengming Yan, Maria E. Arango, Joseph Higgins, David Romero, Susan Kephart, Indrawan McAlpine, Tatiana Koudriakova, Judith Skaptason, Jim Nonomiya, Daniel Knighton, Rose Ann Ferre, Jayashree Tikhe, Gennady Verkhivker, Meirong Xu, William Romines, Cindy Palmer, Julie Park, Siegfried Reich, Gerrit Los, Cristina Lewis
Journal: Cancer Research (2005)

4413  Deregulated cyclin-dependent kinase (CDK) activity is characterized by uncontrolled cell cycle progression, which is a hallmark of human cancer. AG-024322 is a multi-targeted (pan)-CDK inhibitor displaying potent inhibition of the cell cycle kinases CDK1, CDK2, and CDK4. In cellular assays AG-024322 inhibits phosphorylation of CDK substrates, causing induction of cell cycle arrest, broad-spectrum anti-proliferative activity and induction of apoptosis. In vivo experiments demonstrate that AG-024322 inhibits the growth of established human tumor xenografts of different origins. Significant anti-tumor efficacy was observed in 8 of the 9 tumor models tested, with tumor growth inhibition (TGI) ranging from 32% to 86.4%. In addition, the anti-tumor effects of AG-024322 are dose-dependent. At the maximum tolerated dose (MTD) of 20 mg/kg, AG-024322 causes a 65% TGI in the MV522 tumor model, 52% TGI at 1/2 of the MTD and only slight anti-tumor activity at 1/4 of the MTD. Direct evidence that AG-024322 antitumor activity correlates with modulation of the target was obtained by monitoring the phosphorylation status of the substrate Retinoblastoma (Rb) protein in tumor tissue. There is a clear dose dependent reduction in the level of phospho-Rb795, and this inhibition of Rb phosphorylation in vivo shows a strong correlation with the dose-dependent inhibition of tumor growth. In addition, treatment with AG-024322 causes dose-dependent apoptosis in tumors in vivo, as assessed by TUNEL staining of the excised tumors. Similarly, staining for Ki67, a common marker of cell proliferation, is significantly reduced after administration of AG-02322 at MTD levels. The sum of the in vivo data demonstrates that AG-024322 displays broad-spectrum anti-tumor activity and clear target modulation in vivo, as demonstrated by inhibition of Rb phosphorylation, anti-proliferative staining, and induction of apoptosis. Moreover, the extent of target modulation correlates with drug exposure in the pharmacodynamic model.
The workload and impact of a dedicated cancer of unknown primary (CUP) service on patients with imaging suggestive of metastatic disease
Authors: Alistair Mclaren, Danny Ulahannan, Emily Keen, Grant Stewart, James Bell, Katie Planche, Niall Power, Shaunak Navalkissoor, Rachel Craig, TuVinh Luong, Jennifer Watkins, Ian Clark, Roopinder Gillmore
Journal: Annals of Oncology (2017)
Large outbreak of urogenital schistosomiasis acquired in Southern Corsica, France: monitoring early signs of endemicization?
Authors: H. Noël, M. Ruello, A. Maccary, C. Pelat, C. Sommen, J. Boissier, H. Barré-Cardi, J. Fillaux, J.-L. Termignon, M. Debruyne, G. Chyderiotis, J. Durand, L. Ramalli, J.-D. Chiappini, P. Malfait, A. Berry
Journal: Clinical Microbiology and Infection (2017)
Abstract 78: TNFR2 Stimulation Promotes Mitochondrial Fusion via Stat3 and NF-kB Dependent Activation of OPA1 Expression
Authors: Jing-Liang Nan, Wei Zhu, Ying-Chao Wang, Zhi-Wei Zhong, Lian-lian Zhu, Yan Wu, Jing Zhao, Jing-Hai Chen, Xin-Yang Hu, Hong Yu, Mahesh Gupta, Jian'an Wang
Journal: Circulation Research (2016)

Background: TNFR2 stimulation is known to possess protective effects for the cardiomyocytes, however, the underlying mechanisms remain unknown. Methods and Results: Using cultured neonatal cardiomyocytes that were infected with lentivirus containing shRNA targeting TNFR1, we showed that TNFR2 activation by TNFα (5nmol/L) resulted in increased mitochondrial fusion, mitochondrial membrane potential which were associated with both elevated intracellular ATP levels and oxygen consumption rate. Intriguingly, these changes were associated with increased protein levels of OPA1, with no changes in the expression levels of Drp1, Mfn1, Mfn2. We went further and reproduced previously reported data that NF-kB acetylation (Lys310) was increased with TNFR2 activation. Interestingly, however, we also observed dose-dependent effects on increase in Stat3 acetylation. Using shRNA approach, we then demonstrated that either Stat3 or NF-kB knockdown can attenuate TNFR2 induced OPA1 expression. The close interaction between these two signalings was validated by co-IP assay and confocal immunofluorescence staining. Aided by bio-informatics searching, we then performed ChIP assay to show that the binding sites of OPA1 promoter regions for STAT3 (-156 to -167) and NFkB (-192 to -203) were adjacent. We further validated that p300 induced Stat3 acetylation was indispensable for complex formation by the interaction between Stat3-DBD and NF-kB -ΔRHD, which in turn was a key event for OPA1 transcription activation. And silence of p300 can abolish OPA1 upregulation upon TNFR2 activation. Computerized data analysis based on zdock and zrank score followed by molecular dynamic simulation model for the whole Stat3 structure revealed higher value of the exterior dielectric constant (obtained from MM/PBSA calculation) for the two sites, K370 and K383, of Stat3, suggesting the essential roles for these two sites for Stat3-NFkB interaction, which were confirmed by co-IP with Stat3-DBD mutants (K370Q,K370R,K383Q,K383R) approach. Conclusions: Our data suggested that p300 mediated Stat3 acetylation cooperates with NF-kB to modulate TNFR2 activation induced OPA1 upregulation, leading to improved mitochondrial morphology and function.
NORDIC HAMSTRING EXERCISE STRENGTH CHANGES OVER A SEASON IN ACADEMY FOOTBALLERS
Authors: Sam Huggins, Nicholas Davies, Kate Evans, Morgan Williams
Journal: British Journal of Sports Medicine (2017)

Background The Nordic hamstring exercise (NHE) has been utilised within Hamstring Strain Injury prevention programmes. However, there is a concern amongst some that once a football season has commenced, there is insufficient time to include the NHE due to short turn around between matches. To date, changes in strength have not been documented over a season. Objective To determine if changes in strength measured during the NHE using a commercially available device can occur as the season progresses. Design Time series design that involved measures of Nordic exercise strength (NES) obtained throughout the 2015–2016 season whist undertaking a hamstring strengthening intervention. Setting Professional Football Academy. Patients (or Participants) 33 male football academy players aged between 16 and 21 years. Interventions (or Assessment of Risk Factors) One session of 2 sets 3–6reps NHE in addition to normal posterior chain strengthening exercises weekly. Main Outcome Measurements NES (mean of left and right limbs) and between limb difference (%) were analysed by phase of the season (i.e., pre-season pre-Christmas, post-Christmas and end of season periods). Results At pre-season the NES and between limb difference baseline data was 337±68N and 9±6%. Increases were observed in NES from pre-season to pre-Christmas (16N, P=0.0126) and post-Christmas to end of the season (15N, P=0.0180). Over the Christmas period the increase was smaller (5N, P=0.3871). The between limb scores, however, remained stable (P=0.6010). Post-hoc analysis revealed a negative association (r=-0.65) between preseason NES and the change in NES from baseline to end of the preseason. Conclusions Most players increased their NES over the season, yet imbalance between limbs remaining stable throughout. Stronger players of the squad at the start of pre-season did not improve as much as their weaker colleagues. The weekly low volume stimulus may offer an adequate stimulus to develop strength.
Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial
Authors: David Z I Cherney, Bernard Zinman, Silvio E Inzucchi, Audrey Koitka-Weber, Michaela Mattheus, Maximilian von Eynatten, Christoph Wanner
Journal: The Lancet Diabetes & Endocrinology (2017)