tbuckley/cabot-search huggingface dataset:
Mass Screening for Untreated Atrial Fibrillation
Authors: EmmaSvennberg, JohanEngdahl, FarisAl-Khalili, LeifFriberg, VivekaFrykman, MårtenRosenqvist
Journal: Circulation (2015)

Background—The aims of the present study were to define the prevalence of untreated atrial fibrillation (AF) in a systematic screening program using intermittent ECG recordings among 75- to 76-year-old individuals and to study the feasibility of initiating protective oral anticoagulant (OAC) treatment. Methods and Results—Half of the 75- to 76-year-old population in 2 Swedish regions were invited to a screening program for AF. Participants without a previous diagnosis of AF underwent intermittent ECG recordings over 2 weeks. If AF was detected, participants were offered OAC. During the 28-month inclusion period, 13 331 inhabitants were invited. Of these, 7173 (53.8%) participated. Of the participants, 218 (3.0%; 95% confidence interval [CI], 2.7–3.5) were found to have previously unknown AF, and of these, AF was found in 37 (0.5% of the screened population) on their first ECG. The use of intermittent ECGs increased new AF detection 4-fold. A previous diagnosis of AF was known in 9.3% (n=666; 95% CI, 8.6–1...
Another Option for Hyperhidrosis
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract LB-135: Biomarker utility of the E2/E6 ratio and L1 immunoreactivity for determining HPV16-positive ≥CIN2 lesions and cervical squamous cell carcinoma
Authors: Youn Jin Choi, Sung-Jong Lee
Journal: Cancer Research (2018)

Abstract Objectives: Human papillomavirus (HPV)16 is the most carcinogenic HPV genotype. The objective of this study was to identify whether expression of the HPV16 L1 capsid protein and the E2/E6 ratio—both determined by cervical cytology—could be used as biomarkers of cervical pre-malignancy and cancer. Methods: Cervical specimens were obtained from 226 patients with HPV16 single infection at Seoul St. Mary's Hospital. A Cytoactiv®HPV L1 screening set was prepared to detect the L1 capsid protein, and real-time polymerase chain reaction (PCR) was performed to determine the E2/E6 ratio of HPV16 DNA. Cytology results then were compared to results of conventional histologic analysis of cervical tissues (cervical intraepithelial neoplasia [CIN]1-3 and squamous cell carcinoma [SCC]) to evaluate the association. Results: We found that the mean E2/E6 ratios of specimens graded as SCC (0.355) and of those graded as CIN2/3 (0.481) were significantly lower than the mean E2/E6 ratios for specimens graded as CIN1 (0.736) and those regarded as normal (0.792) (P &amp;lt; 0.05). Cytologic detection of HPV L1 enabled prediction of ≥CIN2 cervical lesions and differentiation of CIN2/3 from SCC (P &amp;lt; 0.05). Based on findings expressed as area under the receiver operating characteristic curve (AUC), the combination of HPV L1 immunohistochemistry and the E2/E6 ratio predicted ≥CIN2 cervical lesions (AUC, 0.871; 95% confidence interval, 0.826-0.917) better than either individual test. Conclusions: To our knowledge, this study is the first to validate the expression of the HPV L1 capsid protein and a decreased HPV E2/E6 ratio as valuable predictive markers of ≥CIN2 cervical lesions, thereby discriminating cervical pre-malignancy and cancer. Cervical cytology can be analyzed on an outpatient basis with noninvasive procedures, in contrast to conventional histologic analysis, which is invasive. Moreover, cervical cytology can be conducted longitudinally to evaluate disease progression/regression without repeated invasive procedures. Citation Format: Youn Jin Choi, Sung-Jong Lee. Biomarker utility of the E2/E6 ratio and L1 immunoreactivity for determining HPV16-positive ≥CIN2 lesions and cervical squamous cell carcinoma [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 LB-135.
Activation of Epithelial Growth Factor Receptor Pathway by Unsaturated Fatty Acids
Authors: NathalieVacaresse, IsabelleLajoie-Mazenc, NathalieAugé, IsabelleSuc, Marie-FrançoiseFrisach, RobertSalvayre, AnneNègre-Salvayre
Journal: Circulation Research (1999)

Abstract—Nonesterified fatty acids (NEFAs) are acutely liberated during lipolysis and are chronically elevated in pathological conditions, such as insulin resistance, hypertension, and obesity, which are known risk factors for atherosclerosis. The purpose of this study was to investigate the effect and mechanism of action of NEFAs on the epithelial growth factor (EGF) receptor (EGFR). In the ECV-304 endothelial cell line, unsaturated fatty acids triggered a time- and dose-dependent tyrosine phosphorylation of EGFR (polyunsaturated fatty acids [PUFAs] were the most active), whereas saturated FAs were inactive. Although less potent than PUFAs, oleic acid (OA) was used because it is prominent in the South European diet and is only slightly oxidizable (thus excluding oxidation derivatives). EGFR is activated by OA independent of any autocrine secretion of EGF or other related mediators. OA-induced EGFR autophosphorylation triggered EGFR signaling pathway activation (as assessed through coimmunoprecipitation o...
A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic Response in Localized and Metastatic Breast Cancer
Authors: Tanya T. Kwan, Aditya Bardia, Laura M. Spring, Anita Giobbie-Hurder, Mark Kalinich, Taronish Dubash, Tilak Sundaresan, Xin Hong, Joseph A. LiCausi, Uyen Ho, Erin J. Silva, Ben S. Wittner, Lecia V. Sequist, Ravi Kapur, David T. Miyamoto, Mehmet Toner, Daniel A. Haber, Shyamala Maheswaran
Journal: Cancer Discovery (2018)

Abstract The multiplicity of new therapies for breast cancer presents a challenge for treatment selection. We describe a 17-gene digital signature of breast circulating tumor cell (CTC)–derived transcripts enriched from blood, enabling high-sensitivity early monitoring of response. In a prospective cohort of localized breast cancer, an elevated CTC score after three cycles of neoadjuvant therapy is associated with residual disease at surgery (P = 0.047). In a second prospective cohort with metastatic breast cancer, baseline CTC score correlates with overall survival (P = 0.02), as does persistent CTC signal after 4 weeks of treatment (P = 0.01). In the subset with estrogen receptor (ER)–positive disease, failure to suppress ER signaling within CTCs after 3 weeks of endocrine therapy predicts early progression (P = 0.008). Drug-refractory ER signaling within CTCs overlaps partially with presence of ESR1 mutations, pointing to diverse mechanisms of acquired endocrine drug resistance. Thus, CTC-derived digital RNA signatures enable noninvasive pharmacodynamic measurements to inform therapy in breast cancer. Significance: Digital analysis of RNA from CTCs interrogates treatment responses of both localized and metastatic breast cancer. Quantifying CTC-derived ER signaling during treatment identifies patients failing to respond to ER suppression despite having functional ESR1. Thus, noninvasive scoring of CTC-RNA signatures may help guide therapeutic choices in localized and advanced breast cancer. Cancer Discov; 8(10); 1286–99. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195
Correlation Between Left Ventricular Hypertrophy and GAA Trinucleotide Repeat Length in Friedreich's Ataxia
Authors: RichardIsnard, HannaKalotka, AlexandraDürr, MireilleCossée, MichèleSchmitt, FrançoisePousset, DanielThomas, AlexisBrice, MichelKoenig, MichelKomajda
Journal: Circulation (1997)

Background Friedreich's ataxia (FA), the most common inherited ataxia, is associated frequently with cardiac hypertrophy, and death is often cardiac related. Recently, the disease has been associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9. Methods and Results We studied 44 consecutive patients with FA, determined the size of GAA expansions in the frataxin gene, and examined the relation between the genotype and cardiac phenotype assessed by M-mode and two-dimensional echocardiography. All the patients were homozygous for the mutation. The size of the GAA expansion on the smaller allele varied from 270 to 1200. We found a correlation between the size of GAA expansion and the left ventricular wall thickness (r=.51, P<.001) and the left ventricular mass index (r=.45, P=.002). Left ventricular hypertrophy was observed in 81% of patients with a number of GAA repeats above the median value of 770 compared with only ...
Prognostic Value of Ambulatory and Home Blood Pressures Compared With Office Blood Pressure in the General Population
Authors: RobertoSega, RitaFacchetti, MicheleBombelli, GiancarloCesana, GiovanniCorrao, GuidoGrassi, GiuseppeMancia
Journal: Circulation (2005)

Background— Studies in hypertensive patients suggest that ambulatory blood pressure (BP) is prognostically superior to office BP. Much less information is available in the general population, however. Obtaining this information was the purpose of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Methods and Results— Office, home, and 24-hour ambulatory BP values were obtained in 2051 subjects between 25 and 74 years of age who were representative of the general population of Monza (Milan, Italy). Subjects were followed up for an average of 131 months, during which time cardiovascular and noncardiovascular fatal events were recorded (n=186). Office, home, and ambulatory BP values showed a significant exponential direct relationship with risk of cardiovascular or all-cause death. The goodness of fit of the relationship was greater for systolic than for diastolic BP and for night than for day BP, but its overall value was not better for home or ambulatory than for office BP. The slope of...
Abstract 2898: Inhibition of HDAC6 as a novel targeted therapy in breast cancer
Authors: Tizita Z. Zeleke, Preeti Putcha, Jiyang Yu, Andrea Califano, Jose M. Silva
Journal: Cancer Research (2018)

Abstract The identification and use of biomarkers is critical to guided clinical care. Cancer treatment has made use of many biomarkers to determine which therapeutic avenues are adequate for each patient. For example, the use of Trastuzumab is intimately linked to the presence of HER2/NEU amplification in breast cancers. Previous work from our group established the importance of HDAC6 in maintaining the homeostasis of inflammatory breast cancer cells (IBC). We also reconstructed the HDAC6 regulon using gene expression profile signatures from over 900 primary breast cancers to obtain a biomarker that guide the use of HDAC6 inhibitors towards the right patient group. This method identified a regulon of 162 transcripts as a set of transcriptional targets whose expression is affected by HDAC6 master regulator activity. Finally, the expression of all transcripts that are co-regulated by HDAC6 in the breast cancer samples were integrated into a single score termed as the HDAC6 score. Through this work, we established that HDAC6 score is associated with cancer cell response to HDAC6 inhibitor ACY1215. HDAC6, one of eighteen deactylases, is distinct from all other HDACs as it is located mainly in the cytosol and has non-chromatin substrates such as α-tubulin and HSP90. HDAC6 inhibitors have gained a lot of momentum in the clinic for hematological malignancies and our computational analysis has also revealed that these tumors also exhibit a high HDAC6 score. Therefore, by identifying the HDAC6 score for tumors, we can widen the scope of using HDAC6 inhibitors to a wide range of cancers. Our increasing understanding of tumor biology has led to the use of combinatorial therapies to fully benefit from cancer therapy. This project will encompass the use of combinatorial therapy containing HDAC6 inhibitors and paclitaxel to demonstrate an increased potential in treating breast cancer. These studies will closely mirror the clinical trial that we are undertaking with our collaborators from Acetylon where metastatic breast cancer patients are being treated using HDAC6 inhibitor ACY1215 in combination with nab-paclitaxel (NCT02632071). This project aims to provide the frame work to utilize for the first time the HDAC6 score as a marker for identifying tumors that will be most susceptible to HDAC6 inhibition in the clinic. Citation Format: Tizita Z. Zeleke, Preeti Putcha, Jiyang Yu, Andrea Califano, Jose M. Silva. Inhibition of HDAC6 as a novel targeted therapy in breast cancer [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 2898.
Abstract 335: Variable off-target effects of clinically advanced PARP inhibitors
Authors: Monica E. Wielgos, Jay Patibandla, Michelle Firlit, Elke Van Oudenhove, Paulina Cybulska, Petar Jelinic, Douglas A. Levine
Journal: Cancer Research (2018)

Abstract High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with low 5-year survival rates. Inhibitors of poly (ADP-ribose) polymerase (PARP) are promising novel agents that uniquely target HGSOCs with DNA repair deficiencies. The majority of patients with DNA repair proficient HGSOCs do not respond to PARP inhibitor monotherapy, highlighting the need for novel treatment approaches for these women. The goal of this study was to expand the patient population that could benefit from PARP inhibition by identifying the off-target effects that are favorable in combination with CHK1 inhibitors among the five most clinically advanced PARP inhibitors. Cell cycle and western blot analysis revealed that the four most potent PARP trappers (rucaparib, olaparib, niraparib, and talazoparib) have a strong effect on the cell cycle. The PARP trappers in particular activated CHK1 through phosphorylation at the serine 345 residue, decreased total protein levels of CDC25C, and arrested cells in the S/G2 phase of the cell cycle. These results were not observed after treatment with veliparib, the least potent PARP trapper. We created phospo-CHK1 mutants to confirm CHK1 activation at serine 345 and to further investigate whether potent PARP trappers activate CHK1 on serine 317, another residue that is also phosphorylated in response to replication stress. The data suggest that PARP trappers activate CHK1 at both the serine 317 and 345 phosphorylation sites. Next, we examined whether PARP inhibition-induced activation of CHK1 is a determinant of synergy between PARP and CHK1 inhibitors. We exposed one of our established BRCA wild-type, TP53 mutant HGSOC patient-derived xenograft models to a PARP1 inhibitor (veliparib or talazoparib) or to the CHK1 inhibitor (MK-8776) or a combination of PARP and CHK1 inhibitors. CHK1 inhibition slightly increased sensitivity to talazoparib compared to single agent therapy. However, the tumor volume was significantly reduced by the combination of CHK1 inhibition and veliparib treatment compared to either single agent alone. This study suggests that there are off-target cell cycle effects that vary among the five most clinically-advanced PARP inhibitors that likely influence the response to combinatorial treatment. We propose the use of PARP and CHK1 inhibition as a strategy for HGSOC patients who would otherwise have minimal benefit to PARP inhibitor monotherapy. Citation Format: Monica E. Wielgos, Jay Patibandla, Michelle Firlit, Elke Van Oudenhove, Paulina Cybulska, Petar Jelinic, Douglas A. Levine. Variable off-target effects of clinically advanced PARP inhibitors [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 335.
Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction
Authors: GabrielArefalk, KristinaHambraeus, LarsLind, KarlMichaëlsson, BertilLindahl, JohanSundström
Journal: Circulation (2014)

Background—Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results—All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7–16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8–23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (haz...
Abstract 1848: A comprehensive image cytometry method to identify and functionally characterize a rare subpopulation of platinum-induced aneuploid tumor cells in high-grade serous carcinoma
Authors: Yu Wing Yeung, Oliver Fung, Mikhail Bashkurov, Robert Rottapel, Andras Kapus
Journal: Cancer Research (2018)

Abstract Background: Although platinum treatment effectively reduces tumor bulk for high grade serous carcinomas of tubal-ovarian origin, there are often scattered tumor cells exhibiting reparative and aneuploid features that remained within the peritoneal cavity. The biological importance of these aneuploid cells has not been well elucidated. In this study, we used HGSC cell line models and developed an improved image cytometry approach to identify these aneuploid cells for functional interrogation. Methods: We have developed a comprehensive image cytometry approach to assess DNA ploidy and cell cycle phase distribution within a standard flow cytometry software platform and validated this methodology using phase-specific markers (EdU, pRb, Geminin, pH3). We further introduced a novel ‘brightness vs. nuclear size' scatter plot to enhance the cell cycle assessment at the single-nucleus level. The method was applied to correlate the kinetics of the DNA damage and checkpoint response with the cell cycle status and cell viability on HGSC cell lines (OVCAR3, TOV3133G) after in-vitro carboplatin treatment. Results: Using this improved image cytometry method, we identified the emergence of a rare subpopulation of large aneuploid tumor cells at 1 week after platinum treatment. These large aneuploid cells remained viable (PI- and cleaved-PARP negative) but were uniquely dependent on anti-apoptotic signaling for their continual survival. While the bulk population of treated tumor cells underwent mitotic catastrophe following premature G2-M checkpoint exit, a rare subpopulation escaped cell death likely via mitotic slippage as they exhibit characteristic features of aneuploidy. These large aneuploid cells remained KI-67 positive and clonal dilutional experiments are being performed to assess their regrowth potential. Conclusions: This study has identified a rare subpopulation of tumor cells that avoided mitotic cell death after platinum treatment and then survived in an aneuploid state. The derivation of aneuploid cells via mitotic slippage subsequent to platinum treatment is an under-recognized phenomenon but may pose as an important drug-resistant mechanism due to enhanced survival strategies co-opted by these aneuploid cells. Research funding: Ontario Institute for Cancer Research Citation Format: Yu Wing Yeung, Oliver Fung, Mikhail Bashkurov, Robert Rottapel, Andras Kapus. A comprehensive image cytometry method to identify and functionally characterize a rare subpopulation of platinum-induced aneuploid tumor cells in high-grade serous carcinoma [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 1848.
Abstract 1056: Cancer avatars are sensitive diagnosticians of the pleural space
Authors: Gwendolyn B. Kuzmishin, Priyanka Gopal, Mohamed E. Abazeed
Journal: Cancer Research (2018)

Abstract The identification of malignant cells in pleural fluid has critical prognostic and therapeutic implications but is frequently a diagnostic challenge. The first step in determining the cause of a suspected malignant pleural effusion, thoracentesis, has an unsatisfying low sensitivity (~60-70%). Patient-derived xenografts (PDX) retain the principal characteristics of the tumor of origin. However, there has been little progress in the application of these models to guide diagnostic and staging strategies. We assessed the feasibility, cellular yield and comparative diagnostic accuracy of pleural-derived xenografts in patients with effusions. An institutional review board-approved single-institution prospective registry of patients was used to identify patients undergoing diagnostic and/or therapeutic thoracentesis. Cells isolated from the pleural fluid of these patients were injected into NSG mice. A diagnosis of the cancer in the xenograft was confirmed by a staff pathologist with expertise in the correspondent cancer type. All of the cases that were clinically positive for tumor cells in the pleural space demonstrated tumor engraftment. Samples taken from patients with known benign etiologies did not result in tumor engraftment. The developed xenografts provided ample tissue that can be made available for extensive molecular testing, even in cases where the cytological samples consisted of very few cells. Critically, two of 10 cases resulted in engraftment of the tumor despite no evidence of malignant cells on cytological examination, indicating a 20% improvement in the statistical power of pleural-based xenografting for the detection of malignancy. Our study indicates that pleural-derived xenografts can enhance the sensitivity of malignant cell detection, reflecting the inherent limitations of cytological analyses of a few malignant cells. Moreover, the amplification of cellular material provides ample source material that can be used to satisfy the increasing demands for tissue-based molecular testing. To our knowledge, this is the first effort to effectively use patient-derived xenografts for the purpose of cancer staging and diagnosis. Citation Format: Gwendolyn B. Kuzmishin, Priyanka Gopal, Mohamed E. Abazeed. Cancer avatars are sensitive diagnosticians of the pleural space [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 1056.