tbuckley/cabot-search huggingface dataset:
Genome-wide plasma DNA methylation features of metastatic prostate cancer
Authors: Anjui Wu, Paolo Cremaschi, Daniel Wetterskog, Vincenza Conteduca, Gian Marco Franceschini, Dimitrios Kleftogiannis, Anuradha Jayaram, Shahneen Sandhu, Stephen Q. Wong, Matteo Benelli, Samanta Salvi, Giorgia Gurioli, Andrew Feber, Mariana Buongermino Pereira, Anna Maria Wingate, Enrique Gonzalez-Billalebeitia, Ugo De Giorgi, Francesca Demichelis, Stefano Lise, Gerhardt Attard
Journal: Journal of Clinical Investigation (2020)

Tumor DNA circulates in the plasma of cancer patients admixed with DNA from noncancerous cells. The genomic landscape of plasma DNA has been characterized in metastatic castration-resistant prostate cancer (mCRPC) but the plasma methylome has not been extensively explored. Here, we performed next-generation sequencing (NGS) on plasma DNA with and without bisulfite treatment from mCRPC patients receiving either abiraterone or enzalutamide in the pre- or post-chemotherapy setting. Principal component analysis on the mCRPC plasma methylome indicated that the main contributor to methylation variance (principal component one, or PC1) was strongly correlated with genomically determined tumor fraction (r = –0.96; P < 10–8) and characterized by hypermethylation of targets of the polycomb repressor complex 2 components. Further deconvolution of the PC1 top-correlated segments revealed that these segments are comprised of methylation patterns specific to either prostate cancer or prostate normal epithelium. To extract information specific to an individual's cancer, we then focused on an orthogonal methylation signature, which revealed enrichment for androgen receptor binding sequences and hypomethylation of these segments associated with AR copy number gain. Individuals harboring this methylation pattern had a more aggressive clinical course. Plasma methylome analysis can accurately quantitate tumor fraction and identify distinct biologically relevant mCRPC phenotypes.
Using qualitative data to examine disparities in cancer outcomes: Results from interviews with African American (AA) and white (W) patients regarding health beliefs and perceptions of chemotherapy
Authors: B. N. Polite, S. Gehlert, F. Hlubocky, D. Smith, C. K. Daugherty
Journal: Journal of Clinical Oncology (2006)

16016 Background: Prior data indicate African Americans are less likely to receive appropriate and timely therapy for breast, colon, and lung cancers. The reasons for this may involve differences in how AA patients (pts) perceive the risks and benefits of available therapies. In general, little is known about the beliefs of pts, and about AA’s in particular, toward the risks and benefits of chemotherapy. Methods: Semi-structured qualitative interviews are being conducted on pts who have been referred to receive chemotherapy for breast, colon, and lung cancer. Results: To date, 18 patients have been interviewed: 9AA, 9W; median age 61 (range 35–77); 11 lung, 4 breast, 3 colon (11 for adjuvant therapy and 7 with metastatic disease). Pts provided their beliefs on the role of chemotherapy. Many described the advantages of chemotherapy indicating the possibility of cure or remission. Others expressed a degree of skepticism about the curative intent of chemotherapy. Many indicated an expectation of moderate to severe side effects that may have lasting effects on the body. Trust in one’s physician and the role of religion/spirituality are also emerging themes. One AA pt described that chemotherapy was a way for physicians to experiment on patients. Others believed that trust in one’s physician was implicit and essential. Many indicated a belief in God but few believed that his/her religious beliefs affected his/her approach to treatment. Conclusions: Consistent with the health beliefs’ model, perceived benefits and perceived barriers (one’s belief about the tangible and psychological costs of the advised action) shape pts’ perceptions of chemotherapy. In this ongoing analysis, the perceived benefits are tempered by a degree of skepticism. The perceived barriers include concerns about the overall impact of chemotherapy on the body and spirit rather than specific short-term side effects. Also, belief in the use of chemotherapy as an experiment is potentially consistent with some African American patients’ perceptions. No significant financial relationships to disclose.
Liquid biopsy-based assays to monitor residual disease in cancer.
Authors: Gangwu Mei, Dragan Sebisanovic, Alain Mir, Zulfiqar Gulzar, James D. Brooks, Stefanie S. Jeffrey, AmirAli Talasaz
Journal: Journal of Clinical Oncology (2013)

11096 Background: One of the main challenges in cancer management is monitoring the non-organ-confined disease post metastasis. Recently analysis of circulating tumor nucleic acids has generated a new paradigm for monitoring the progression and molecular pathology of the residual disease through a non-invasive test. Methods: We have developed a new sequencing workflow, which increases the sensitivity and specificity of detecting and quantifying rare tumor-derived nucleic acids among healthy fragments by at least ten-fold. Unlike conventional sequencing library preparation protocols, the majority of extracted circulating DNA fragments are hybridized to sequencing flow cells with minimal modifications. The sequencing data are processed using our proprietary bioinformatics pipelines to search for rare genetic abnormalities within the heterogeneous circulating fragments. Results: To study the performance of our technology, we first evaluated its sensitivity in analytical samples. We spiked varying amounts of LNCaP cancer cell line gDNA into a background of normal gDNA and were able to successfully detect somatic mutations down to 0.1% sensitivity. Subsequently, we investigated the correlation of circulating DNA and tumor gDNA in human xenograft models in mice. In seven different mice models of two different human tumors, we found very strong correlation between somatic mutations detected in all pairs of tumor gDNA and mouse blood cfDNA. After preclinical studies, we initiated a pilot study on human samples across different cancer types. We found more than 90% correlation between tumor mutations in stage IIIb CRC cancer patients and the mutations detected in their circulation (n=7). In a pilot study in prostate cancer patients (n=3), we detected chromosomal abnormalities in multi locations in circulating DNA genome in both advanced and post-relapse stages of the disease. Conclusions: The present work indicates the potential of using circulating nucleic acids to facilitate the integration of real-time molecular pathology into routine cancer care. Our assay will be used to identify residual disease after neoadjuvant chemotherapy and/or surgery, but may also identify a subset of patients who may benefit from alternative therapies.
Preliminary activity of AMN107, a novel potent oral selective Bcr-Abl tyrosine kinase inhibitor, in newly diagnosed Philadelphia chromosome (Ph)-positive chronic phase chronic myelogenous leukemia (CML-CP)
Authors: E. Jabbour, F. Giles, J. Cortes, S. O’Brien, F. Ravandi, G. Borthakur, G. Garcia-Manero, L. Letvak, A. Salvado, H. Kantarjian
Journal: Journal of Clinical Oncology (2006)

6591 Background: AMN107 is a novel, highly selective oral Bcr-Abl inhibitor which is 20–50-fold more potent than imatinib. High response rates with AMN107 were observed in all CML phases post imatinib failure. Methods: Study Aims: Evaluate the efficacy of AMN107in newly diagnosed Ph-positive CML-CP. Study Group and Therapy: Patients with newly diagnosed Ph-positive CML-CP were treated with AMN107 400 mg orally twice daily. Results: So far, 13 patients have been treated; median age 49 (range 24 to 72). Sokal risk at pretreatment: low - 10, intermediate - 2, high - 1. Five have reached the 3 month evaluation: all 5 (100%) had a complete cytogenetic response [CGCR] (Ph 0%). This is compared with a CGCR at 3 months of 36% with imatinib 400 mg/d and 55% with imatinib 800 mg/d in historical data of newly diagnosed patients treated at M. D. Anderson. The median QPCR with AMN at 3 months was 0.67% (range 0.3 to 3.0), compared with a median QPCR of 8% with imatinib 800 mg daily. Grade 3–4 myelosuppression was observed in 3/13 and other grade 3–4 side effects in 1/13 requiring temporary AMN107 interruption for &lt; 2 weeks and resumption at same dose level in the 3 patients with myelosuppression, and for 6 weeks+ in the patient with grade 3 elevation of liver enzymes which were reduced to grade 1 on last follow-up. One patient had a transient elevation of total bilirubin &gt; 3 mg/L which was self limited with continued therapy. Conclusions: Early results with AMN107 400 mg orally twice daily are encouraging in newly diagnosed CML. [Table: see text]
ACHIEVEMENT OF NEW EUROPEAN DYSLIPIDEMIA-GUIDELINE LOW-DENSITY LIPOPROTEIN CHOLESTEROL TREATMENT GOALS AFTER ACUTE CORONARY SYNDROME: INSIGHTS FROM ODYSSEY OUTCOMES
Authors: Ulf Landmesser, Jennifer McGinniss, Philippe Gabriel Steg, Deepak Bhatt, Vera Bittner, Rafael Diaz, Shaun Goodman, Robert A. Harrington, Johan Wouter Jukema, Aleksandras Laucevicius, Ivan Pecin, Robert Pordy, Steen Poulsen, Matthew Roe, Timothee Sourdille, Michael Szarek, Harvey White, Andreas Zeiher, Gregory G. Schwartz
Journal: Journal of the American College of Cardiology (2020)
Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis
Authors: Masataka Kuwana, Christiana Blair, Tomohiko Takahashi, Jonathan Langley, John G Coghlan
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To evaluate initial combination therapy with ambrisentan plus tadalafil (COMB) compared with monotherapy of either agent (MONO), and the utility of baseline characteristics and risk stratification in predicting outcomes, in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and the systemic sclerosis (SSc)–pulmonary arterial hypertension (PAH) subpopulation. Methods This post hoc analysis of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) study included patients with CTD-PAH from the modified intention-to-treat population. Time to clinical failure (TtCF) was assessed by baseline characteristics, treatment assignment and risk group (low, intermediate and high) at baseline and week 16. TtCF was compared between groups using Kaplan-Meier curves and Cox proportional hazards regression modelling. Results The analysis included 216 patients (COMB, n=117; MONO, n=99). The risk of clinical failure was lower with COMB versus MONO (risk reduction: CTD-PAH 51.7%, SSc-PAH 53.7%), particularly in patients with haemodynamic parameters characteristic of typical PAH without features of left heart disease and/or restrictive lung disease at baseline. The risk of clinical failure was lower with COMB versus MONO in the baseline low-risk group (HR not calculated due to no events in COMB), baseline intermediate-risk group (HR 0.519, 95% CI 0.297 to 0.905) and in the week 16 low-risk group (HR 0.069, 95% CI 0.009 to 0.548). Conclusions The benefit of COMB over MONO was demonstrated in patients with CTD-PAH, particularly in those with typical PAH haemodynamic characteristics at baseline. COMB is appropriate for patients categorised as low risk and intermediate risk at baseline and low risk at follow-up. Trial registration number NCT01178073 .
MANGANESE-ENHANCED T1MAPPING FOR THE DETECTION OF VIABLE AND STUNNED MYOCARDIUM FOLLOWING MYOCARDIAL INFARCTION
Authors: Nick Spath, Nick Spath, Giorgos Papanastasiou, Trisha Singh, Andrew Baker, Rob Janiczek, Gerry McCann, Marc Dweck, David E. Newby, Scott Semple
Journal: Journal of the American College of Cardiology (2020)
UTILIZATION OF GLUCOSE-LOWERING DRUGS IN PATIENTS WITH T2DM AND ESTABLISHED CVD IN US: A DESCRIPTIVE STUDY USING OPTUM CLINFORMATICS DATA
Authors: Michael Ganz, Anastasia Ustyugova, Nicola Sawalhi-Leckenby, Sabrina de Souza, Lu Zhang, Erik Gunnarsson, Ran Gao, Nihar R. Desai
Journal: Journal of the American College of Cardiology (2020)
Can resources save rationality? “Anti-Bayesian” updating in cognition and perception
Authors: Eric Mandelbaum, Isabel Won, Steven Gross, Chaz Firestone
Journal: Behavioral and Brain Sciences (2020)

Abstract Resource rationality may explain suboptimal patterns of reasoning; but what of “anti-Bayesian” effects where the mind updates in a direction opposite the one it should? We present two phenomena – belief polarization and the size-weight illusion – that are not obviously explained by performance- or resource-based constraints, nor by the authors’ brief discussion of reference repulsion. Can resource rationality accommodate them?
MSIsensor-Pro: Fast, Accurate, and Matched-Normal-Sample-Free Detection of Microsatellite Instability
Authors: Peng Jia, Xiaofei Yang, Li Guo, Bowen Liu, Jiadong Lin, Hao Liang, Jianyong Sun, Chengsheng Zhang, Kai Ye
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Microsatellite instability (MSI) is a key biomarker for cancer therapy and prognosis. Traditional experimental assays are laborious and time-consuming, and next-generation sequencing-based computational methods do not work on leukemia samples, paraffin-embedded samples, or patient-derived xenografts/organoids, due to the requirement of matched normal samples. Herein, we developed MSIsensor-pro, an open-source single sample MSI scoring method for research and clinical applications. MSIsensor-pro introduces a multinomial distribution model to quantify polymerase slippages for each tumor sample and a discriminative site selection method to enable MSI detection without matched normal samples. We demonstrate that MSIsensor-pro is an ultrafast, accurate, and robust MSI calling method. Using samples with various sequencing depths and tumor purities, MSIsensor-pro significantly outperformed the current leading methods in both accuracy and computational cost. MSIsensor-pro is available at https://github.com/xjtu-omics/msisensor-pro and free for non-commercial use, while a commercial license is provided upon request.
Relationship of bleeding to pathologic ulceration in a primary melanoma lesion.
Authors: Paul T Kang, Amy Louise Baker, James Warneke, Clara N Curiel, Joanne M. Jeter, Evan Hersh, Lee D. Cranmer
Journal: Journal of Clinical Oncology (2013)

9102 Background: Lesion bleeding (BL) is a catalyst symptom leading to melanoma (MEL) diagnosis and is associated with adverse outcomes. The pathophysiologic significance of BL has not been elucidated. We hypothesize that BL reflects pathologic ulceration (UL). Methods: This retrospective cohort study was conducted using data from 850 patients seen 2005-2009 at our center. Eligible patients reported the pre-diagnosis BL status of their primary lesion; determination of its UL status was also required. Demographic, clinical, pathologic and outcomes data were abstracted from records. Χ 2 and independent t-tests were used for univariate comparisons. Predictors of UL were analyzed with multiple logistic regression. Survival indices were analyzed by the Kaplan-Meier, log-rank, and Cox proportional hazards. Results: 190 patients with 193 MEL lesions were eligible. Median follow-up was 5.3 yr. 67 lesions bled prior to diagnosis; 68 demonstrated UL. BL and UL were associated with each other and with Breslow depth in univariate analyses; UL was also associated with age at diagnosis. Neither was associated with gender, lesion site, use of BL-associated drugs or Clark’s level. A logistic model was developed using BL, gender, lesion site, use of BL-associated drugs, and age at diagnosis. Only BL and age at diagnosis were associated with UL probability (OR=10.6/p&lt;0.001 and OR=1.04/p=0.006, respectively). BL was associated with worsened median relapse-free (RFS) and overall survival (OS) (median 1.16y vs. 1.96y, p=0.001 and 3.06 y vs. 3.41y, p=0.001), as was ulceration. When status of BL and UL were considered together, only UL predicted outcomes. A Cox model of clinical factors (BL, gender, age at diagnosis, lesion site) confirmed the association of BL with RFS and OS (HR 1.82/p=0.006 and HR 2.36/p=0.001). Addition of UL to the model abrogated BL’s predictive value. Conclusions: BL of primary MEL lesions is strongly associated with pathologic UL. When clinical parameters are considered, BL significantly predicts RFS and OS, although this value is lost once UL status is known. Our data are consistent with BL’s reflecting the ulceration status of a primary lesion. When UL status is unknown, BL may be able to serve as its surrogate marker.
RELATIONSHIP BETWEEN PERICORONARY ADIPOSE TISSUE INFLAMMATION, GLOBAL CORONARY FLOW RESERVE, AND EPICARDIAL FUNCTIONAL STENOSIS IN STABLE CORONARY ARTERY DISEASE PATIENTS WITH PRESERVED SYSTOLIC FUNCTION
Authors: Yoshihisa Kanaji, Tomoyo Sugiyama, Masahiro Hoshino, Masao Yamaguchi, Masahiro Hada, Toru Misawa, Yohei Sumino, Hidenori Hirano, Tomoki Horie, Kai Nogami, Hiroki Ueno, Taishi Yonetsu, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2020)
TOTAL ARTIFICIAL HEART: PERFORMANCE AS A BRIDGE TO HEALTH AND SURVIVAL
Authors: Gaurang Vaidya, Robert Cole, Carmelita Runyan, Francisco A. Arabia, Dominick Megna, Danny Ramzy, Dominick Emerson, Fardad Esmailian, Jon A. Kobashigawa, Jaime Moriguchi
Journal: Journal of the American College of Cardiology (2020)
Abstract 15929: Cost-Effectiveness Analysis of Empagliflozin as a Second-Line Therapy in Treatment Sequences of Patients With Type 2 Diabetes in The United States
Authors: Odette Reifsnider, Anuraag Kansal, Pratik Pimple, Valerie Aponte-Ribero, Sarah Brand, Sharash Shetty
Journal: Circulation (2019)

Objective: Cardiovascular disease (CVD) is a major comorbidity among type 2 diabetes (T2D) patients, contributing significantly to total medical costs. An estimated 20% of people with T2D have CVD,...
HIGH PREVALENCE OF HEART FAILURE WITH REDUCED EJECTION FRACTION AMONG PATIENTS WITH TRANSTHYRETIN CARDIAC AMYLOIDOSIS
Authors: Talal Asif, Tiago Araujo, Vasvi Singh, Tareq Alyousef, Javier Gomez Valencia, Rami Doukky, Saurabh Malhotra
Journal: Journal of the American College of Cardiology (2020)
EPIGENETIC READER INHIBITOR APABETALONE (RVX-208) COUNTERS PROINFLAMMATORY HYPERACTIVATION OF CD14+ MONOCYTES FROM PATIENTS WITH TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE
Authors: Sylwia Wasiak, Kim E. Dzobo, Mahnoush Bahjat, Brooke D. Rakai, Yannick Kaiser, Miranda Versloot, Jeffrey Kroon, Stephanie C. Stotz, Laura M. Tsujikawa, Li Fu, Dean Gilham, Christopher D. Sarsons, Michael Sweeney, Jan O. Johansson, Norman C.W. Wong, Erik S.G. Stroes, Ewelina Kulikowski
Journal: Journal of the American College of Cardiology (2020)
EFFECTS OF SINGLE-CYCLE REMOTE ISCHEMIC PRECONDITIONING AND/OR POSTCONDITIONING ON MYOCARDIAL INJURY IN PATIENTS UNDERGOING EMERGENCY OR ELECTIVE PERCUTANEOUS INTERVENTION
Authors: Kitcha Champasri, Nakarin Sansanayudh, Prasart Laotavorn, Chumpol Piamsomboon, Sopon Sanguanwong, Channarong Narksawasdee, Tanyarat Aramsareewong, Dilok Piyayotai, Pisit Hutayanon, Muenpetch Muenkaew, Kid Bhumimuang, Pawit Pipatwattanakul
Journal: Journal of the American College of Cardiology (2020)
Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β
Authors: Matthias Hepprich, Sophia J. Wiedemann, Benjamin L. Schelker, Beckey Trinh, Alessandra Stärkle, Marco Geigges, Jordan Löliger, Marianne Böni-Schnetzler, Gottfried Rudofsky, Marc Y. Donath
Journal: Cell Metabolism (2020)
Survival trends of patients with metastatic pancreatic cancer: A Surveillance Epidemiology and End Results registry trend analysis from 1988 to 2008.
Authors: Mathias Worni, Ulrich Guller, Rebekah Ruth White, Ricardo Pietrobon, Thomas Cerny, Beat Gloor, Dieter Koeberle
Journal: Journal of Clinical Oncology (2012)

e14544 Background: Pancreatic adenocarcinoma (PAC) is a disease with dismal prognosis. Only a minority of patients with PAC presents with a resectable tumor and can potentially be cured. Therapeutic options for non-resectable, metastatic tumors are limited and chemotherapy with or without radiation is purely palliative. The aim of the present study was twofold: first, to evaluate predictors of overall survival (OS), and second, to assess trends in OS and in the use of palliative radiotherapy among patients with metastatic PAC. Methods: Patients with metastatic PAC were extracted from the SEER cancer registry from 1988 to 2008. While SEER does contain information regarding radiotherapy and surgery, data on chemotherapy cannot be ascertained. Predictors and trends of OS were assessed using univariate and multivariable Cox proportional hazard models. The trend in use of radiotherapy was analyzed using univariate and multivariable logistic regression models. Results: Overall, 23,387 patients were included (mean age: 68.0±11.8 years); 47.0% of patients were female, tumor location was in the pancreatic head in 57.7% of all patients. Median OS was 3 months. In risk-adjusted analyses, tumor location in the pancreatic body/tail was associated with worse overall survival compared to tumors of the pancreatic head (HR: 1.10, CI: 1.07-1.13, p&lt;0.001). Increasing age, African-American ethnicity, male gender, and non-married civil status were associated with significantly worse OS. From 1988 to 2008, OS increased from a median survival of 2 (95% CI: 2-2) to 3 months (CI: 3-4) months (HR per year: 0.978, CI: 0.976-0.981, p&lt;0.001). From 1988 to 2008, radiotherapy use decreased from 13.2% to 5.8% (adj. OR per year: 0.95, CI: 0.93-0.96, p&lt;0.001). Conclusions: Metastatic PAC remains a disease with poor prognosis with only minimal improvement in OS over a 20-year time-period. The use of palliative radiotherapy has decreased. Tumor location in the body/tail of the pancreas, increasing age, African-American ethnicity, male gender, and non-married civil status were associated with worse OS. Future research is needed to improve OS of metastatic PAC on a population-based level.
IMPACT OF RENAL DYSFUNCTION ON OUTCOMES IN PATIENTS WITH SECONDARY MITRAL REGURGITATION: RESULTS FROM THE COAPT TRIAL
Authors: Gorav Ailawadi, Scott Lim, Saibal Kar, None Kar, Jacob M. Mishell, Brian Whisenant, Paul A. Grayburn, Michael Rinaldi, Ori Ben-Yehuda, Bahira Shahim, Bjorn Redfors, Nirat Beohar, Zixuan Zhang, JoAnn Lindenfeld, William Abraham, Michael Mack, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)