tbuckley/cabot-search huggingface dataset:
Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma
Authors: David M. Kurtz, Florian Scherer, Michael C. Jin, Joanne Soo, Alexander F.M. Craig, Mohammad Shahrokh Esfahani, Jacob J. Chabon, Henning Stehr, Chih Long Liu, Robert Tibshirani, Lauren S. Maeda, Neel K. Gupta, Michael S. Khodadoust, Ranjana H. Advani, Ronald Levy, Aaron M. Newman, Ulrich Dührsen, Andreas Hüttmann, Michel Meignan, René-Olivier Casasnovas, Jason R. Westin, Mark Roschewski, Wyndham H. Wilson, Gianluca Gaidano, Davide Rossi, Maximilian Diehn, Ash A. Alizadeh
Journal: Journal of Clinical Oncology (2018)

Outcomes for patients with diffuse large B-cell lymphoma remain heterogeneous, with existing methods failing to consistently predict treatment failure. We examined the additional prognostic value of circulating tumor DNA (ctDNA) before and during therapy for predicting patient outcomes.We studied the dynamics of ctDNA from 217 patients treated at six centers, using a training and validation framework. We densely characterized early ctDNA dynamics during therapy using cancer personalized profiling by deep sequencing to define response-associated thresholds within a discovery set. These thresholds were assessed in two independent validation sets. Finally, we assessed the prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index and interim positron emission tomography/computed tomography scans.Before therapy, ctDNA was detectable in 98% of patients; pretreatment levels were prognostic in both front-line and salvage settings. In the discovery set, ctDNA levels changed rapidly, with a 2-log decrease after one cycle (early molecular response [EMR]) and a 2.5-log decrease after two cycles (major molecular response [MMR]) stratifying outcomes. In the first validation set, patients receiving front-line therapy achieving EMR or MMR had superior outcomes at 24 months (EMR: EFS, 83% v 50%; P = .0015; MMR: EFS, 82% v 46%; P < .001). EMR also predicted superior 24-month outcomes in patients receiving salvage therapy in the first validation set (EFS, 100% v 13%; P = .011). The prognostic value of EMR and MMR was further confirmed in the second validation set. In multivariable analyses including International Prognostic Index and interim positron emission tomography/computed tomography scans across both cohorts, molecular response was independently prognostic of outcomes, including event-free and overall survival.Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.
Epstein–Barr Virus and Cancer
Authors: Paul J. Farrell
Journal: Annual Review of Pathology Mechanisms of Disease (2018)

Epstein-Barr virus (EBV) contributes to about 1.5% of all cases of human cancer worldwide, and viral genes are expressed in the malignant cells. EBV also very efficiently causes the proliferation of infected human B lymphocytes. The functions of the viral proteins and small RNAs that may contribute to EBV-associated cancers are becoming increasingly clear, and a broader understanding of the sequence variation of the virus genome has helped to interpret their roles. The improved understanding of the mechanisms of these cancers means that there are great opportunities for the early diagnosis of treatable stages of EBV-associated cancers and the use of immunotherapy to target EBV-infected cells or overcome immune evasion. There is also scope for preventing disease by immunization and for developing therapeutic agents that target the EBV gene products expressed in the cancers.
Functional <i>Ex Vivo</i> Assay Reveals Homologous Recombination Deficiency in Breast Cancer Beyond BRCA Gene Defects
Authors: Titia G. Meijer, Nicole S. Verkaik, Anieta M. Sieuwerts, Job van Riet, Kishan A.T. Naipal, Carolien H.M. van Deurzen, Michael A. den Bakker, Hein F.B.M. Sleddens, Hendrikus-Jan Dubbink, T. Dorine den Toom, Winand N.M. Dinjens, Esther Lips, Petra M. Nederlof, Marcel Smid, Harmen J.G. van de Werken, Roland Kanaar, John W.M. Martens, Agnes Jager, Dik C. van Gent
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Tumors of germline BRCA1/2 mutated carriers show homologous recombination (HR) deficiency (HRD), resulting in impaired DNA double-strand break (DSB) repair and high sensitivity to PARP inhibitors. Although this therapy is expected to be effective beyond germline BRCA1/2 mutated carriers, a robust validated test to detect HRD tumors is lacking. In this study, we therefore evaluated a functional HR assay exploiting the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh breast cancer tissue: the recombination REpair CAPacity (RECAP) test. Experimental Design: Fresh samples of 170 primary breast cancer were analyzed using the RECAP test. The molecular explanation for the HRD phenotype was investigated by exploring BRCA deficiencies, mutational signatures, tumor-infiltrating lymphocytes (TIL), and microsatellite instability (MSI). Results: RECAP was completed successfully in 125 of 170 samples (74%). Twenty-four tumors showed HRD (19%), whereas six tumors were HR intermediate (HRi; 5%). HRD was explained by BRCA deficiencies (mutations, promoter hypermethylation, deletions) in 16 cases, whereas seven HRD tumors were non-BRCA related. HRD tumors showed an increased incidence of high TIL counts (P = 0.023) compared with HR proficient (HRP) tumors and MSI was more frequently observed in the HRD group (2/20, 10%) than expected in breast cancer (1%; P = 0.017). Conclusions: RECAP is a robust functional HR assay detecting both BRCA1/2-deficient and BRCA1/2-proficient HRD tumors. Functional assessment of HR in a pseudo-diagnostic setting is achievable and produces robust and interpretable results.
Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans
Authors: Yoshito Yamashiro, Bui Quoc Thang, Seung Jae Shin, Caroline Antunes Lino, Tomoyuki Nakamura, Jungsil Kim, Kaori Sugiyama, Chiho Tokunaga, Hiroaki Sakamoto, Motoo Osaka, Elaine C. Davis, Jessica E. Wagenseil, Yuji Hiramatsu, Hiromi Yanagisawa
Journal: Circulation Research (2018)

Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated.
Abstract 18075: Mechanical Properties of Stents and Blood Vessels to Determine a Safe Strategy to Unzip Stents Within Growing Blood Vessels
Authors: Shyam K Sathanandam, T.K. Susheel Kumar, Deepthi Hoskoppal, Saradha Subramanian, Christopher Knott-Craig, Rush Waller
Journal: Circulation (2016)

Introduction: Unzipping of a stent is the technique by which a stent is fractured longitudinally using angioplasty balloons. This can allow for the stent to be further redilated and for implantation of a larger diameter stent within it. The technique may be useful in treating stenosis of infant blood vessels. The effectiveness and safety of unzipping stents depends in part on the mechanical properties of the stent and the blood vessel as well as the surrounding structures, the understanding of which is limited. Hypothesis: Unzipping of stents can be effective and safe if the appropriate stent is implanted in the appropriate blood vessel. Methods: 60 stents (7 stent types) were implanted in 12 neonatal piglets into different blood vessels. 3 months later, unzipping was attempted by dilating the stents till either the stent fractured or the vessel was injured. The ultimate tensile strength (UTS) of the different stent and vessel types was calculated. 6 piglets were sacrificed to determine histologic grade o...
Abstract 19756: Neutrophil to Lymphocyte Ratio Decreases After Ventricular Assist Device Implantation in Advanced Systolic Heart Failure but Remains Predictive of Mortality
Authors: Sakthi K Sundararajan, Michael S Kiernan, David DeNofrio, Amanda R Vest
Journal: Circulation (2016)

Background: Systolic heart failure (HF) is a low-grade systemic inflammatory state. Neutrophil to lymphocyte ratio (NLR) is a non-specific inflammatory marker in HF and known to be high pre-ventric...
Health Economic Analysis of Open and Robot-assisted Laparoscopic Surgery for Prostate Cancer Within the Prospective Multicentre LAPPRO Trial
Authors: Annabelle Forsmark, Jacob Gehrman, Eva Angenete, Anders Bjartell, Ingela Björholt, Stefan Carlsson, Jonas Hugosson, Tom Marlow, Karin Stinesen-Kollberg, Johan Stranne, Anna Wallerstedt, Peter Wiklund, Ulrica Wilderäng, Eva Haglind
Journal: European Urology (2018)

The rapid adoption of robot-assisted laparoscopy in radical prostatectomy has preceded data regarding associated costs. Qualitative evidence regarding cost outcomes is lacking. This study assessed how costs were affected by robot-assisted laparoscopic prostatectomy (RALP) compared with open surgery. Cost analysis was based on the dataset of the LAPPRO (Laparoscopic Prostatectomy Robot Open) clinical trial, which is a prospective controlled, nonrandomised trial of patients who underwent prostatectomy at 14 centres in Sweden between September 2008 and November 2011. Currently, data are available from a follow-up period of 24 mo. In the LAPPRO trial, RALP was compared with radical retropubic prostatectomy (RRP). Costs per surgical technique were assessed based on resource variable data from the LAPPRO database. The calculation of average costs was based on mean values; Swedish currency was converted to purchasing power parity US dollar (PPP$). All tests were two-tailed and conducted at α = 0.05 significance level. The cost analysis comprised 2638 men. Based on the LAPPRO trial data, RALP was associated with an increased cost/procedure of PPP$ 3837 (95% confidence interval: 2747–4928) compared with RRP. The result was sensitive to variations in caseload. Main drivers of overall cost were robotic system cost, operation time, length of stay, and sick leave. Limitations of the study include the uneven distribution between RALP and RRP regarding procedures in public/for-profit hospitals and surgeon/centre procedural volume. Based on the LAPPRO trial data, this study showed that RALP was associated with an increased cost compared with RRP in Swedish health care. There are many factors influencing the costs, making the absolute result dependent on the specific setting. However, by identifying the main cost drivers and/or most influential parameters, the study provides support for informed decisions and predictions. In this study, we looked at the cost outcome when performing prostatectomies by robot-assisted laparoscopic technique compared with open surgery in Sweden. We found that the robot-assisted procedure was associated with a higher mean cost.
Resolution of Atypical Lichen Myxedematosus Following Successful Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir-Velpatasvir Combination Therapy
Authors: Krystal M. Jones, Megan E. Shelton, Anthony C. Soldano, James Campbell
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Synergistic inhibition of aggressive breast cancer cell migration and invasion by cytoplasmic delivery of anti-RhoC silencing RNA and presentation of EPPT1 peptide on “smart” particles
Authors: Neha Kaushal, Gopinath Tiruchinapally, Yasemin Yuksel Durmaz, LiWei Bao, Rabia Gilani, Sofia D. Merajver, Mohamed E.H. ElSayed
Journal: Journal of Controlled Release (2018)
Biosensors: 3D‐Ridge Stocked Layers of Nitrogen‐Doped Mesoporous Carbon Nanosheets for Ultrasensitive Monitoring of Dopamine Released from PC12 Cells under K<sup>+</sup> Stimulation (Adv. Healthcare Mater. 16/2018)
Authors: Mohammed Y. Emran, Mohamed A. Shenashen, Hiromi Morita, Sherif A. El‐Safty
Journal: Advanced Healthcare Materials (2018)

Sherif El-Safty and co-workers report a biosensor design based on 3D-ridge N-doped mesoporous carbon nanosheets for selective sensing, and monitoring of monoamine neurotransmitters in a live neuron cell line. This protocol offers real, electro-signal tracking, sensitive quantification, selective discrimination, and fast-response signaling of dopamine for the diagnoses of schizophrenia, and Huntington's diseases.
Pain in Children With Severe Neurologic Impairment
Authors: Julie M. Hauer
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation‐positive patients
Authors: D. Bessis, F. Morice‐picard, E. Bourrat, C. Abadie, S. Aouinti, Cédric Baumann, M. Best, A.‐c. Bursztejn, Y. Capri, C. Chiaverini, C. Coubes, F. Giuliano, S. Hadj‐rabia, M.‐l. Jacquemont, D. Lacombe, S. Lyonnet, S. Mallet, J. Mazereeuw‐hautier, J. Miquel, Nicolas Molinari, B. Parfait, Charlotte Pernet, N. Philip, L. Pinson, N. Pouvreau, Y. Vial, P. Sarda, S. Sigaudy, A. Verloes, H. Cavé, D. Geneviève
Journal: British Journal of Dermatology (2018)

Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype–genotype correlations. We performed a 4‐year, large, prospective, multicentric, collaborative dermatological and genetic study. Forty‐five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype–genotype correlation was determined. A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.
Abstract 19292: Blood Telomere Length Predicts Clinical Outcome After Acute Myocardial Infarction: The Role of Oxidative Stress
Authors: Marios Margaritis, Fabio Sanna, George Lazaros, Ioannis Akoumianakis, Alexios A Antonopoulos, Laura Herdman, Rana Sayeed, Dimitris Tousoulis, Keith M Channon, Charalambos Antoniades
Journal: Circulation (2016)

Background: Experimental evidence suggests that telomere length (TL) is shortened by oxidative DNA damage, reflecting biological aging. We explore the value of blood TL (BTL) as a biomarker of oxidative stress in humans and test the clinical predictive value of BTL in acute myocardial infarction (AMI). Methods: Cohort 1 consists of 290 patients with AMI (prospective 1-year follow-up). Cohort 2 comprises 727 patients undergoing coronary artery bypass grafting (CABG). In both cohorts, blood samples on admission were used to measure BTL. In cohort 2, superoxide (O2.-) was measured in peripheral blood mononuclear cells (PBMNCs) and genotyping for genetic polymorphisms in the CYBA locus encoding for p22phox NADPH-oxidase subunit was performed. Results: In Cohort 1, BTL on admission was a strong predictor of cardiovascular mortality (4.121[1.39-12.22], P=0.011) during the 1st year post-AMI (Figure A, highest vs lowest tertile, P adjusted for age and other predictors: Age (per decade) 2.195[1.39-3.46], P=0.001, ...
Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial
Authors: Ajay Gupta, Judith Mackay, Andrew Whitehouse, Thomas Godec, Tim Collier, Stuart Pocock, Neil Poulter, Peter Sever
Journal: The Lancet (2018)
Cost-effectiveness of the 21-gene recurrence score assay in the setting of multifactorial decision making for chemotherapy in early-stage breast cancer.
Authors: Shelby D. Reed, Michaela A Dinan, Kevin A. Schulman, Gary H. Lyman
Journal: Journal of Clinical Oncology (2012)

1525 Background: The objective of this study was to incorporate evidence from two recently-published studies to reevaluate the cost-effectiveness of the 21-gene Recurrence Score (RS) assay (Oncotype DX) in the context of multifactorial decision making to guide the use of chemotherapy for node-negative, estrogen receptor–positive breast cancer in the United States from the societal and healthcare system perspectives. Methods: We developed a decision-analytic model to first cross-classify hypothetical patients by clinicopathologic characteristics according to the Adjuvant! using risk groups and RS risk groups. We generated estimates of long-term costs, survival, and quality-adjusted survival for the RS-guided and non–RS-guided strategies using a probabilistic state transition model. In addition to costs for the 21-gene assay, we assigned attributable costs for chemotherapy, hormonal therapy, monitoring for disease recurrence, and distant recurrence. For the societal perspective, we also considered incremental patient time costs. Costs and survival were discounted at 3% annually. Results: With the RS-guided strategy, 40.4% of patients were expected to receive chemotherapy relative to 47.3% in the non–RS-guided strategy. Targeted use of chemotherapy in the RS-guided strategy was expected to increase survival by 0.19 years (95% CI, 0.09 to 0.32) and 0.16 QALYs (95% CI, 0.08 to 0.28). Lifetime direct medical costs were expected to be $2692 (95% CI, 1546 to 3821) higher with the RS-guided strategy. The incremental cost-effectiveness ratios (ICERs) were $14,059 per life-year saved (95% CI, $6840-$28,912) and $16,677 per QALY (95% CI, $7613-$37,219). When incorporating lower indirect costs of $950 per patient, the ICERs were $9095 per life-year saved (95% CI, dominant-$23,397) and $10,788 per QALY (95% CI, $6840-$30,265). In probabilistic sensitivity analysis, more than 99% of the ICERs were less than $50,000 per life-year saved and per QALY. Conclusions: Our updated cost-effectiveness estimates are supportive of the economic value of the 21-gene RS assay in the setting of node-negative, estrogen receptor–positive breast cancer.
Abstract 12833: Can We Predict the Probability of ROSC by the Change in Cerebral rSO2 Value?
Authors: Ryosuke Takegawa, Tadahiko Shiozaki, Tomoya Hirose, Nobuto Mori, Tomohiko Sakai, Mitsuo Ohnishi, Takeshi Shimazu
Journal: Circulation (2016)

Introduction: There is no consensus on how long we should continue cardiopulmonary resuscitation (CPR). When determining this, it is important to assess the probability of return of spontaneous circulation (ROSC). We have been evaluating the usefulness of regional cerebral oxygen saturation (rSO2) during resuscitation since 2007. At the 2014 AHA congress, we reported that the probability of ROSC would be low if the rSO2 was less than 55%. In the present study, we focused on the relation between the rate of rSO2 increase and the occurrence of ROSC from the time of hospital arrival. Methods: This was a retrospective study of out-of-hospital cardiac arrest (OHCA) patients with successful measurement of rSO2 from December 2012 to December 2015. During CPR, rSO2 was recorded continuously from the forehead of the patients by a TOS-OR (TOSTEC, Japan). CPR for patients with OHCA was performed according to the 2010 JRC guidelines. Results: Ninety patients with OHCA (59 men, 31 women; mean age 74.8 years) were incl...
Abstract 18884: Proteomic Profiling Reveals Reduction in Electron Transport Chain Proteins in the Hearts of Hibernating Arctic Ground Squirrels Compared with Rats after Surgical Ischemia and Reperfusion: A Convergence of Mammalian Cardio-protective Strategies
Authors: Quintin J Quinones, Qing Ma, Zhiquan Zhang, Ricardo Henao, Erik Soderblom, Martin A Moseley, Christopher Newgard, Kelly Drew, Brian M Barnes, Mihai V Podgoreanu
Journal: Circulation (2014)

Introduction: Mammalian hibernation is a natural molecular adaptation to extreme environmental conditions with important applications for perioperative organ protection. We conducted an integrated proteomic analysis to identify species and season-specific correlates of the cardioprotective phenotype. Methods: Quantitative 2D-LC/LC-MS/MS was used in the myocardium of summer active arctic ground squirrels (AGS), winter hibernating AGS, and rats subjected to deep hypothermic cardiac arrest and reperfusion. Results: Hibernating AGS display robust cardioprotection in our model of I/R compared with rats using both biomarker (Fig 1) and echocardiographic assessment of cardiac injury. Proteomic analysis revealed significant reduction in subunits of all five electron transport chain (ETC) complexes in hibernating AGS compared with rats, only complex 5 showed increased expression of some subunits after I/R.Fig 2 Conclusions: Proteomic profiling revealed dichotomy in the cardioprotective adaptations employed by hibernating AGS and rat. The proteomic profile of hibernating AGS resembles that of myocardial hibernation in other mammals, with significant downregulation of mitochondrial ETC complexes. However, unlike myocardial hibernation in non-hibernators, AGS demonstrated downregulation of glycolytic and other myocardial energetic pathways with the exception of fatty acid oxidation. Sirtuin 3 - a key regulator of mitochondrial bioenergetics - was robustly upregulated in AGS, suggesting that preventing hyperacetylation of key metabolic enzymes may be a cardioprotective strategy employed by hibernators.