tbuckley/cabot-search huggingface dataset:
Lapatinib in HER2+ early breast cancer: Quality of life analysis.
Authors: Frances Boyle, Ian Edward Smith, Joyce O'Shaughnessy, Bent Ejlertsen, Manfred Kaufmann, Aman Buzdar, Pierre Fumoleau, William John Gradishar, Miguel Martin, Beverly Moy, Martine J. Piccart-Gebhart, Kathleen I. Pritchard, Deborah Lindquist, Mayur Amonkar, Yingjie Huang, Lisa Simone Williams, Qing Wang, Dianne M Finkelstein, Paul Edward Goss
Journal: Journal of Clinical Oncology (2012)

604 Background: TEACH, a randomized, double-blind, multi-center, phase III study evaluated the efficacy and safety of 12 months lapatinib (N=1571) versus placebo (N=1576) in women with HER2+ EBC. Patients receiving lapatinib more often reported treatment-related AEs (87% vs 47%) in the Intent-to-treat (ITT) population. The comparison of recurrence-free survival was not significant (p=.053). This analysis focuses on QOL in the ITT. Methods: Participants on TEACH completed the Short Form-36 version 2 (SF-36v2) at baseline and every 6 mo. for 24 mo. SF-36v2 captures physical, social, mental, emotional domains of patient perceptions; summary scores of physical and mental components are derived from domain scores using norm based scoring method. Changes in the domain and summary scores were compared between two groups using ANCOVAs. Missing post-baseline data were imputed using the last observation carried forward method. A clinically relevant change in scores was defined as a 3-5 point change. Results: For randomised patients who completed the SF-36, QOL scores decreased relative to baseline for all domains and summary scores across all assessments and treatment arms, however the decreases were small and not clinically meaningful. There were no statistically significant (p&lt; 0.05) or clinically meaningful differences between arms for the summary scores relative to baseline (Table). Conclusions: In HER2 positive EBC one year treatment with lapatinib is associated with a significant increase in AEs but it does not have a significant detrimental impact on QOL when compared to placebo. [Table: see text]
Association of adjuvant therapy in early-stage low-risk endometrial cancer with increased mortality: A statewide cancer registry analysis.
Authors: Michael R. Milam, Bin Huang, Mana Moghadamfalahi, Lynn Parker, Daniel Metzinger, Thomas Tucker
Journal: Journal of Clinical Oncology (2012)

5095 Background: National Comprehensive Cancer Network (NCCN) guidelines state that patients with early stage low risk endometrial cancer (defined with 2009 criteria as stage IA endometrioid endometrial cancer) may be managed with observation with consideration of adjuvant therapy.The premise of this study is to review the patterns of care of those patients who received adjuvant therapy and its impact on survival. Methods: This is a retrospective cohort analysis of 1044 women from 2004-2008 in the Kentucky Cancer Registry (KCR) one of the affiliates utilized in the Surveillance, Epidemiology and End Results (SEER) Program database. Inclusion criteria for the patients in this analysis were those women with 2009 Stage IA uterine cancer of endometrioid histology, moderate and well differentiated tumor grade, who received definitive primary surgery. Adjuvant therapy was defined as any postoperative radiotherapy and/or chemotherapy after definitive surgical treatment. Patients with adjuvant therapy after surgery (AT) were compared to those patients who underwent surgery only (SO). Chi-square tests were used to identify associations between type of treatment and clinical/demographic factors. K-M plots and Cox regression models were used to examine survival between the two treatment groups. Results: 5.3% (55/1044) of patients with early stage low risk endometrial cancer were treated with AT compared to 94.7% (989/1044) of SO patients.No statistical differences in mean age, race, tumor size, smoking status, insurance status, lymph node dissection and gynecologic oncology care were found among the AT or SO groups. Five year survival was significantly better in the SO cohort compared to the AT cohort (92% alive at 5 years for SO vs. 66% alive at 5 years; p&lt;0.0001). Controlling for other confounders in the multivariate Cox regression analysis, SO patients had substantially less risk for death compared to the AT groups (HR: 0.21; 95%CI 0.12-0.38; p&lt;0.0001). Conclusions: In this statewide cancer registry analysis, adjuvant therapy after surgery in early stage low risk endometrial cancer patients is uncommon and is associated with an increased risk of mortality.
Tuning the Antigen Density Requirement for CAR T-cell Activity
Authors: Robbie G. Majzner, Skyler P. Rietberg, Elena Sotillo, Rui Dong, Vipul T. Vachharajani, Louai Labanieh, June H. Myklebust, Meena Kadapakkam, Evan W. Weber, Aidan M. Tousley, Rebecca M. Richards, Sabine Heitzeneder, Sang M. Nguyen, Volker Wiebking, Johanna Theruvath, Rachel C. Lynn, Peng Xu, Alexander R. Dunn, Ronald D. Vale, Crystal L. Mackall
Journal: Cancer Discovery (2020)

Abstract Insufficient reactivity against cells with low antigen density has emerged as an important cause of chimeric antigen receptor (CAR) T-cell resistance. Little is known about factors that modulate the threshold for antigen recognition. We demonstrate that CD19 CAR activity is dependent upon antigen density and that the CAR construct in axicabtagene ciloleucel (CD19-CD28ζ) outperforms that in tisagenlecleucel (CD19-4-1BBζ) against antigen-low tumors. Enhancing signal strength by including additional immunoreceptor tyrosine-based activation motifs (ITAM) in the CAR enables recognition of low-antigen-density cells, whereas ITAM deletions blunt signal and increase the antigen density threshold. Furthermore, replacement of the CD8 hinge-transmembrane (H/T) region of a 4-1BBζ CAR with a CD28-H/T lowers the threshold for CAR reactivity despite identical signaling molecules. CARs incorporating a CD28-H/T demonstrate a more stable and efficient immunologic synapse. Precise design of CARs can tune the threshold for antigen recognition and endow 4-1BBζ-CARs with enhanced capacity to recognize antigen-low targets while retaining a superior capacity for persistence. Significance: Optimal CAR T-cell activity is dependent on antigen density, which is variable in many cancers, including lymphoma and solid tumors. CD28ζ-CARs outperform 4-1BBζ-CARs when antigen density is low. However, 4-1BBζ-CARs can be reengineered to enhance activity against low-antigen-density tumors while maintaining their unique capacity for persistence. This article is highlighted in the In This Issue feature, p. 627
A prospective clinical study evaluating current models for risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM).
Authors: Benjamin M. Cherry, Neha Korde, Mary Kwok, Elisabet E. Manasanch, Manisha Bhutani, Mary Ann Yancey, Marcia Mulquin, Irina Maric, Katherine R. Calvo, Raul Braylan, Maryalice Stetler-Stevenson, Constance Yuan, Prashant Tembhare, Adriana Zingone, Rene Costello, Mark J. Roschewski, Ola Landgren
Journal: Journal of Clinical Oncology (2012)

8088 Background: The updated (2010) International Myeloma Working Group criteria emphasize individual follow-up and development of early treatment trials for high risk SMM patients. To facilitate these goals, it is important to have reliable models for risk of progression to MM derived from prospective clinical studies. Current clinical risk models by the Mayo Clinic and the Spanish PETHEMA group stratify SMM patients as low (LR), intermediate (IR), or high risk (HR) of progression using bone marrow plasma cell fraction and protein levels (Mayo) and abnormal plasma cell fraction on flow cytometry with or without immunoparesis (Spanish). We report the first comparison of these models in a prospective natural history study. Methods: We evaluated 70 patients with SMM and determined the risk classifications of each using the Mayo and Spanish models. P values of comparisons between risk groups were calculated using Fisher’s exact test. Results: Among SMM patients classified as HR by the Spanish model (n=31), 2 patients (6%) were HR by the Mayo model; the remaining 17 (55%) and 12 (39%) patients were classified as IR and LR by the Mayo model, respectively. Among 2 SMM patients classified as HR by the Mayo model, both patients (100%) were HR by the Spanish model. There was significant disagreement between the models in identifying HR patients (HR v. non-HR, p&lt;0.0001). Similarly, of SMM patients classified as LR by the Spanish model (n=17), 11 patients (65%) were LR by the Mayo model; 6 (35%) were IR and 0 (0%) were HR by the Mayo model. Among SMM patients classified as LR by the Mayo model (n=36), 11 (31%) patients were classified as LR by the Spanish model; 13 (36%) were IR and 12 (33%) were HR by the Spanish model. There was significant disagreement between the models in identifying LR patients (LR v. non-LR, p=0.0016). Conclusions: The significant discordance between the Mayo Clinic and Spanish PETHEMA clinical risk models underscores the urgent need for biologically derived models that rely on molecular markers to predict disease progression. Such models are critical for counseling individual patients and for the development of early treatment studies that seek to prevent or delay progression to MM.
Abstract 69: Cardiac Fibrosis Induced by Mkk6-p38 Activation Alters Myocardial Stiffness and Myofilament Function
Authors: Farid Moussavi-Harami, Maria V Razumova, Jordan M Klaiman, Darrian Bugg, Michael Regnier, Jennifer Davis
Journal: Circulation Research (2017)

Heart failure with preserved ejection fraction (HFpEF) accounts for at least half of the patients with heart failure, but to date there are no proven therapies for these patients. Cardiac fibrosis and increased collagen content plays an important role in the pathophysiology of HFpEF. Studies in human HFpEF patients have indicated increased cardiac fibrosis, myocardial stiffness and myofilament calcium sensitivity. However, it is unclear how and if cardiac fibrosis directly alters myofilament function. In this study we used a new model of cardiac fibrosis genetically induced by the constitutive activation of MKK6-p38 (MKK6-Tg) signaling specifically in resident cardiac fibroblasts to determine the effect of fibrosis on myofilament stiffness and function. The MKK6-Tg mice develop interstitial and perivascular fibrosis in the heart accompanied with severe diastolic dysfunction, although systolic function remains normal. We measured the passive stiffness and isometric contractile properties of demembranated papillary muscle preparations. Our results show an increase in passive stiffness in demembranated papillary muscles from MKK6-Tg mice compared to NTG littermates when stretched to 24% from sarcomere length of 2.0 μM. Passive tension at SL=2.3 was significantly increased in MKK6-Tg mice (28±4 vs. 13±3 mN/mm 2 , P&lt;0.05) compared to NTG mice, which was ascribed to changes in Titin isoform as well as extracellular matrix composition. The MKK6-Tg mice also show an increase in Ca 2+ sensitivity (pCa 50 =5.72±0.05 vs. 5.56±0.02, P&lt;0.05). This was associated with an increased rate of force redevelopment in MKK6-Tg mice compared to NTG littermates (k TR =35±8 vs. 22±3 s -1 ). Towards understanding the mechanism of these myofilament changes we performed phosphate affinity electrophoresis and saw decreased phosphorylation of both Troponin I and Troponin T in MKK6-Tg hearts. There was no change in troponin I phosphorylation level at Ser23/24, indicating role of none-PKA mediated phosphorylation in mechanical changes seen in this model.
BPI20-021: Metastatic Renal Cell Carcinoma and Immunotherapy, Experience in a Third Level Hospital in Mexico City
Authors: Benigno Emmanuel Rodriguez Soto, Lorena López Zepeda, Daniela Vázquez Juarez, Alejandro Noguez Ramos, Alberto Villalobos Prieto, Samuel Rivera Rivera, Guillermo Manuel Olivares Beltrán, Raquel Gerson Cwilich
Journal: Journal of the National Comprehensive Cancer Network (2020)
Paclitaxel in combination with AT-101 induces apoptosis via supressing Bcl-2, bcl-XL, mcl-1 proteins in human breast cancer cells.
Authors: Burcu Cakar, Pinar Gursoy, Harika Atmaca, Asli Kisim, Emir Bozkurt, Selim Uzunoglu, Canfeza Sezgin, Ulus Ali Sanli, Bulent Karabulut, Ruchan Uslu, Burcak Karaca
Journal: Journal of Clinical Oncology (2013)

e13578 Background: Paclitaxel, a microtubule stabilizing agent, has been a standard of care for breast cancer. AT-101, is an -/- enantiomer of gossypol, inhibits the Bcl-2 family proteins which contain BH3 domain. We reported previously that Paclitaxel in combination with AT-101 showed strong synergistic cytotoxic and apoptotic effects in human breast cancer cells. In this study, to elucidate the molecular mechanisms involved in the apoptotic effect of AT-101/Paclitaxel combination treatment in breast cancer cells, we investigated the possible roles of anti-apoptotic Bcl-2, Bcl-XL and Mcl-1 proteins which contain BH3 domain. Involvement of caspase 3 and 7 activation was also investigated. Methods: Human breast cancer cells were treated with increasing concentrations of drugs alone or with the synergistic combination doses of AT-101 and Paclitaxel. Cell Death Detection Elisa Plus Kit (Roche) was used to detect apoptosis. Caspase 3/7 activity was evaluated by Caspase-Glo 3/7 (Promega, Madison, WI) kit. Changes in the mRNA levels of Bcl-2, Bcl-XL and Mcl-1 genes were evaluated by qRT-PCR. Expression levels of these proteins were also investigated by Western blot analysis. Results: Combined treatment was shown to have strong synergistic apoptotic effects in MCF-7 and MDA- MB-231 human breast cancer cells. mRNA levels of Bcl-2, Bcl-XL and Mcl-1 molecules were reduced by the combination treatment in both cell lines. In parallel with mRNA levels, Bcl-2, Bcl-XL and Mcl-1 protein levels were significantly reduced after this novel drug combination. Combined treatment also induced caspase 3/7 activation in breast cancer cells. Conclusions: These preliminary data suggest that anti-apoptotic proteins such as Bcl-2, Bcl-XL and Mcl-1 may play important role in the underlying mechanistic rationale of apoptotic effect of AT-101/paclitaxel combination, while pro-apoptotic Bcl-2 related genes (Caspase-3 and Caspase-7) also seem to regulate this synergistic interaction.
Validation of the use of a fluorescent PARP1 inhibitor for the detection of oral, oropharyngeal and oesophageal epithelial cancers
Authors: Susanne Kossatz, Giacomo Pirovano, Paula Demétrio De Souza França, Arianna L. Strome, Sumsum P. Sunny, Daniella Karassawa Zanoni, Audrey Mauguen, Brandon Carney, Christian Brand, Veer Shah, Ravindra D. Ramanajinappa, Naveen Hedne, Praveen Birur, Smita Sihag, Ronald A. Ghossein, Mithat Gönen, Marshall Strome, Amritha Suresh, Daniela Molena, Ian Ganly, Moni A. Kuriakose, Snehal G. Patel, Thomas Reiner
Journal: Nature Biomedical Engineering (2020)
Abstract 15775: Prevalence, Dynamic Changes, and Prognostic Implications of Secondary Tricuspid Regurgitation in Patients With Arrhythmogenic Right Ventricular Cariomyopathy
Authors: Hyeonju Jeong, Shinjeong Song, Jah Yeon Choi, Kang-Un Choi, Geu-Ru Hong, Jong-Won Ha, Chi Young Shim
Journal: Circulation (2018)

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare primary cardiomyopathy involving right ventricle (RV). Because ARVC is characterized by RV dilatation and dysfunction, s...
Highly brain-permeable apoferritin nanocage with high dysprosium loading capacity as a new T2 contrast agent for ultra-high field magnetic resonance imaging
Authors: Hee-Kyung Kim, Ah Rum Baek, Garam Choi, Jung-jin Lee, Ji-ung Yang, Hoesu Jung, Taekwan Lee, Dongkyu Kim, Minsup Kim, ArtE. Cho, Gang Ho Lee, Yongmin Chang
Journal: Biomaterials (2020)
Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study
Authors: Virginie Royal, Nelson Leung, Stéphan Troyanov, Samih H. Nasr, Laure Écotière, Richard LeBlanc, Benjamin A. Adam, Andrea Angioi, Mariam P. Alexander, Anna Maria Asunis, Antonella Barreca, Paola Bianco, Camille Cohen, Maria E. Drosou, Huma Fatima, Roberta Fenoglio, François Gougeon, Jean-Michel Goujon, Guillermo A. Herrera, Bertrand Knebelmann, Nicola Lepori, Francesca Maletta, Rita Manso, Shveta S. Motwani, Antonello Pani, Marion Rabant, Helmut G. Rennke, Dario Rocatello, Frida Rosenblum, Paul W. Sanders, Afonso Santos, Karina Soto, Banu Sis, Guy Touchard, Christopher P. Venner, Frank Bridoux
Journal: Blood (2020)
Nationally and regionally representative analysis of 1.65 million children aged under 5 years using a child-based human development index: A multi-country cross-sectional study
Authors: Jan-Walter De Neve, Kenneth Harttgen, Stéphane Verguet
Journal: PLoS Medicine (2020)

Background Education and health are both constituents of human capital that enable people to earn higher wages and enhance people's capabilities. Human capabilities may lead to fulfilling lives by enabling people to achieve a valuable combination of human functionings—i.e., what people are able to do or be as a result of their capabilities. A better understanding of how these different human capabilities are produced together could point to opportunities to help jointly reduce the wide disparities in health and education across populations. Methods and findings We use nationally and regionally representative individual-level data from Demographic and Health Surveys (DHS) for 55 low- and middle-income countries (LMICs) to examine patterns in human capabilities at the national and regional levels, between 2000 and 2017 (N = 1,657,194 children under age 5). We graphically analyze human capabilities, separately for each country, and propose a novel child-based Human Development Index (HDI) based on under-five survival, maternal educational attainment, and measures of a child's household wealth. We normalize the range of each component using data on the minimum and maximum values across countries (for national comparisons) or first-level administrative units within countries (for subnational comparisons). The scores that can be generated by the child-based HDI range from 0 to 1. We find considerable heterogeneity in child health across countries as well as within countries. At the national level, the child-based HDI ranged from 0.140 in Niger (with mean across first-level administrative units = 0.277 and standard deviation [SD] 0.114) to 0.755 in Albania (with mean across first-level administrative units = 0.603 and SD 0.089). There are improvements over time overall between the 2000s and 2010s, although this is not the case for all countries included in our study. In Cambodia, Malawi, and Nigeria, for instance, under-five survival improved over time at most levels of maternal education and wealth. In contrast, in the Philippines, we found relatively few changes in under-five survival across the development spectrum and over time. In these countries, the persistent location of geographical areas of poor child health across both the development spectrum and time may indicate within-country poverty traps. Limitations of our study include its descriptive nature, lack of information beyond first- and second-level administrative units, and limited generalizability beyond the countries analyzed. Conclusions This study maps patterns and trends in human capabilities and is among the first, to our knowledge, to introduce a child-based HDI at the national and subnational level. Areas of chronic deprivation may indicate within-country poverty traps and require alternative policy approaches to improving child health in low-resource settings.
THE IMPACT OF FRAILTY ON EARLY CHANGES IN PHYSICAL ACTIVITY AFTER TRANSCATHETER TRICUSPID VALVE REPAIR: AN ANALYSIS OF WEARABLE ACTIVITY MONITORING IN THE CLASP TR EARLY FEASIBILITY STUDY
Authors: Philip Green, Christine Chung, Shannon Murphy, Ahmad Al-Ghusain, Sarah Mollenkopf, Ted Feldman, Charles Davidson, Mackram Eleid, Robert Kipperman, Robert Smith, Scott Lim, Firas Zahr, William A. Gray, Adam Greenbaum, Martin Leon, Susheel K. Kodali
Journal: Journal of the American College of Cardiology (2020)
The Ethics of Disclosing Diagnostic Errors
Authors: Grant J. Shafer, Frank X. Placencia
Journal: JAMA Pediatrics (2020)

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
COMPARISON OF MACHINE LEARNING (ML) METHODS WITH CONVENTIONAL STATISTICAL MODELS (CSM) FOR PREDICTION OF MORTALITY IN MYOCARDIAL INFARCTION (MI) PATIENTS
Authors: Douglas Lee, Sung Min Cho, Peter Austin, Husam Abdel-Qadir, Cameron Taheri, Cassandra Freitas, George Tomlinson, Davide Chicco, Bo Wang, Slava Epelman, Patrick R. Lawler, Filio Billia, Anthony Gramolini, Heather Joan Ross
Journal: Journal of the American College of Cardiology (2020)
PCL20-116: Can Antisense Oligonucleotides Targeted to K-Ras Gene Inhibit the Tumor Growth, Invasiveness and Expression of MMP-2 and MMP-9 In Vitro and In Vivo in Hamster Experimental Pancreatic Cancer Model?
Authors: Cintia Yoko Morioka, Marcel Cerqueira Cesar Machado, Jose Pinhata Otoch, Luma Princess Schneider, Edgard Mesquita Rodrigues Lima, Marcelo Engracia Garcia, Seiji Saito, Akiharu Watanabe, Eduardo Kenichi Morioka, Ching Cheng Huang
Journal: Journal of the National Comprehensive Cancer Network (2020)

"PCL20-116: Can Antisense Oligonucleotides Targeted to K-Ras Gene Inhibit the Tumor Growth, Invasiveness and Expression of MMP-2 and MMP-9 In Vitro and In Vivo in Hamster Experimental Pancreatic Cancer Model?" published on 20 Mar 2020 by National Comprehensive Cancer Network.
EPICARDIAL FAT THICKNESS AND HEPATIC FAT IN A REMOTE NATIVE POPULATION WITH VERY LOW RATES OF CORONARY CALCIUM
Authors: Randall C. Thompson, Benjamin Trumble, Angela Neunuebel, Ashna Mahadev, L. Samuel Wann, Christopher Rowan, Adel Hassan Allam, Bruno Frohlich, Edmond Seabright, Daniel K. Cummings, Jonathan Stiegiltz, Jagat Narula, Samantha King, Kevin Kennedy, Michael Gurven, Gregory Thomas, Hillard Kaplan
Journal: Journal of the American College of Cardiology (2020)
INTRAVASCULAR ULTRASOUND USE FOR STENT OPTIMIZATION AND 1-YEAR OUTCOMES IN PATIENTS UNDERGOING CTO-PCI: INSIGHTS FROM THE PROGRESS-CTO REGISTRY
Authors: Evangelia Vemmou, Jaikirshan Khatri, Anthony Doing, Philip Dattilo, Catalin Toma, Farouc Jaffer, Dimitrios Karmpaliotis, Abdul Sheikh, Habib Samady, Khaldoon Alaswad, Raj Chandwaney, Santiago Garcia, Michael Megaly, Mohamed Omer, Larissa Stanberry, Iosif Xenogiannis, Ilias Nikolakopoulos, Fotios Gkargkoulas, Wissam A. Jaber, Taral Patel, Brian Jefferson, Bavana Rangan, M. Nicholas Burke, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2020)