tbuckley/cabot-search huggingface dataset:
Use of Circulating Tumor DNA for Cancer Immunotherapy
Authors: Alexandra Snyder, Michael P. Morrissey, Matthew D. Hellmann
Journal: Clinical Cancer Research (2019)

Liquid biopsy offers a versatile, noninvasive opportunity to diagnose, characterize, and monitor disease in patients with cancer. There are particularly promising applications with which to use liquid biopsies to predict and evaluate response to immunotherapy. Circulating tumor DNA (ctDNA) can reflect the genomic state of a patient's overall disease and, thus, might identify prognostic and predictive biomarkers for immune checkpoint inhibitor therapy. ctDNA might also be a proxy for a patient's overall disease burden, which could be used for early diagnosis and monitoring treatment response. These applications can enable novel trial designs, such as enrollment of early-stage patients with a high risk for relapse, and the evaluation of response patterns unique to immunotherapies. However, barriers to the widespread adoption of ctDNA assessment remain, including the absence of standardized procedures for collecting and processing ctDNA samples and relatively limited data on clinical utility. Identifying and solving these challenges could allow ctDNA to become a powerful clinical and research tool in the era of personalized immunotherapy.
Involvement of K-RAS mutations and amino acid substitutions in the survival of metastatic colorectal cancer patients.
Authors: Elisabeth Pérez-Ruiz, Julia Alcaide, Teresa Pereda, Dolores Bautista, Francisco Rivas Ruiz, R. Villatoro, Maximino Redondo, Diego Perez, Antonio Rueda
Journal: Journal of Clinical Oncology (2012)

e14116 Background: The efficacy against of epidermal growth factor therapy was found to be limited to those wild-type K-RAS tumours, suggesting a predictive value of response. However, the prognostic value of K-RAS status is controversial. The aim is to determine the relationship between K-RAS mutations and types of amino acid changes with the survival (OS) of metastatic colorectal patients (mCRC). Methods: The retrospective analysis included 120 patients diagnosed of mCRC. The presence and type of K-RAS mutations were analysed. Similarly, the clinical and pathological variables were also collected including OS. Results: The sample characteristics were summarized in Table 1. 53.3% of tumours were wild-type and 46.7 mutated KRAS. In mutated patients, codon 12 was affected in 76.79% and codon 13 in 23.21%. The median OS for wild-type was 31.6 months. In mutated patients (codon 12 or 13), median OS was 24.8 and 17.8 months (p=0.37), respectively. In the univariate analysis, mutated K-RAS was associated with stage IV at diagnosis (p&lt;0.005). The relationship between OS and amino acid mutation are summarized in table 1. Conclusions: Our study suggest that the types of mutation or amino acid changes of KRAS in mCRC provides prognostic information. These data need to be confirmed in prospective or controlled trials. [Table: see text]
SUNRISE-DI study: decision impact of the 12-gene recurrence score (12-RS) assay on adjuvant chemotherapy recommendation for stage II and IIIA/B colon cancer
Authors: J. Watanabe, T. Sato, Y. Kagawa, E. Oki, Y. Kuboki, M. Ikeda, H. Ueno, T. Kato, T. Kusumoto, T. Masuishi, K. Yamaguchi, A. Kanazawa, T. Nishina, H. Uetake, T. Yamanaka, T. Yoshino
Journal: Annals of Oncology (2019)
Targeting Kinome Reprogramming for Overcoming Ibrutinib-Resistance (IR) in Mantle Cell Lymphoma (MCL)
Authors: Xiaohong Zhao, Huijuan Jiang, Michelle Wang, Tao Li, Jing Gao, Tint Lwin, Yuan Ren, Eduardo Sotomayor, Bijal D. Shah, Jianguo Tao
Journal: Blood (2018)
Designing noninferiority tuberculosis treatment trials: Identifying practical advantages for drug regimens with acceptable effectiveness
Authors: Piero L. Olliaro, Michel Vaillant
Journal: PLoS Medicine (2019)

In this Collection Review for the Novel Treatments for Tuberculosis Collection, Piero Olliaro and Michael Vaillant discuss the considerations when choosing a non-inferiority margin that is meaningful from statistical, ethical, clinical, and health standpoint.
Abstract 13335: Impaired B-type Natriuretic Peptide Effets on Neutrophil Burst in Heart Failure Patients
Authors: Saifei Liu, Doan T Ngo, Yuliy Y Chirkov, Simon Stewart, John D Horowitz
Journal: Circulation (2013)

Purpose: The cardiac natriuretic peptide system is activated in heart failure (HF); however, B-type natriuretic peptide (BNP)-based restoration of homeostasis is inadequate. The equivocal clinical ...
Reply to Bernhard Liedl, Klaus Goeschen, and Florian Wagenlehner’s Letter to the Editor re: Benoit Peyronnet, Emma Mironska, Christopher Chapple, et al. A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment. Eur Urol 2019, 75:988–1000
Authors: Benoit Peyronnet, Christopher Chapple, Jean-Nicolas Cornu
Journal: European Urology (2019)
Comparison of clinical scoring systems in aggressive B-cell lymphomas (BCL): An individual patient-level analysis across international trials (SEAL).
Authors: Amy S. Ruppert, Jesse G. Dixon, Gilles A. Salles, Anna K. M. Wall, David Cunningham, Viola Poeschel, Corinne Haioun, Herve Tilly, Herve Ghesquieres, Marita Ziepert, Jocelyne Flament, Christopher Flowers, Qian Shi, Norbert Shmitz
Journal: Journal of Clinical Oncology (2019)

7544 Background: Great heterogeneity in survival exists for patients (pts) newly diagnosed with aggressive BCL. Three scoring systems based on simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the international prognostic index (IPI), revised-IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We studied BCL pts treated with R-CHOP to determine which scoring systems best identifies subgroups with poor outcomes that might benefit from new approaches. Methods: Individual pt data from 7 multicenter trials (1998-2009) of pts with BCL (86% DLBCL) treated front-line with R-CHOP (or variant) were analyzed to determine whether IPI, R-IPI, or NCCN-IPI best discriminated overall survival (OS). The concordance index (c-index) from a proportional hazards model, stratifying on trial and induction therapy, quantified predictive accuracy of each scoring system. Results: 2561 pts (median age 63 yrs, 56% male) were classified into IPI, R-IPI, and NCCN-IPI risk groups (Table). With a median follow-up of 5 yrs, NCCN-IPI had the greatest absolute difference in OS estimates between the highest and lowest risk groups at 1, 3, and 5 yrs, and best discriminated OS (c-index = 0.631, Table). Conclusions: In an independent and large cohort of pts, NCCN-IPI performs best in risk-stratifying pts with aggressive BCL, readily distinguishing pts at high and low risk for treatment failure using clinical parameters (5-yr OS between 48 and 92%). Improvement over the simpler IPI appears incremental, and IPI may remain a valuable alternative. Work integrating molecular features of the tumor into the (NCCN-) IPI is in progress to define high risk groups where targeted novel approaches are needed most. [Table: see text]
Why a developmental cognitive neuroscience approach may be key for future-proofing microbiota-gut-brain research
Authors: Nicola Johnstone, Kathrin Cohen Kadosh
Journal: Behavioral and Brain Sciences (2019)

Abstract Here we argue that a multidisciplinary research approach, such as currently practised in the field of developmental cognitive neuroscience, is key to maintaining current momentum and to future-proof the field of microbiome-gut-brain research. Moreover, such a comprehensive approach will also bring us closer to our aims of translation and targeted intervention approaches to improve mental health and well-being.
Development of a Data Portal for Aggregation and Analysis of Genomics Data in Familial Platelet Disorder with Predisposition to Myeloid Malignancy - the RUNX1.DB
Authors: Anna L. Brown, Mark Armstrong, David Lawrence, Paul Wang, Peer Arts, Nicolas Duployez, Jane Churpek, Kiran Tawana, Erin Degelman, Georges Natsoulis, Monica L. Guzman, Mrinal M. Patnaik, Akiko Shimamura, Alan B. Cantor, Tim Ripperger, Brigitte Schlegelberger, Doris Steinemann, Courtney D. DiNardo, Cristina Mecucci, Elvira DRP Velloso, Fabio PS Santos, Marcela CA Silva, Uma Borate, Shannon K. McWeeney, Grzegorz Nalepa, Susanne Ragg, Erika Mijin Kwon, Anupriya Agarwal, Stephen Langabeer, Jeffery M. Klco, Jun J. Yang, Cecily Forsyth, Sally Mapp, Helen Mar Fan, Lesley Rawlings, Rachel Susman, Sue Morgan, Andrew H Wei, Inderjeet Dokal, Tom Vulliamy, Devendra K Hiwase, Deepak Singhal, Susan Branford, Elli Papaemmanuil, Jean Soulier, Stefan Fröhling, Alwin Kramer, Guy Sauvageau, Neil Morgan, Carolyn Owen, Csaba Bödör, Jude Fitzgibbon, Hugh Y. Rienhoff, Mineo Kurokawa, Lucy Godley, Claude Preudhomme, Paul P Liu, Nicola Poplawski, Christopher N. Hahn, Hamish S. Scott
Journal: Blood (2018)
Measurement equivalence of the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare survey items between non-Hispanic whites and Asians.
Authors: Ron D. Hays, Neetu Chawla, Erin E. Kent, Neeraj K. Arora
Journal: Journal of Clinical Oncology (2016)

259 Background: Asians report worse experiences with care than Whites. This could be due to true differences in care received, expectations about care, or survey response styles. To examine measurement equivalence of the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare survey items between Whites and Asians. Methods: We conducted multiple group confirmatory factor analyses to evaluate measurement equivalence of CAHPS Medicare survey data between White and Asian Medicare beneficiaries for three CAHPS reporting composites (communication with personal doctor, access to care, plan customer service) and global ratings of care using pooled CAHPS data from 2007-2011. Responses were obtained from non-Hispanic whites (n = 1,326,410) and Asians (n = 40,672). The median age for whites was 70, with 24% 80 or older, and 70 for Asians, with 23% 80 or older. Fifty-eight percent of the whites and 56% of the Asians were female. Results: A model without group-specific estimates fit the data as well as a model that included 12 group-specific estimates suggested by Lagrange multiplier tests (Comparative Fit Index = 0.922, Root Mean Square Error of Approximation = 0.064). Three of the 12 group-specific estimates consisted of 7 factor loadings, 3 measured variable errors, and 2 item intercepts. Six of the factor loadings were larger for Asians than for whites. Conclusions: This study provides general support for measurement equivalence in response to the CAHPS Medicare survey composites (communication, access, customer service) and global ratings between White and Asian respondents, supporting comparison of care experiences for the two groups.
Abstract 11534: Activation of ATP-sensitive K+ Channels Favors Initiation and Acceleration of Ischemia-related Atrial Fibrillation
Authors: Masatoshi Yamazaki, Haruo Honjo, Uma Mahesh R Avula, Krishna Bandaru, Venkata Subbarao C Boppana, Auras Atreya, Itsuo Kodama, Kaichiro Kamiya, Jérôme Kalifa
Journal: Circulation (2012)

Introduction: Atrial ischemia has been recognized as a pathogenic factor predisposing to atrial fibrillation (AF). However, underlying mechanisms of AF initiation and maintenance remain to be clari...
Imaging Characteristics of Coexisting Primary Pulmonary Carcinoid Tumor and Multiple Myeloma on 18F-FDG and 68Ga-DOTATATE PET/CT
Authors: Yang Lu
Journal: Clinical Nuclear Medicine (2019)

Abstract A 69-year-old man with recurrent multiple myeloma underwent FDG PET/CT evaluation. A pulmonary nodule without higher-than-background FDG avidity was later biopsied as a low-grade neuroendocrine tumor. On further 68 Ga-DOTATATE PET/CT evaluation of patient’s neuroendocrine tumor, the lytic myeloma lesions revealed only mild DOTATATE avidity while the primary pulmonary neuroendocrine tumor showed intense DOTATATE uptake. The distinct imaging characteristics of different primary malignancies correlated with their underlying different pathology.
BAP1 Loss Is Associated with DNA Methylomic Repatterning in Highly Aggressive Class 2 Uveal Melanomas
Authors: Matthew G. Field, Jeffim N. Kuznetsov, Parker L. Bussies, Louie Z. Cai, Karam A. Alawa, Christina L. Decatur, Stefan Kurtenbach, J. William Harbour
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The strong association between BAP1 mutations and metastasizing Class 2 uveal melanoma (UM) suggests that epigenetic alterations may play a significant role in tumor progression. Thus, we characterized the impact of BAP1 loss on the DNA methylome in UM. Experimental Design: Global DNA methylation was analyzed in 47 Class 1 and 45 Class 2 primary UMs and in UM cells engineered to inducibly deplete BAP1. RNA-Seq was analyzed in 80 UM samples and engineered UM cells. Results: Hypermethylation on chromosome 3 correlated with downregulated gene expression at several loci, including 3p21, where BAP1 is located. Gene set analysis of hypermethylated and downregulated genes identified axon guidance and melanogenesis as deregulated pathways, with several of these genes located on chromosome 3. A novel hypermethylated site within the BAP1 locus was found in all Class 2 tumors, suggesting that BAP1 itself is epigenetically regulated. Highly differentially methylated probes were orthogonally validated using bisulfite sequencing, and they successfully distinguished Class 1 and Class 2 tumors in 100% of cases. In functional validation experiments, BAP1 knockdown in UM cells induced methylomic repatterning similar to UM tumors, enriched for genes involved in axon guidance, melanogenesis, and development. Conclusions: This study, coupled with previous work, suggests that the initial event in the divergence of Class 2 UM from Class 1 UM is loss of one copy of chromosome 3, followed by mutation of BAP1 on the remaining copy of chromosome 3, leading to the methylomic repatterning profile characteristic of Class 2 UMs.
Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement
Authors: Ian J Neeland, Robert Ross, Jean-Pierre Després, Yuji Matsuzawa, Shizuya Yamashita, Iris Shai, Jaap Seidell, Paolo Magni, Raul D Santos, Benoit Arsenault, Ada Cuevas, Frank B Hu, Bruce Griffin, Alberto Zambon, Philip Barter, Jean-Charles Fruchart, Robert H Eckel
Journal: The Lancet Diabetes & Endocrinology (2019)
Pooled safety summary for patients treated with the CD22-directed cytotoxin moxetumomab pasudotox-tdfk.
Authors: Robert J. Kreitman, Steven Coutre, Cynthia Elesinmogun, Nataliya Kuptsova-Clarkson, Xia Li, Ira Pastan, Douglas Edward Gladstone
Journal: Journal of Clinical Oncology (2019)

7014 Background: Moxetumomab pasudotox-tdfk was FDA-approved in 2018 for the treatment of adults with relapsed/refractory hairy cell leukemia (HCL) who have received ≥2 prior therapies, including a purine nucleoside analog. Methods: The pooled integrated safety summary included all adult patients (N=165) treated with ≥1 dose of moxetumomab across 5 open-label, single-arm clinical trials. Two trials included patients with HCL (N=129, with N=80 in the pivotal phase 3 trial) and 3 trials included patients with non-Hodgkin lymphoma (N=15) or chronic lymphocytic leukemia/small lymphocytic lymphoma (N=21). Overall, 81% were male, median age was 60 years (range 34–84) and 94% had an ECOG ≤1. Results: The most common adverse events (AEs) with moxetumomab were peripheral edema (41%), hypoalbuminemia (35%), and nausea (35%). Serious AEs occurred in 47 (28.5%) patients and were considered treatment-related in 21 (12.7%) patients. Treatment-related AEs were mainly grade 1/2; the most common were peripheral edema (32%), hypoalbuminemia (32%), increased ALT (29%), increased AST (28%), nausea (26%), headache (24%), pyrexia (23%), fatigue (22%), and myalgia (20%). In total, 19 deaths (11.5% of patients) occurred (including 3 in the pivotal trial), with most (13) due to underlying disease and 6 due to AEs (none were assessed as treatment-related by the investigators, however, 1 fatal AE in a non-HCL patient was re-assessed by the Sponsor as possibly related to moxetumomab). In 16 patients (9.7%), a treatment-related AE led to treatment discontinuation, with hemolytic uremic syndrome HUS; 3.6%) and capillary leak syndrome (CLS; 2.4%) the most common. Treatment-related AEs resulted in dose delay, omission or treatment interruption in 11 patients (6.7%). Conclusions: Moxetumomab had an acceptable safety profile based on pooled data from 165 adult patients with hematologic malignancies, with few treatment-related discontinuations. Proactive monitoring of patients is important to manage AEs. These results are consistent with results from the pivotal phase 3 trial in patients with HCL. Clinical trial information: NCT01829711, NCT00586924, NCT00587457, NCT00587015, NCT01030536.
Down Syndrome AML Is Unique in Phenotype Both at Diagnosis and in Post Chemotherapy Regeneration
Authors: Elisabeth R Wilson, Lisa Eidenschink Brodersen, Barbara Katharina Zehentner, Andrew J. Menssen, Andrew P. Voigt, Laura Pardo, Denise A. Wells, Johann Hitzler, Jason N. Berman, Todd A. Alonzo, Samir B. Kahwash, Soheil Meshinchi, Michael R. Loken
Journal: Blood (2016)
Implications of Gestational Weight Gain in Studies of Gestational Diabetes
Authors: Dario Pitocco, Mauro Di Leo, Antonio Lanzone
Journal: JAMA Pediatrics (2019)

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
Abstract 18007: A Novel Cell Penetrating Peptide, Cardiac Targeting Peptide, Appears to Utilize Cardiac Channels for Transduction
Authors: Timothy Feinstein, Cecilia W Lo, Maliha Zahid
Journal: Circulation (2016)

Background: Cell penetrating peptides (CPP) are small peptides able to carry cargo across cellular membranes resulting in internalization of the intact cargo. Our prior work led to identification o...
Precision identification of high-risk phenotypes and progression pathways in severe malaria without requiring longitudinal data
Authors: Iain G. Johnston, Till Hoffmann, Sam F. Greenbury, Ornella Cominetti, Muminatou Jallow, Dominic Kwiatkowski, Mauricio Barahona, Nick S. Jones, Climent Casals-Pascual
Journal: npj Digital Medicine (2019)

More than 400,000 deaths from severe malaria (SM) are reported every year, mainly in African children. The diversity of clinical presentations associated with SM indicates important differences in disease pathogenesis that require specific treatment, and this clinical heterogeneity of SM remains poorly understood. Here, we apply tools from machine learning and model-based inference to harness large-scale data and dissect the heterogeneity in patterns of clinical features associated with SM in 2904 Gambian children admitted to hospital with malaria. This quantitative analysis reveals features predicting the severity of individual patient outcomes, and the dynamic pathways of SM progression, notably inferred without requiring longitudinal observations. Bayesian inference of these pathways allows us assign quantitative mortality risks to individual patients. By independently surveying expert practitioners, we show that this data-driven approach agrees with and expands the current state of knowledge on malaria progression, while simultaneously providing a data-supported framework for predicting clinical risk.
Abstract 11773: Anatomical Characteristics of Mitral Isthmus Requiring Ablation inside the Coronary Sinus for Creation of Complete Linear Block in Patients with Atrial Fibrillation
Authors: Hiroshi Hayashi, Yasushi Miyauchi, Meiso Hayashi, Kenji Yodogawa, Tsutomu Horie, Hiroshige Murata, Shunsuke Uetake, Ippei Tsuboi, Kenta Takahashi, Takao Kato, Kyoichi Mizuno
Journal: Circulation (2012)

Introduction: Creating a block line at the mitral isthmus (MI) is associated with a favorable outcome of catheter ablation for atrial fibrillation. However, radiofrequency energy delivery inside th...
Retrospective cohort study of 925 OAGB procedures. The UK MGB/OAGB collaborative group
Authors: A. Hussain, M. Van den Bossche, D.D. Kerrigan, A. Alhamdani, C. Parmar, S. Javed, C. Harper, J. Darrien, R. Singhal, S. Yeluri, P. Vasas, S. Balchandra, S. El-Hasani
Journal: International Journal of Surgery (2019)
Oncolytic Maraba virus armed with tumor antigen boosts vaccine priming and reveals diverse therapeutic response patterns when combined with checkpoint blockade in ovarian cancer
Authors: A. J. Robert McGray, Ruea-Yea Huang, Sebastiano Battaglia, Cheryl Eppolito, Anthony Miliotto, Kyle B. Stephenson, Amit A. Lugade, Gill Webster, Brian D. Lichty, Mukund Seshadri, Danuta Kozbor, Kunle Odunsi
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Cancer immunotherapies are emerging as promising treatment strategies for ovarian cancer patients that experience disease relapse following first line therapy. As such, identifying strategies to bolster anti-tumor immunity and limit immune suppression, while recognizing diverse patterns of tumor response to immunotherapy is critical to selecting treatment combinations that lead to durable therapeutic benefit. <h3>Methods</h3> Using a pre-clinical mouse model, we evaluated a heterologous prime/boost vaccine in combination with checkpoint blockade to treat metastatic intraperitoneal ovarian cancer. Vaccine-elicited CD8<sup>+</sup> T cell responses and changes in the tumor microenvironment following treatment were analyzed and compared to treatment outcome. Kinetics of intraperitoneal tumor growth were assessed using non-invasive magnetic resonance imaging (MRI). <h3>Results</h3> Vaccine priming followed by antigen-armed oncolytic Maraba virus boosting elicited robust tumor-specific CD8<sup>+</sup> T cell responses that improved tumor control and led to unique immunological changes in the tumor, including a signature that correlated with improved clinical outcome of ovarian cancer patients. However, this treatment was not curative and T cells in the tumor microenvironment (TME) were functionally suppressed. Combination PD-1 blockade partially overcame the adaptive resistance in the tumor observed in response to prime/boost vaccination, restoring CD8<sup>+</sup> T cell function in the TME and enhancing the therapeutic response. Non-invasive MRI of tumors during the course of combination treatment revealed heterogeneous radiologic response patterns following treatment, including pseudo-progression, which was associated with improved tumor control prior to relapse. <h3>Conclusions</h3> Our findings point to a key hierarchical role for PD-1 signaling and adaptive immune resistance in the ovarian TME in determining the functional fate of tumor-specific CD8<sup>+</sup> T cells, even in the context of robust therapy mediated anti-tumor immunity, as well as the ability of multiple unique patterns of therapeutic response to result in durable tumor control.