tbuckley/cabot-search huggingface dataset:
Abstract B47: Mutation of K104 abrogates the oncogenic properties of K-RasG12D
Authors: Moon Hee Yang, Bethany Hunt, Christian Johnson, Dhirendra Simanshu, Kevin Haigis
Journal: Cancer Research (2020)

Abstract Ras proteins function as small GTPases to regulate a wide range of cellular processes. The activity of Ras is dependent on its nucleotide-binding status, which is modulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Previously, we demonstrated that mutation of K104 to glutamine (K104Q) attenuates the transforming capacity of ectopic oncogenic K-Ras by interrupting GEF-induced nucleotide exchange. In order to assess the biologic relevance of this mutation in vivo, we used CRISPR/Cas9 to generate mouse models carrying the K104Q point mutation in wild-type and conditional K-RasLSL-G12D alleles. Animals homozygous for K104Q were viable, fertile, and arose at Mendelian frequency, indicating that K104Q is not a complete loss-of-function mutation. Consistent with our previous findings from in vitro studies, however, the oncogenic activity of K-RasG12D was significantly attenuated by mutation at K104. These data demonstrate that lysine at position 104 is critical for the full oncogenic activity of mutant K-Ras and suggest that modification at K104, for example acetylation, may also regulate its activity. Using biochemical and structural analysis, we found that the G12D and K104Q mutations cooperate to suppress GEF-mediated nucleotide exchange, explaining the preferential effect of K104Q on oncogenic K-Ras. Finally, we discovered an allosteric regulatory network consisting of K104 and residues on switch II that is key for regulating the stability of the switch II alpha helix. Given the high frequency of KRAS mutations in human cancers, modulation of this network may provide a unique therapeutic approach. Citation Format: Moon Hee Yang, Bethany Hunt, Christian Johnson, Dhirendra Simanshu, Kevin Haigis. Mutation of K104 abrogates the oncogenic properties of K-RasG12D [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B47.
Abstract 13281: Effect of Arteriovenous Anastomosis on Blood Pressure Reduction in Patients With Isolated Systolic Hypertension Compared to Combined Hypertension
Authors: Christian Ott, Mel D Lobo, Paul A Sobotka, Felix Mahfoud, Roland Schmieder
Journal: Circulation (2015)

Background: Several interventional therapeutic options for blood pressure (BP) lowering in patients with treatment-resistant hypertension (TRH) were introduced, such as renal denervation (RDN) and creation of an arteriovenous (AV) anastomosis using the ROX coupler. It was shown that BP response after RDN is greater in patients with combined hypertension (CH) compared to patients with isolated systolic hypertension (ISH). We analyzed now the effect of ROX coupler implantation in the subgroups with CH and ISH. Methods: The randomized, controlled, ROX CONTROL HTN study included patients with true TRH (office systolic BP ≥140mmHg, and average daytime ambulatory BP ≥135/85mmHg, despite treatment with at least 3 antihypertensive drugs including a diuretic). In our post-hoc analysis we have stratified the patients of the ROX coupler group (n=42) according CH (n=31) versus ISH (n=11). Results: Baseline systolic office (177±18 versus 169±17 mmHg, p=0.163) and ambulatory BP (159±16 versus 154±11 mmHg, p=0.463) did not differ between CH and ISH. Creation of an AV anastomosis resulted in a significant reduction in systolic office (CH: -28±22 versus ISH: -22±31 mmHg, p=0.572) as well as ambulatory BP (CH: -14±20 versus ISH: -13±15 mmHg, p=0.672), but without significant differences between the two subgroups. The non-responder rate (systolic office BP reduction &lt; 10 mmHg) after 6 months was not different between the subgroups (CH: 18 % versus ISH: 23 %, p=0.844). Conclusions: Thus, our data suggest that creation of an AV anastomosis using the ROX coupler reduces systolic office and ambulatory BP, without any significant difference between CH and ISH. In contrast to RDN, creation of an AV anastomosis reduced BP to similar extent in both subtypes of TRH.
Abstract 16462: PET-MRI of LAA Thrombus in Patients With Atrial Fibrillation Using a Novel Fibrin-Binding Radiotracer
Authors: David Izquierdo-Garcia, Anne Philip, Rory B Weiner, Moussa Mansour, Ciprian Catana, Peter Caravan, David E Sosnovik
Journal: Circulation (2019)

Background: The detection of LAA thrombus is usually performed using transesophageal echo (TEE). However, TEE is semi-invasive with limited anatomical coverage. We recently developed a PET-detectab...
What Does My Stage of Cancer Mean?
Authors: Aisha Patel, Howard (Jack) West
Journal: JAMA Oncology (2020)

What Does My Stage of Cancer Mean? Stage of CancerOnce a cancer is diagnosed, it needs to be carefully measured in both its size and extent of spread.This is classified through staging.The main factors affecting the stage of a cancer are the size of the primary tumor (where the cancer started), the involvement of lymph nodes, and the potential spread to other organs in the body.Various cancers are staged differently based on the cancer's pattern of advancement, how quickly it tends to spread, and where it travels within the body.Staging is commonly done through a physical examination, imaging studies, and sometimes additional biopsies.Staging can be done on various scales, most commonly the TNM staging and a scale of I to IV.
Waiting for Certainty on Covid-19 Antibody Tests — At What Cost?
Authors: Milton C. Weinstein, Kenneth A. Freedberg, Emily P. Hyle, A. David Paltiel
Journal: New England Journal of Medicine (2020)

Waiting for Certainty on Covid-19 Antibody Tests Despite our inability to guarantee the accuracy of an immunity-certification process, failing to take action to identify people who could safely ret...
Abstract A56: Identification of circulating miRNA signatures in rectal cancer
Authors: Klara Cervena, Alena Opattova, Barbara Pardini, Alessio Naccarati, Pavel Vodicka, Veronika Vymetalkova
Journal: Clinical Cancer Research (2020)

Abstract Colorectal cancer is the third most common cancer and the second leading cause of cancer death in Europe. Therefore, the search for new biomarkers to enable facilitate early diagnosis, prognosis, and individualized treatment is particularly warranted. From a clinical point of view, malignancies in the colon and the rectum (RC) present two distinct entities that require different treatment strategies, so CRC might not be considered as a single enteropathogenic entity. MicroRNA (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. The discovery that miRNAs may act either as oncogenes or tumor suppressors has initiated extensive research. It was recently discovered that extracellular miRNAs circulate in the bloodstream and that such circulating miRNAs are remarkably stable. This has raised the possibility that miRNAs might serve as novel markers for disease diagnosis and prognosis. In the present study, we aimed to identify circulating miRNAs enabling early diagnosis and prognosis of RC. MiRNA expression levels (from plasma and plasma exosomes) were characterized by next-generation sequencing (NGS) in 24 patients with RC collected at 2-time intervals. The first sampling was collected at the time of diagnosis and the second sampling was conducted around 1 year after the diagnosis. The expression levels of miR-122 and miR-142 were identified to be associated with overall survival in RC patients. Their functional characteristics were tested in vitro on rectal cancer cell lines HRA16 and SW1463. Increased levels of miRNAs were associated with decreased long-term survival of cells. Identified miRNAs are currently being verified on a larger population of RC patients. This has raised the question whether miRNA can serve as biomarkers for rectal cancer, but prior to its clinical applications, clinical trials are warranted. Acknowledgments: This work was supported by AZV 17-30920A, GA17-16857S, and GA UK 302119. Citation Format: Klara Cervena, Alena Opattova, Barbara Pardini, Alessio Naccarati, Pavel Vodicka, Veronika Vymetalkova. Identification of circulating miRNA signatures in rectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A56.
An Early Result Acceptance Program for Residency Application—Reply
Authors: Maya M. Hammoud, John S. Andrews, Susan E. Skochelak
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients
Authors: E Tuaillon, K Bolloré, A Pisoni, S Debiesse, C Renault, S Marie, S Groc, C Niels, N Pansu, AM Dupuy, D Morquin, V Foulongne, A Bourdin, V Le Moing, P Van de Perre
Journal: Journal of Infection (2020)
Incidental Discovery of a COVID-19 Infection on a Reevaluation FDG PET/CT in a Patient Treated for Hodgkin Lymphoma
Authors: Celestine Simand, Caroline Bund, Blandine Guffroy, Vitaliy Chaban, Raoul Herbrecht
Journal: Clinical Nuclear Medicine (2020)

Abstract We report the results of 18 F-FDG PET/CT in an asymptomatic case of COVID-19 infection. A 27-year-old woman underwent FDG PET/CT for revaluation of a stage IIIE B Hodgkin lymphoma after the fourth cycle of chemotherapy. It showed intense avid FDG subpleural mixed ground-glass and consolidative lesions, especially in the left lung. Because of this morpho-metabolic aspect and the epidemic context, a viral pneumopathy was suspected. The patient who was initially asymptomatic was admitted for fever 28 hours after the PET/CT. The nasopharyngeal swab was positive for COVID-19, and the outcome was favorable.
The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs
Authors: Lele Zhang, Chaofeng Hou, Chen Chen, Yaxin Guo, Weitang Yuan, Detao Yin, Jinbo Liu, Zhenqiang Sun
Journal: Molecular Cancer (2020)

N6-methyladenosine (m6A), the most abundant modification in eukaryotic cells, regulates RNA transcription, processing, splicing, degradation, and translation. Circular RNA (circRNA) is a class of covalently closed RNA molecules characterized by universality, diversity, stability and conservatism of evolution. Accumulating evidence shows that both m6A modification and circRNAs participate in the pathogenesis of multiple diseases, such as cancers, neurological diseases, autoimmune diseases, and infertility. Recently, m6A modification has been identified for its enrichment and vital biological functions in regulating circRNAs. In this review, we summarize the role of m6A modification in the regulation and function of circRNAs. Moreover, we discuss the potential applications and possible future directions in the field.
IMpower, CASPIAN, and more: exploring the optimal first-line immunotherapy for extensive-stage small cell lung cancer
Authors: Chengliang Huang, Gregory N. Gan, Jun Zhang
Journal: Journal of Hematology & Oncology (2020)

Abstract The life expectancy of extensive-stage small cell lung (ES-SCLC) cancer patients has not improved in the last 2–3 decades until two recent trials (CASPIAN and IMpower133) showing the addition of anti-programmed death ligand (PD-L1) therapy to chemotherapy has survival benefit over chemotherapy alone. However, such benefit is relatively small and was not even observed in some other trials using immunotherapy, raising the question of optimal chemoimmunotherapy combination in the 1st-line setting for ES-SCLC. Here, we discussed several thought-provoking questions with the focus on IMpower133 and CASPIAN trials.
Author Correction: Cxcl10+ monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation
Authors: Amir Giladi, Lisa Katharina Wagner, Hanjie Li, Dorothea Dörr, Chiara Medaglia, Franziska Paul, Anat Shemer, Steffen Jung, Simon Yona, Matthias Mack, Achim Leutz, Ido Amit, Alexander Mildner
Journal: Nature Immunology (2020)
Long-Term Survival of Patients with Chronic Phase Chronic Myeloid Leukemia Who Received Autologous Stem Cell Transplantation and Further Exposed to Tyrosine Kinase Inhibitors. a Study on Behalf of the French Society of Blood and Marrow Transplantation and the French Group of CML
Authors: Mauricette Michallet, Mohamad Sobh, Aude Charbonnier, Eric Deconinck, Viviane Dubruille, Valerie Coiteux, Martine Delain, Francoise Huguet, Delphine Rea, Dominique Bron, Nicole Raus, Alain Jacques Delmer, Pascal Lenain, Noel Milpied, Francois-Xavier Mahon, Franck Emmanuel Nicolini, Gabriel Etienne
Journal: Blood (2017)
Incidental COVID-19 Pneumonia on 18F-Fluorocholine PET/CT
Authors: Ana María García Vicente, Ángel Soriano Castrejón
Journal: Clinical Nuclear Medicine (2020)

Abstract We present the case of a patient who underwent 18 F-fluorocholine PET/CT for biochemical recurrence of prostate cancer in which bilateral pneumonia was diagnosed. In the current state of COVID-19 pandemic, a high prevalence of incidental pneumonia may be expected, even with previous clinical triage, explained by a nondefined number of patients who were asymptomatic or minimally symptomatic for infectious process. Therefore, nuclear medicine physicians should be prepared to recognize and diagnose incidental COVID-19 pneumonia manifestation on 18 F-fluorocholine PET/CT, due to the crucial epidemiological implications.
Abstract 439: Using the Time Interval Between R-Wave Detection and Maximum Compression Pressure to Target and Validate Delivery of Synchronized Chest Compressions During Pseudo Electro-Mechanical Dissociation
Authors: Joshua W Lampe, Jeff R Gould, Karen L Moodie, Zachary P Soucy, Peter S Burrage, Norman A Paradis
Journal: Circulation (2019)

Introduction: The treatment of pseudo electro-mechanical dissociation (P-EMD) with standard chest compressions leads to some compressions that interfere with blood flow created by ventricular contraction and others that are synergistic. We have previously reported that the hemodynamics generated by standard chest compressions (StdCPR) depended on the time interval between the R-wave and the maximum compression pressure (t_int). Our goal was to use the t_int to identify the optimal timing for compression synchronization and to validate the delivery of synchronized chest compressions. Methods: Eight animals underwent surgical preparation and were exposed to hypoxia to induce P-EMD. The treatment period was divided into eight 45 sec epochs during which the P-EMD was left untreated or was treated with StdCPR or chest compressions synchronized to the R-wave in the ECG (SyncCPR). For each heart beat t_int was calculated as t peak AOP - t Rwave , blood pressures were averaged, and blood flows were integrated. 1,598 chest compressions were analyzed. The location of local extrema in hemodynamic parameters as a function of positive t_int values were identified recursively by dividing the range of t_int values into increasing numbers of bins and determining which bin had the highest mean value. Results: Blood flows and pressures exhibited a non-linear dependence on t_int. The maximum CPP occurred at t_int = 90 ±2.3 ms. The maximum aortic pressure occurred at t_int = 70 ±2.3 ms. The minimum right atrial pressure occurred at t_int = 280 ±2.3 ms. The maximum carotid blood flow occurred at t_int = 100 ±2.3 ms. The maximum jugular blood flow occurred at t_int = 400 ±2.3 ms. Unsynchronized chest compressions resulted in a t_int of -21 ± 170 ms. Synchronized chest compressions resulted in a t_int of 119 ± 13 ms. Conclusions: Local maxima and minima during StdCPR were identified in several hemodynamic parameters, but the extrema were not perfectly co-located. It appears that a t_int of 90-100 ms could be optimal. SyncCPR were delivered at 119 ms, which is not far from the local maxima observed for CPP and carotid blood flow.
Memory trace interference impairs recall in a mouse model of Alzheimer’s disease
Authors: Stefanie Poll, Manuel Mittag, Fabrizio Musacchio, Lena C. Justus, Eleonora Ambrad Giovannetti, Julia Steffen, Jens Wagner, Lioba Zohren, Susanne Schoch, Boris Schmidt, Walker S. Jackson, Dan Ehninger, Martin Fuhrmann
Journal: Nature Neuroscience (2020)
Abstract B17: Modeling genomic complexity of colorectal cancer using multigenic <i>Drosophila</i> models
Authors: Sindhura Gopinath, Ross Cagan, Eric Schadt
Journal: Cancer Research (2020)

Abstract Colorectal cancer (CRC) is a leading cause of cancer related death worldwide, with an estimated 53,000 deaths in 2019 in the US alone. Despite significant progress made in elucidating mechanisms of tumor initiation and progression, targeted therapies have shown limited efficacy for inoperable or metastatic CRC tumors, especially KRAS or BRAF mutant tumors, which account for more than half (~55%) of CRC tumors. Several targeted inhibitors have failed clinical trials for CRC despite proving effective in preclinical CRC studies and other cancer types. A potential reason for this resistance is the presence of several other mutations in the tumors. CRC patient tumors present significant genetic heterogeneity with mutations in genes in several other major signaling pathways. We address the challenge of genetic complexity by constructing a population of multigenic Drosophila CRC models incorporating 7-15 gene alterations in each line. This population of CRC fly lines models the genetic heterogeneity of CRC by basing the genotype of each fly line on an individual patient’s tumor genotype, with a focus on Ras mutant tumors. Our work has identified multiple combinations of FDA-approved compounds that have shown efficacy in some complex multigenic models and not others. Bangi et al. (2019) discuss the results from the first human CRC patient to be treated with the recommended combination identified from screening the patient-matched fly model. My work aims to uncover the mechanisms of response and resistance presented by the population of heterogeneous CRC genotypes. My results show that there is variability in therapeutic response between different patient genotypes, even when they contain the same known CRC cancer drivers (such as Ras, p53, APC, etc.). I am investigating the downstream transcriptional and signaling networks activated by these genotypes to assess their contribution to resistance or response to specific therapeutic agents. Citation Format: Sindhura Gopinath, Ross Cagan, Eric Schadt. Modeling genomic complexity of colorectal cancer using multigenic Drosophila models [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B17.
Interventions supporting long term adherence and decreasing cardiovascular events after myocardial infarction (ISLAND): pragmatic randomised controlled trial
Authors: Noah M Ivers, Jon-David Schwalm, Zachary Bouck, Tara McCready, Monica Taljaard, Sherry L Grace, Jennifer Cunningham, Beth Bosiak, Justin Presseau, Holly O Witteman, Neville Suskin, Harindra C Wijeysundera, Clare Atzema, R Sacha Bhatia, Madhu Natarajan, Jeremy M Grimshaw
Journal: BMJ (2020)

Abstract Objective To test a scalable health system intervention to improve long term adherence to secondary prevention treatments among patients who have had a recent myocardial infarction. Design Three arm, pragmatic randomised controlled trial with blinded outcome assessment. Setting Nine cardiac centres in Ontario, Canada. Participants 2632 patients with obstructive coronary artery disease after a myocardial infarction, identified from a centralised cardiac registry. Interventions Participants were randomised 1:1:1 to receive usual care, five mail-outs developed through a user centred design process, or mail-outs plus phone calls. The phone calls were delivered first by an interactive automated system to screen for non-adherence to treatment. Trained lay health workers followed up as necessary. Interventions were coordinated centrally but delivered from each patient’s hospital site. Main outcome measures Co-primary outcomes were completion of cardiac rehabilitation and adherence to recommended medication. Data were collected by blinded assessors through patient report and from administrative health databases at 12 months. Results 2632 patients (mean age 66, 71% male) were randomised: 878 to the full intervention (mail plus phone calls), 878 to mail only, and 876 to usual care. Of the respondents, 174 (27%) of 643 in the usual care group, 200 (32%) of 628 in the mail only group, and 196 (37%) of 531 allocated to the full intervention completed cardiac rehabilitation (adjusted odds ratio 1.55, 95% confidence interval 1.18 to 2.03). In the mail plus phone group, 11.7%, 6.0%, 14.4%, 32.9%, and 35.0% reported adherence to 0, 1, 2, 3, and 4 drug classes after one year, respectively, in comparison with 12.5%, 6.8%, 13.6%, 30.2%, and 36.8% in the mail only group, and 12.2%, 8.4%, 13.1%, 30.3%, and 36.1% in the usual care group, respectively (mail only v usual care, odds ratio 0.98, 95% confidence interval 0.81 to 1.19; full intervention v usual care, 0.99, 0.82 to 1.20). Conclusions Scalable interventions delivered by mail plus phone can increase completion of cardiac rehabilitation after myocardial infarction but not adherence to medication. More intensive interventions should be tested to improve adherence to medication and to evaluate the association between attendance at cardiac rehabilitation and adherence to medication. Trial registration ClinicalTrials.gov NCT02382731 , registered 9 March 2015 before any patient enrolment.