tbuckley/cabot-search huggingface dataset:
TMIC-35. IDH1 MUTATION IN GLIOMA REPROGRAMS EARLY MYELOID DIFFERENTIATION IN THE BONE MARROW (BM) TO PRODUCE NON-IMUNESUPPRESSIVE NEUTROPHILS
Authors: Mahmoud Alghamri, Maria Castro, Pedro Lowenstein, Neha Kamran, Padma Kadiyala, Ruthvik Avvari, Li Zhang
Journal: Neuro-Oncology (2019)

Abstract Gliomas are the most common primary brain tumors; patients exhibit a poor prognosis. Mutations in isocitrate dehydrogenase (mIDH) are present in most patients with lower grade glioma (LGG), and are correlated with better prognosis and survival. We postulated that mIDH1 induces epigenetic reprogramming leading to alteration in immune cells’ function. To examine the role of mIDH1 in the tumor immune microenvironment (TME), we generated LGG glioma models using the sleeping beauty system (Koschmann et al., 2016, Nunez et al., 2019). We show that mIDH1 gliomas exhibit increased levels of CD11b+ Gr1+ myeloid derived suppressor cells in the tumor, BM, circulation and spleen of mice. We found that mIDH1 modifies the cytokines’ repertoire in the glioma microenvironment altering the phenotype and function of the tumor infiltrating CD45+/CD11b+/Gr-1+ myeloid cells, rendering them non-immunosuppressive. Production of these cells results from activation of the granulocytic differentiation program in the BM. This novel mechanism is mediated by tumor-derived granulocyte-colony stimulating factor (G-CSF) which elicits expansion and differentiation of hematopoietic stem cells, skewing hematopoiesis towards the immature myeloid lineage. Moreover, mIDH1 glioma derived G-CSF causes mobilization of hematopoietic stem cells (HSCs) and myeloid progenitors (MPs) from BM to spleen. Blocking G-CSF in mIDH1 bearing mice significantly restored HSCs, and MPs frequencies in the spleen to levels encountered in wtIDH1 glioma. Interestingly, blocking G-CSF restored the inhibitory function of the granulocytic CD11b+ Gr-1+ in mIDH1, and shortened the median survival (MS) of mIDH1 bearing mice to the same MS encountered in wtIDH1 glioma. Our results provide insights into novel epigenetic alterations triggered by mIDH1 which regulate myeloid cells’ heterogeneity and immunosuppression; a feature that can be harnessed to develop novel immunotherapeutic strategies.
Atherosclerotic Vascular Disease Conference
Authors: Sidney C. Smith, Richard V. Milani, Donna K. Arnett, John R. Crouse, Mary McGrae McDermott, Paul M Ridker, Robert S. Rosenson, Kathryn A. Taubert, Peter W.F. Wilson
Journal: Circulation (2004)

T he current understanding of risk factors for atheroscle- rotic vascular disease (AVD) embodies extrapolation of information derived from the traditional risk factors for atherosclerotic coronary disease, application of emerging novel risk factors, and study of new genetic mechanisms.
Author's reply
Authors: J. Belch
Journal: BMJ (2008)

<h3>Abstract</h3> Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) mRNA vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of literature was performed and a total of 18 studies (<i>N</i>=15,980) were identified and reviewed. The percent difference of means of reported antibody titers were then calculated to determine the decline in humoral response after the peak levels post-vaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6 months post-vaccination. Additionally, results showed that regardless of age, sex, serostatus and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain (RBD) IgG and anti-spike IgG, ranging from 94-95% at 90-180 days and 55-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns (VoCs).
TEM-MM-101: A Phase I/IIa Dose Escalation Study Evaluating the Safety and Activity of Autologous CD34+ Enriched Hematopoietic Progenitor Cells Genetically Modified for Human Interferon-α2 in Multiple Myeloma Patients with Early Relapse after Intensive Front Line Therapy
Authors: Bernhard Gentner, Francesca Farina, Matteo Giovanni Carrabba, Magda Marcatti, Stefania Girlanda, Gabriele Antonarelli, Capotondo Alessia, Stefania Mazzoleni, Carlo Russo, Luigi Naldini, Fabio Ciceri
Journal: Blood (2019)
Abstract #1428: DNA methylation profiles are associated with specific genome-wide copy number alteration profiles in head and neck squamous cell carcinoma
Authors: Graham Poage, Brock Christensen, Carmen Marsit, E.Andres Houseman, Margaret Wrensch, Margaret Karagas, Ru-Fang Yeh, Heather Nelson, Joseph Wiemels, Shichun Zheng, Marshall Posner, Michael McClean, John Wiencke, Karl Kelsey
Journal: Cancer Research (2009)

The dysregulation of gene expression, indispensible for cellular transformation, is controlled by a range of underlying molecular mechanisms, including allelic imbalance, copy number variation (CNV) and epigenetic alterations. In fact, CNV and epigenetic alterations (such as aberrant DNA methylation) are often commonplace in human tumors due to their associated selective survival and proliferation advantages. However, the relationship between CNV and DNA methylation alteration in cancer remains poorly studied. In order to directly compare these forms of somatic alterations, we first performed genome-wide analyses in a case series of head and neck squamous cell carcinomas (HNSCCs) using the Affymetrix GeneChip® Human Mapping 500K gene array to investigate CNV in 19 matched tumor-blood samples. Next, we examined DNA methylation alterations using the Illumina GoldenGate cancer methylation panel of CpG dinucleotide loci on 68 HNSCCs, including the 19 samples assayed for CNV. Unsupervised clustering of the methylation data using a recursively-partitioned mixture model yielded six distinct methylation profile classes. Strikingly, the overall amount of copy number variation was found to vary significantly according to modeled methylation class, with tumors showing substantial, large-scale copy number variation segregating into separate classes. Specifically, all tumors that possessed chromosome 8p loss and 8q reduplication (n=7) were members of one methylation class. Plotting CNV profiles in a methylation-class-specific manner for chromosome 8, we were able to explore the locus-specific relationships between methylation alterations and CNV. Although some chromosome 8 genes had increased methylation in the amplified 8q arm, in general, chromosome 8 genes tended not to have differential methylation associated with CNV. Our results demonstrate that there is a significant relationship between methylation profiles of cancer-related genes and CNV in HNSCC, although the timing of these transformational events is less clear. Additional investigations in HNSCC and other cancers using integrative genomics approaches are necessary, and hold promise for significantly advancing our understanding of tumor biology and thereby, the potential to reveal key targets for novel, directed therapeutic approaches.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1428.
Integrated Systems Level Examination of Proteasome Inhibitor Stress Recovery in Myeloma Cells Reveals Druggable Vulnerabilities Linked to Multiple Metabolic Processes
Authors: Paula Saavedra-Garcia, Hibah A Al-Sadah, Lucy Penfold, Xiaobei Xiong, Elena Lopez-Jimenez, Katarzyna Parzych, Valentina S Caputo, Kevin Blighe, Martin F. Kaiser, Paolo Piazza, Vesela Encheva, Ambrosius P Snijders, Hector C Keun, Diego Oyarzun, Denise Thiel, Zijing Liu, Mauricio Barahona, Holger W Auner
Journal: Blood (2019)
MNGI-06. EFFICACY OF 177LU-DOTATATE THERAPY IN RECURRENT ANAPLASTIC MENINGIOMA
Authors: Sani Kizilbash, Derek Johnson
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND 177Lu-Dotatate (177Lu-DOTA0-Tyr3-Octreotate) is a beta-particle emitting somatostatin analog recently FDA approved for the treatment of somastatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Somatostatin receptors are highly expressed in almost all meningiomas, therefore 177Lu-Dotatate may be a reasonable treatment strategy for this disease. Furthermore, the short path length of the beta particle should allow for treatment of previously radiated patients with low risk of cerebral radiation necrosis. CASE STUDY: A 61 year-old male presented with a history of atypical meningioma (WHO grade II), recurrent as anaplastic meningioma (WHO grade III). His previous treatments included multiple surgical resections, fractionated radiation therapy, stereotactic radiosurgery, everolimus/octreotide LAR, bevacizumab and hydroxyurea. MRI imaging revealed rapid volumetric progression over the prior nine months with a near tripling in size from 29.9 cm3 to 80.4 cm3. In-111 octreotide confirmed the presence of somatostatin receptors within the tumor. 177Lu-Dotatate was administered intravenously at a dose of 200 millicuries per dose, every eight weeks for four cycles. Treatment was tolerated very well, with no significant adverse events. Tumor volume initially increased to 98.3 cm3 after cycle 1 of treatment, and subsequently decreased to 91.2 cm3 after cycle 2. Eight months after treatment onset, the tumor volume remained stable (93.4 cm3). CONCLUSION 177Lu-Dotatate may be a safe and effective strategy for the treatment of somastatin receptor-positive meningioma. The transient increase in tumor volume after the first dose in this case may have represented delayed treatment effect or pseudoprogression. A phase II clinical trial is currently being activated to determine the progression-free survival associated with 177Lu-Dotatate in patients with recurrent meningioma.
Survival Outcomes Following Allogeneic Stem Cell Transplantation for Inherited Bone Marrow Failure and Myeloid Germline Predisposition Syndromes
Authors: Kalyan Nadiminti, Abhishek A Mangaonkar, Kimberly J. Langer, Shakila P Khan, Vilmarie Rodriguez, Naseema Gangat, Michelle A Elliott, Hassan B. Alkhateeb, Mithun Vinod Shah, Mark Litzow, William J Hogan, Saad S. Kenderian, Mrinal M Patnaik
Journal: Blood (2019)
Impact of Post-Transplant Consolidative Radiotherapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma and a PET-CT Based Predictive Model for Relapse
Authors: Collin Chin, Andrew Wirth, David Ritchie, Michael Hofman, Michael MacManus, John F. Seymour, Belinda Campbell, Michael Dickinson
Journal: Blood (2019)
Impact of Comorbidities on Survival of Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors
Authors: Fernanda F Engelbrecht, Eliana C Miranda, Marcia Torresan Delamain, Gislaine Borba Duarte, Carmino Antonio Souza, Erich V De Paula, Katia B Pagnano
Journal: Blood (2019)
Inflammatory Cytokine Responsive Enzymatic Mutagenesis Fuels Myeloproliferative Neoplasm Pre-Leukemia Stem Cell Evolution
Authors: Catriona Jamieson, Qingfei Jiang, Frida Holm, Jane Isquith, Adam Mark, Cayla Mason, Wenxue Ma, Raymond H Diep, Jessica Pham, Eduardo Reynoso Moreno, Chanond A Nasamran, Xu Guorong, Amanda Birmingham, Leslie A Crews, Ludmil Alexandrov, Gabriel Pineda, Thomas Whisenant, Kathleen M Fisch
Journal: Blood (2019)
Differential DNA methylation in bronchial biopsies between persistent asthma and asthma in remission
Authors: Cornelis J. Vermeulen, Cheng-Jian Xu, Judith M. Vonk, Nick H.T. ten Hacken, Wim Timens, Irene H. Heijink, Martijn C. Nawijn, Jeunard Boekhoudt, Antoon J. van Oosterhout, Karen Affleck, Markus Weckmann, Gerard H. Koppelman, Maarten van den Berge
Journal: European Respiratory Journal (2019)

Approximately 40% of asthmatics experience remission of asthma symptoms. A better understanding of biological pathways leading to asthma remission may provide insight into new therapeutic targets for asthma. As an important mechanism of gene regulation, investigation of DNA methylation provides a promising approach. Our objective was to identify differences in epigenome wide DNA methylation levels in bronchial biopsies between subjects with asthma remission and subjects with persistent asthma or healthy controls. We analysed differential DNA methylation in bronchial biopsies from 26 subjects with persistent asthma, 39 remission subjects and 70 healthy controls, using the limma package. The comb-p tool was used to identify differentially methylated regions. DNA methylation of CpG-sites was associated to expression of nearby genes from the same biopsies to understand function. Four CpG-sites and 42 regions were differentially methylated between persistent asthma and remission. DNA methylation at two sites was correlated i n cis with gene expression at ACKR2 and DGKQ . Between remission subjects and healthy controls 1163 CpG-sites and 328 regions were differentially methylated. DNA methylation was associated with expression of a set of genes expressed in ciliated epithelium. CpGs differentially methylated between remission and persistent asthma identify genetic loci associated with resolution of inflammation and airway responsiveness. Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls.
First Line Treatment with Venetoclax and Ibrutinib Induction Followed By Obinutuzumab Intensification Exclusively in CLL/SLL Patients Not in Complete Remission and/or with Detectable Bone Marrow Minimal Residual Disease (NEXT STEP trial)
Authors: Sabina Kersting, Mark-David Levin, Carsten Utoft Niemann, Yvette Norden, Arnon P. Kater
Journal: Blood (2019)
QOLP-31. ASSESSING THE IMPACT OF GLIOBLASTOMA ON WORK PRODUCTIVITY IN PATIENTS AND THEIR CAREGIVERS
Authors: Terri Armstrong, Vinay Puduvalli, Tobias Walbert, Katherine Peters, Ashlee Loughan, Manmeet Ahluwalia, Paula Province Warren, David Cachia, Jennie Taylor, Jaishri O Blakeley, Arijit Ganguli, Nikhil Khandelwal, Rajesh Kamalakar, Les Noe, Priya Kumthekar
Journal: Neuro-Oncology (2019)

Abstract Information is limited on the impact of glioblastoma (GBM) on patient employment and caregiver time commitments. This observational multisite study evaluated the impact of GBM on patients’ employment and on caregivers’ ability to work and perform daily activities. A total of 180 adults diagnosed with GBM and their caregivers were stratified across 4 groups representing specific stages in the disease course: Group 1=newly diagnosed; 2=postradiation; 3=stable disease; 4=recurrence. We assessed the impact of GBM on employment status and self-reported cognitive function in patients (EORTC QLQ-C30) and in caregivers (Work Productivity and Activity Impairment Questionnaire). Prior to diagnosis, 64% of all patients (74% &lt; 65 years old) were employed, while only 22% (26% for those &lt; 65 years old) were employed after diagnosis. Though not reaching significance, newly diagnosed patients and those with stable disease reported higher mean cognitive function scores (72.0 and 71.9) than other groups (61.1 and 61.3; P=0.227). At study enrollment, 56% of all caregivers were employed, while 41% had left their jobs to care for their patients. The impact on caregiver work productivity varied with a higher percentage of caregivers of newly diagnosed patients and those with recurrent disease missing work (45% and 24%, respectively) and experiencing work impairment (54% and 36%, respectively) than the other groups (P&lt; 0.05). Forty-one percent of caregivers of newly diagnosed patients to 25% of patients with stable disease reported impairment of daily activities. GBM had a significant impact on patient and caregiver employment from the time of diagnosis. High cognitive burden among patients might have impacted their employment. Overall work and activity impairment for caregivers was evident in all groups with a notable impact at the time of first diagnosis and recurrence of disease. Future studies will explore the impact of these findings in a longitudinal cohort.
ALPHA PARTICLES AND PROTON BEAMS IN THERAPY
Authors: J DUFFY
Journal: JAMA (1963)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Dual Inhibition of MDM2 and XPO1 Synergizes to Induce Apoptosis in Acute Myeloid Leukemia Progenitor Cells with Wild-Type TP53 through Nuclear Accumulation of p53 and Suppression of c-Myc
Authors: Yuki Nishida, Jo Ishizawa, Vivian Ruvolo, Kensuke Kojima, Rafael Heinz Montoya, Naval G. Daver, Arnaud Lesegretain, Sharon Shacham, Michael Andreeff
Journal: Blood (2019)
A Humanitarian House Divided—Unifying Conflict Zone Humanitarian Surgical Care
Authors: Matthew J. Martin
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Exploring the Potential of Shallow Whole-Genome Sequencing for Diagnosis and Disease Monitoring of Lymphoma in Liquid Biopsy
Authors: Lennart Raman, Malaïka Van Der Linden, Ciel De Vriendt, Bliede Van Den Broeck, Kristoff Muylle, Dries Deeren, Bjorn Menten, Fritz Offner, Jo Van Dorpe
Journal: Blood (2019)
Real-World Utilization and Safety of Daratumumab Rapid Infusion Administered in a Community Setting: A Retrospective Observational Study
Authors: Lucio Gordon, Melody Chang, Marie-Hélène Lafeuille, Hela Romdhani, Faud Paramasivam, Xinmei Zhu, Sriya Gunawardena, Eric M Maiese
Journal: Blood (2019)
Mood and Dysfunctional Cognitions Constitute Within-Subject Antecedents and Consequences of Exercise in Eating Disorders
Authors: Markus Reichert, Sabine Schlegel, Friederike Jagau, Irina Timm, Lena Wieland, Ulrich W. Ebner-Priemer, Armin Hartmann, Almut Zeeck
Journal: Psychotherapy and Psychosomatics (2019)

Technological progress offers the chance to incorporate health interventions into everyday life, for example, on smartphones, which may be beneficial for people with mental illness. However, there is a large gap between what is technically feasible and what is known about effects on everyday life. For example, exercise is known to reduce depression symptoms in general, but specific influences of exercise interventions on everyday life mood, a core issue of depression, have yet to be studied. Therefore, we equipped 15 participants with depression with smartphone diaries for 3 days both before and after a 10-week exercise intervention. The participants answered 83.6% of all queries. Significant cross-level interaction effects in multilevel analyses revealed that people who engaged less in exercise at the start of the intervention showed greater improvements in everyday life mood (valence: b = 5.8; calmness: b = 5.3). Our results may serve as a tiny kick-off paving the way for evidence-based physical activity interventions on smartphones.
GP practices with more capitation funding get higher CQC ratings, study finds
Authors: Gareth Iacobucci
Journal: BMJ (2019)

General practices in England with higher capitation funding consistently received higher ratings in regulatory inspections by the Care Quality Commission over a three year period, a study has found.1 Higher capitation funding was associated with higher ratings across all areas measured by the CQC and in the overall rating that practices received, the research published in BMJ Open found.

The cross sectional study pooled three years of administrative data from 7310 practices (95% of the total) that underwent CQC inspections between November 2014 …