tbuckley/cabot-search huggingface dataset:
Autoimmune Hemolytic Anemia Confers Risk of Thromboembolism That Is Not Attributable to Usual Thrombosis Risk Factors: A Longitudinal, Retrospective Cohort Study Using the "Stride" Database
Authors: Evan C. Chen, Pooja D. Loftus, Susan C. Weber, Nhat Minh Hoang, James Gilbert, Shivaani Kummar
Journal: Blood (2016)
The Absolute Count of Circulating, Classical, CD14++/CD16- Monocytes Is a Poor Prognosis Marker in Chronic Myelomonocytic Leukemia (CMML)
Authors: Matthieu Jestin, Sihem Tarfi, Bouchra Badaoui, Nicolas Freynet, Ivan Sloma, Margot Morabito, Sébastien Maury, Pierre Fenaux, Eric Solary, Dorothée Selimoglu-Buet, Orianne Wagner Ballon
Journal: Blood (2019)
Can food allergy be cured? What are the future prospects?
Authors: Vanitha Sampath, Sayantani B. Sindher, Andres M. Alvarez Pinzon, Kari C. Nadeau
Journal: Allergy (2019)

Food allergies have become a significant heath burden as prevalence continues to rise, affecting 6%-13% of the global population. In the absence of drugs approved by regulatory agencies, the current standard of care remains avoidance of allergenic foods and management of acute allergic reactions with antihistamines and epinephrine autoinjectors. Allergen immunotherapy has been shown to increase the threshold of reactivity in the majority of food-allergic individuals. However, challenges include long treatment periods, high rates of adverse reactions, and lack of permanence of desensitization and established protocols. To address these limitations, adjunctive allergen-specific immunotherapy, vaccines, and non-allergen-specific therapies (eg, monoclonal antibodies) are being explored. The future of food allergy treatment is promising with a number of clinical trials in progress. Currently, although desensitization can be achieved for the majority of individuals with food allergy through immunotherapy, continued ingestion of allergen is needed for most individuals to maintain desensitization. Further understanding of the mechanisms of food allergy and identification of biomarkers to distinguish between temporary and permanent resolution of allergies is needed before a cure, where reactivity to the allergen is permanently lost enabling the individual to consume the allergen in any amount at any time, can be envisioned.
Organ preservation with daily concurrent chemoradiotherapy using a new superselective intra-arterial infusion for stage III, IV tongue cancer.
Authors: Iwai Tohnai, Kenji Mitsudo, Mitomu Kioi, Toshiyuki Koizumi, Senri Oguri, Toshinori Iwai, Makoto Hirota, Nobukazu Fuwa
Journal: Journal of Clinical Oncology (2012)

5556 Background: Combined radiotherapy and intra-arterial chemotherapy, which delivers a very high concentration of anticancer agent to the tumor, is currently used to treat advanced head and neck cancer. However, chemotherapy and radiotherapy cannot be performed simultaneously on a daily basis under conventional methods because long-term catheterization is not possible. Therefore, we developed a new method using superselective intra-arterial infusions via the superficial temporal artery and the occipital artery, and used it to perform daily concurrent chemoradiotherapy for the treatment of advanced tongue cancer. Methods: Seventy-two patients with advanced tongue cancer underwent chemoradiotherapy using this superselctive intra-arterial infusion method. Catheters were inserted superselectively to the feeding arteries of the tumor via the superficial temporal artery and the occipital artery. Long-term catheterization is possible in this method. Daily concurrent combined therapy with radiotherapy (total dose: 60 Gy), superselective intra-arterial chemotherapy using DOC (total dose: 60 mg/m 2 ) and CDDP (total dose: 150 mg/m 2 ) was performed. The anticancer agent was injected in a bolus through the intra-arterial catheter simultaneously with radiotherapy. Results: No major complications were observed. Clinical efficacy was CR in 64 (88.9 %) patients and PR in 8 (11.1 %). With a median follow-up period of 31 months (range 6 to 72 months), the overall survive rate was 74.8 % and the local control rate was 93.7%. Conclusions: This superselective intra-arterial infusion allows for long-term catheterization, unlike the conventional method, so that chemotherapy can be performed simultaneously with radiotherapy on a daily basis. This treatment method promises to be the strategy of choice for the treatment of advanced tongue cancer.
P2.15-C Phase 1 Trial Evaluating Safety, Efficacy, and PK of AMG 510, a Novel KRASG12C Inhibitor, in Non-Small Cell Lung Cancer
Authors: R. Govindan, M.G. Fakih, T.J. Price, G.S. Falchook, J. Desai, J.C. Kuo, J.H. Strickler, J.C. Krauss, B.T. Li, C.S. Denlinger, G. Durm, J. Ngang, H. Henary, G. Ngarmchamnanrith, E. Rasmussen, P.K. Morrow, D.S. Hong
Journal: Journal of Thoracic Oncology (2019)
Characterization of Monoclonal Gammopathy of Undetermined Significance Progression to Multiple Myeloma through Meta-Analysis of GEO Data
Authors: Jihad Aljabban, David Chen, Francesca Cottini, Saad Syed, Nabeal Aljabban, Sharjeel Syed, Tiffany Hughes, David Feldman, Dexter Hadley, Don M. Benson
Journal: Blood (2019)
Potential Anti-Thrombotic Effect without Accompanying Hemorrhage with Fostamatinib Use in Patients with Immune Thrombocytopenia
Authors: Ivy Altomare, Vadim V. Markovtsov, Leslie Todd, Dheepika Weerasinghe, Robert P. Numerof, Sandy Tong, Esteban Masuda, James B. Bussel
Journal: Blood (2019)
Sustained Hematopoietic Recovery after Salvage Autologous Stem Cell Transplants after Long Term Storage of Cryopreserved Hematopoietic Progenitor Stem Cells (HPSC)
Authors: Sarah S. Makhani, Ronit Reich-Slotky, Pashna N. Munshi, Noa Biran, Michele L. Donato, Stuart L. Goldberg, Andrew L. Pecora, David S. Siegel, David H. Vesole, Scott D. Rowley
Journal: Blood (2019)
Breakthroughs in Preclinical Development of Ataluren (PTC124) As Therapeutic Option for Patients Affected By Shwachman-Diamond Syndrome: Towards the First Clinical Trial
Authors: Valentino Bezzerri, Antonio Vella, Elisabetta D'Aversa, Martina Api, Marisole Allegri, Elena Marinelli Busilacchi, Giovanna D'Amico, Roberto Gambari, Claudio Sorio, Benedetta Fabrizzi, Vincenzo Bronte, Antonella Poloni, Monica Borgatti, Marco Cipolli
Journal: Blood (2019)
Challenging the Association of Marijuana Laws With Teen Marijuana Use
Authors: Christopher M. Jones, J. Michael Underwood, Nora D. Volkow
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
TMOD-33. AN INTEGRATED APPROACH COMBINING MATHEMATICAL AND GENOMIC METHODS TO REVEAL THE OPTIMAL TIMING OF THERAPEUTIC INTERVENTION IN WHO GRADE II DIFFUSE GLIOMA
Authors: Kosuke Aoki, Takashi Yamamoto, Hiromichi Suzuki, Sachi Maeda, Melissa Ranjit, Kazuya Motomura, Hideo Nakamura, Yoshitaka Narita, Mitsutoshi Nakada, Shoichi Deguchi, Masahiro Mizoguchi, Yasutomo Momii, Yoshihiro Muragaki, Tatsuya Abe, Jiro Akimoto, Toshihiko Wakabayashi, Hiroshi Haeno, Atsushi Natsume
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND In WHO grade II diffuse gliomas (low-grade gliomas, hereafter called LGGs), chemotherapy and radiotherapy contribute to prolonged survival but could induce somatic mutations. The optimal timing of treatment in LGGs remain poorly understood. To delineate this, we designed a mathematical model for tumor growth and investigate the association among the treatment, malignant transformation (MT), and the accumulation of somatic mutations revealed by whole exome sequencing (WES) in LGGs. METHODS Totally, 290 patients with LGGs between 1990 and 2018 were analyzed. We assessed the statuses of IDH mutation and 1p19q co-deletion in all tumors. Among all, 114 patients (39%) underwent MT during follow-up periods (mean: 82.6 months). Tumor volume was evaluated with FLAIR and/or T2-weighted MRI. MT was evaluated with contrast-enhanced MRI and/or pathological diagnosis. To investigate the number of somatic mutations in a cohort of LGGs and their patient matched recurrence, WES was performed on 88 serial samples collected at least two time-points from 39 patients. RESULTS Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (OD) showed longer transformation-free survival compared to other subtypes. An exponential model was chosen to estimate growth rate in LGGs, since the exponential model provided a better fit to our data as compared to a linear model. The growth rate significantly decreased in the middle of chemotherapy and after radiotherapy. By contrast, these treatments increased the number of somatic mutations identified by WES and the rate of MT in each subtype. The increasing number of mutations in recurrent tumors showed strong correlation with the rise in MT rate. Based on the growth rate and the risk of MT, optimal timing of treatments could be calculated for each genetic subtype. CONCLUSIONS The mathematical model and WES analysis delineates the optimal timing of treatments in each subtype, which will help to decide the treatment for LGGs.
Abstract 13091: Prevalence and Sociodemographic Variation in Non-Cigarette Tobacco Products Use Among Never Cigarette Smokers Adults in the United States
Authors: Javier Valero Elizondo, S M Uddin, Aruni Bhatnagar, Andrew P DeFilippis, Wasim Maziak, Michael J Blaha, Khurram Nasir
Journal: Circulation (2019)

Background: Cigarette consumption has been slowly declining, but the use of non-cigarette tobacco products is on the rise. With the spread of poly-tobacco use, identifying the characteristics of ot...
RARE-24. GROWTH PATTERN ANALYSES OF HEMANGIOBLASTOMA IN SPORADIC AND VHL CASES
Authors: Hirokazu Takami, Terry Burns, Ian Parney
Journal: Neuro-Oncology (2019)

Abstract Central nervous system hemangioblastoma (CNS HGB) is a rare neoplasm. Sporadic and von-Hippel Lindau (VHL)-associated forms exist. Predicting tumor growth is difficult, making the indication for intervention challenging. A retrospective analysis of consecutive, neurosurgically managed CNS HGB at Mayo Clinic spanning 1988–2018 was performed to clarify their characteristics. 117 sporadic and 67 VHL HGBs were reviewed. 9 sporadic lesions (8 cases) and 80 VHL lesions (35 cases) had tumor size data at ≥4 follow-up time-points beyond 1 year. The median follow-up was 8.0 years. No statistical difference existed between sporadic and VHL lesions regarding growth speed or growth latency (period of time without growth). Symptomatic lesions showed faster growth than asymptomatic lesions (2.79 vs 0.59 cm3/month, p=0.005). Solid and cystic portions often showed different growth patterns in cases harboring both (66.7%). Cyst growth was faster than solid portions (1.22 vs 1.05cm3/month, p=0.009) and growth latency was longer in the latter (15.2 vs 18.5%, p=0.25). Lesions’ growth were classified as linear (7), exponential (49), cubic (regressed to cubic function curve, 7), saltatory (19) and no-growth (7) patterns. Growth latency often existed in growing lesions (27-out-of-64 linear/exponential/cubic lesions, 57.8%), being average 8.3% of follow-up time. Contrarily, although saltatory lesions grew slower than exponential lesions (p=0.03), their overall growth speed was comparable to linear/cubic lesions (0.67cm3/month), and 9-out-of-19 showed growth surges at their ends. Growth speed at each follow-up roughly depended on the tumor size in cubic regression (R2=0.52). However, whereas total 18/821 time-point lesions showed rapid growth (≥1cm3/m, 2.2%), relatively small lesions (≤2cm3) also occasionally showed rapid growth (5/687, 0.73%). Not all large (&gt;5cm3) lesions grew rapidly (8/62, 12.9%). These results revealed while symptomatic/large/cystic lesions tend to grow more rapidly, HGB behavior is difficult to predict, which stresses the importance of careful follow-up.
Impact of Sickle Cell Disease Symptoms on Patients' Daily Lives: Interim Results from the International Sickle Cell World Assessment Survey (SWAY)
Authors: Ifeyinwa (ify) Osunkwo, Biree Andemariam, Baba PD Inusa, Fuad El-Rassi, Beverly Francis-Gibson, Alecia C. Nero, Caterina P. Minniti, Cassandra Trimnell, Miguel R. Abboud, Jean-Benoît Arlet, Raffaella Colombatti, Mariane de Montalembert, Suman Jain, Wasil Jastaniah, Erfan Nur, Laurie DeBonnett, John James
Journal: Blood (2019)
GENE-40. CHARACTERIZING EPIGENETIC INTRATUMORAL HETEROGENEITY IN GLIOMA USING SINGLE-CELL BISULFITE SEQUENCING
Authors: Kevin C Johnson, Kevin Anderson, Elise Courtois, Floris Barthel, Michael Samuels, Paul Robson, Ketan Bulsara, Sunit Das, Roel Verhaak
Journal: Neuro-Oncology (2019)

Abstract Genetic and epigenetic alterations contribute to the observed intratumoral heterogeneity in adult glioma. Current glioma classification, based on genotype (e.g., IDH1 mutations) and DNA methylation profiles (e.g., glioma CpG Island Methylator Phenotype), can provide clinically relevant tumor subgroups. However, traditional bulk sampling fails to adequately capture the full complement of epigenomic heterogeneity, and may mask deadly features present in less abundant glioma cells. To more precisely characterize the glioma epigenome, we separately profiled single-cell DNA methylation (Reduced Representation Bisulfite Sequencing, RRBS), single-cell RNA expression (10X genomics), and bulk whole genome sequencing in nine gliomas. The genomic regions profiled by scRRBS were primarily gene promoters, but adequate coverage was also reached for glioma-specific enhancer elements and binding sites of chromatin remodelers. Unsupervised clustering of single-cell DNA methylation data revealed intratumoral variability in epigenetic classification and these cell types were distinguished by regulatory element DNA methylation. We further integrated single-cell epigenetic, single-cell transcriptomic, and genomic features to better understand gene regulation and reconstruct each tumor’s lineage history. Together, our study aims to generate a glioma cellular hierarchy shaped by the epigenetic programs that drive tumor growth.
CBMT-09. THERAPEUTIC EFFECT OF INDUCTION OF POLYGLUTAMYLATION IN HIGH-DOSE METHOTREXATE THERAPY TO PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Kenji Fujimoto, Naoki Shinojima, Keishi Makino, Koichi Ichimura, Akitake Mukasa
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. Methotrexate (MTX) incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. In this study, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status and evaluated the combined effect of MTX and the drugs which upregulated polyglutamylation of MTX. METHODS Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma cell lines were used for in vitro and in vivo experiments. The association of polyglutamylation and the response to MTX with LV rescue was assessed in these cell lines. Histone-deacetylase inhibitor (HDACI) has been reported to induce polyglutamylation by elevating folpolyglutamate synthetase (FPGS) expression, so the effects of HDACIs on polyglutamylation were evaluated. Combined effects of MTX and HDACI were evaluated by cell viability assay and xenograft mouse models. RESULTS The complete response rate was significantly higher in the group with polyglutamylation than in the non-polyglutamylation group [58.1% (25/43) and 33.3% (13/39), respectively] (p &lt; 0.05), and progression-free survival was also significantly increased in the group with polyglutamylation (p &lt; 0.01). The combined effect of MTX and HDACI was significantly enhanced in cell viability assay in vitro (p&lt; 0.05), in subcutaneous (p&lt; 0.001) and intracranial tumor xenografts (p&lt; 0.001). CONCLUSION These findings suggested that polyglutamylation could be a predictor of therapeutic response to HD-MTX therapy with LV rescue in PCNSL. Combined therapy with HD-MTX and HDACIs might represent a promising treatment for HD-MTX resistant intractable PCNSL.
CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES
Authors: T Jonathan Yang, Suzanne Wolden, Josh Yamada, Michelle Mehallow, Anna Skakodub, Robert Young, Igor Gavrilovic, Andrew Lin, Bianca Santomasso, Christian Grommes, Anna Piotrowski, Lauren Schaff, Jacqueline Stone, Adrienne Boire, Elena Pentsova
Journal: Neuro-Oncology (2019)

Abstract Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiation (CSI) in contrast treats the entire central nervous system (CNS) compartment thus potentially improves disease control. We performed a phase IB study of proton CSI using 30CGE in 10 fractions for treating solid tumor LM (NCT03520504). The primary end point is dose-liming toxicity (DLT) within 1 month of treatment. Clinical outcomes and CSF circulating tumor cells (CTCs) by CellSearch® were evaluated. Overall (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Of the 24 patients enrolled, 4 were excluded from analysis: 3 did not complete treatment due to CNS or systemic disease progression (PD), and 1 completed treatment outside study window. The majority of patients had metastatic lung (55%) and breast (30%) malignancies. At this submission, the median follow-up was 2.8 months (0.5–9.4 months). No DLT was observed. Treatment-related grade 2+ toxicities were: fatigue (G2=43%), anorexia (G2=5%), anemia (G2=10%), thrombocytopenia (G3=5%, G2=10%), and leukopenia (G3=14%, G2=14%). Median survival is not reached with 17 patients (85%) alive with stable/improved LM including 2 with durable CNS control for &gt;9 months, 1 patient alive with CNS and systemic PD at 3.7 months, 2 patients died at 3.6 and 5.1 months with CNS and systemic PD. At 3-month, OS and PFS were 100% and 90% (95% CI 100–72%), respectively. In the 13 patients with CSF CTCs evaluation, decreased quantifiable CTCs at 1-month after proton CSI correlated significantly with improved CNS PFS (log-rank p=0.014). These early findings suggest that proton CSI is a safe and potentially effective treatment for patients with solid tumor LM. CSF biomarkers assessment is needed to better elucidate predictors of response.
ESR in gonococcal arthritis.
Authors: R K Tan, D G Miller
Journal: BMJ (1979)

treatment with prazosin, or prazosin plus a beta-blocker.Pape et all report similar findings in 14 patients, of whom 13 had negative ANF tests before and after prazosin and one a positive pretreatment test, which became negative after 18 weeks on prazosin.Marshall points out that his ANF findings are unlike those of systemic lupus erythematosus and that no patient had symptoms of an autoimmune illness.This is in agreement with my experience in 85 patients now treated with prazosin for periods up to five years (total patient years 255).There have never been signs or symptoms indicating an autoimmune reaction, nor have any significant laboratory abnormalities been found.
GENE-43. TARGETING GABPb1L INHIBITS IN VIVO GROWTH OF TERT PROMOTER MUTANT GLIOBLASTOMA
Authors: Alexandra Amen, Rachel Lew, Shawn Ren, Andrew McKinney, Andrew Mancini, Jennifer Doudna, Christof Fellmann, Joseph Costello
Journal: Neuro-Oncology (2019)

Abstract Understanding cancer cell immortality in primary glioblastoma (GBM) is essential for the development of more informed treatments. Multiple cancer types, including &gt;80% of GBMs, undergo immortalization by reactivating Telomerase Reverse Transcriptase (TERT) through acquired mutations in the TERT promoter. TERT, the catalytically active and rate-limiting subunit of telomerase, functions to maintain telomeres, which cap and protect the ends of chromosomes. Our past work has demonstrated that the transcription factor GABP - and specifically its tetramer-forming isoform GABPb1L - binds and activates the mutant TERT promoter. The generation of CRISPR-induced indels in GABPb1L results in a gradual loss of cell viability in TERT promoter mutant but not TERT promoter wild type tumor cells in vitro, but the extent to which GABPb1L function is compromised in this setting is unclear. Thus, the potential for use of GABPb1L as an effective therapeutic target for TERT promoter mutant GBM requires further investigation. Here, we use CRISPR-based strategies to demonstrate that full knockout of GABPb1L is rapidly lethal in TERT promoter mutant cells in vitro, in association with a decrease in both TERT mRNA and telomerase activity. Heterozygous deletion of GABPb1L in the context of TERT promoter mutations leads to slowed growth of orthotopic xenograft tumors in mice, and prolonged survival. Additionally, inducible RNAi-mediated inhibition of GABPb1L in growing tumors is also capable of decreasing tumor burden and increasing survival, further strongly suggesting that targeting GABPb1L in patient tumors could be a viable treatment strategy. Finally, reduced GABPb1L synergizes with temozolomide (TMZ) therapy such that TMZ treatment in the context of low GABPb1L and low TERT leads to a complete ablation of orthotopic GBM xenografts. These results highlight the potential to improve disease outcomes by targeting TERT through inhibition of GABPb1L, particularly in conjunction with TMZ treatment.