tbuckley/cabot-search huggingface dataset:
METB-01. NANOPARTICLE-BASED MAGNETIC RESONANCE IMAGING (MRI) AND METABOLOMICS OF RADIATION AND TMZ INDUCED INFLAMMATION IN GLIOMA MODELS
Authors: Paul Hong, Heather Caulkins, Natalie Serkova
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) is the most common primary malignancy in adults, and one that nearly always recurs. Maximal surgical resection followed by radiotherapy (RT) and concurrent chemotherapy with temozolomide (TMZ) is the current standard of care treatment. It often causes a macrophage-driven inflammation called pseudoprogression (PsP) which appears as abnormal MRI enhancement mimicking treatment response. The purpose of this study was to use quantitative T2-weighted MRI (qT2MRI) after injection of iron-oxide nanoparticles (Ferumoxytol) to mitigate this diagnostic challenge, and to correlate to the in vitro findings. In vitro murine GL261 and human U251 glioblastoma cell lines were cultured and treated with TMZ or RT, and quantitative 1H-nuclear magnetic resonance (NMR) metabolomics was performed to evaluate the metabolic changes. Metabolomics revealed decreased lactate production after both RT or TMZ, and glucose uptake decreased with RT only. A significant decrease in amino acid uptake and metabolism (glutamine, glycine, methionine, and tyrosine) were observed after TMZ, while RT led to a significant shut down of membrane phospholipid synthesis. In vivo studies involved injecting 10 million U251 and GL261 cells into the R flanks of the female nude athymic (xenograft) and wild-type mice (isograft). When the tumors reached sizes of 250-300 mm3, mice were treated on either oral TMZ for 5 days, or 10 Gy RT. Tumors were then scanned with qT2MRI, followed by injection of 30 mg/kg Ferumoxytol. The SPIONS are taken up uniquely by inflammatory macrophages, as shown by decreased T2-relaxation times observed for both treatments. When compared with tissue flow cytometry assay, percentage increase in the F4/80 macrophage markers were consistent with the MRI results (10% untreated, 29% treatment). These newly discovered imaging and metabolic signatures may provide a promising discernment of PsP (nanoparticle-based qT2MRI) and true progression (glucose, amino acid and phospholipid metabolomics) during the treatment of glioblastoma.
Épidémie d’infections à Salmonella enterica sous-espèce Enterica sérotype Enteridis (Salmonella Enteridis) dans un hôtel au Royaume-Uni, 2006
Authors: N Calvert, L Murphy, A Smith, D Copeland, M Knowles
Journal: Eurosurveillance (2007)

Une epidemie de salmonellose a Salmonella Enteridis lysotype PT4 d’origine alimentaire a eu lieu en Cumbria, au nord-ouest de l’Angleterre, durant l’ete 2006. Quinze personnes, dont les echantillons de selles etaient positifs, correspondaient a la definition du cas ; trois d’entre elles ont ete hospitalisees, et l’une de ces trois personnes est decedee.
ACTR-44. AUTOPSY STUDY ON THE EFFECTS OF TUMOR TREATMENT FIELDS IN RECURRENT GLIOBLASTOMA: PRELIMINARY RESULTS AND TRIAL DESIGN
Authors: Sarah Hurrell, Elizabeth Cochran, Sean McGarry, Jennifer M Connelly, Kathleen M Schmainda, Scott Rand, Wade M Mueller, Peter LaViolette
Journal: Neuro-Oncology (2017)

Optune therapy with tumor treatment fields (TTFields) is approved for the treatment of recurrent glioblastoma due to a recent clinical trial that showed better quality of life and comparable overall survival to conventional therapy. In the newly diagnosed setting, the addition of TTFields to standard therapy consisting of surgery, radiation and temozolomide has also been shown to prolong tumor progression and improve overall survival. TTFields are low-intensity, alternating frequency electric fields that have been shown to disrupt cell division and subsequently tumor growth. Apoptosis and cell cycle arrest have been seen in vitro, and shown in mice and rabbit tumor models. Though preclinical studies are ongoing, glioblastoma patients who have undergone TTFields therapy have not yet been assessed at autopsy to determine both the pathological signature of TTFields therapy, and the pattern of failure. Whole brain samples were acquired and analyzed pathologically from two recurrent GBM patients at autopsy. One patient served as a control and one considered a test patient who had undergone TTFields therapy. Tissue samples were acquired from regions suspicious of tumor and treatment effects. Samples were paraffin embedded and hematoxylin and eosin (H&E) stained, and pathologically reviewed by a board certified pathologist. Samples were then compared. The patient who underwent TTFields therapy showed regions of necrosis and increased cellular debris compared to the control patient who had pseudo-palisading and radiation necrosis. These findings suggest there is increased apoptosis in patients treated with TTFields compared to those on chemoradiation alone. Recruitment is ongoing for expansion of this study to include 10 patients treated with TTFields at recurrence and 10 at treated at initial diagnosis. Patients will be recruited from brain donation. Pathology will be compared to control patients naïve of TTFields therapy.
MBRS-06. Gli3 INDUCES NEURONAL DIFFERENTIATION IN WNT- AND SHH- ACTIVATED MEDULLOBLASTOMA
Authors: Manabu Natsumeda, Hiroaki Miyahara, Junichi Yoshimura, Yoshihiro Tsukamoto, Makoto Oishi, Takafumi Wataya, Charles Eberhart, Akiyoshi Kakita, Yukihiko Fujii
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND We have previously investigated the expression of Gli3, a downstream target of the Sonic Hedgehog pathway, which main function is to suppress Gli1/2 in medulloblastomas. We found that Gli3 is associated with neuronal and glial differentiation in desmoplastic / nodular (D/N) type medulloblastomas (Miyahara et al., Neuropathology, 2013). In the present study, we investigated the expression of Gli3 in molecular subgroups. METHOD Thirty-one medulloblastomas treated at Niigata University between 1982 and 2013 were studied. Molecular classification into 4 subgroups (WNT-activated, SHH-activated, Group 3 and Group 4) using Nanostring and immunohistochemistry was performed. Furthermore, Gli3 and Gli1 expression in molecular subgroups was assessed using public data bases. RESULTS Nanostring was considered reliable (confidence &amp;gt; 0.9) in 28 cases. Four cases were classified as WNT-, 5 cases as SHH-activated, 4 cases as Group 3 and 16 cases as Group 4. Gli3 was positive in 7 out of 9 (78%) WNT-/SHH- cases, but positive in only 8 out of 19 (42.1%) non-WNT-/SHH- subgroup cases (p = 0.1145, Fisher’s exact test). R2 database analysis confirmed that Gli3 was significantly elevated in WNT- and SHH-activated medulloblastoma. Gli1 was elevated in SHH-activated cases but suppressed in WNT-activated cases. IHC analysis revealed that Gli3 was elevated inside nodules showing neuronal differentiation in D/N type medulloblastoma. Results of single cell RNA analyses were consistent with those of IHC, Nanostring and R2. CONCLUSION These results suggest that Gli3 is elevated inside the nodules of SHH-activated medulloblastoma, whereas in WNT-activated cases, Gli3 diffusely suppresses HH signaling.
Germline variants and clinical outcomes of high-risk stage II and stage III colon cancer patients treated with oxaliplatin and fluoropyrimidines adjuvant chemotherapy: a pharmacogenetic ancillary study to TOSCA trial
Authors: A. Ruzzo, F. Galli, F. Galli, E. Rulli, S. Lonardi, V. Zagonel, M. Ronzoni, M.T. Ionta, N. Pella, C. Mucciarini, R. Labianca, E. Veltri, P. Sozzi, S. Barni, M. Nicolini, E. Biondi, A. Bramati, D. Turci, M. Buscaglia, M. Magnani, F. Graziano
Journal: Annals of Oncology (2017)
Should venous ammonia be used in decision‐making acute liver failure patients?
Authors: Chetan Kalal, Akash Shukla, Ravi Mohanka, Samir Shah
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We congratulate Cardoso et al.1 on their study published in a recent issue of Hepatology that analyzed the effect of continuous renal replacement therapy (CRRT) on serum ammonia levels and mortality in acute liver failure (ALF). The researchers have concluded that CRRT may be an effective adjunctive therapy to improve hyperammonemia as well as transplant‐free survival. In the study, the researchers have used either arterial (n = 509) or venous (n = 677) ammonia on admission for analysis. The rationale for the same was based on the study by Ong et al., who had shown venous sampling to be adequate for ammonia measurement.2 Unlike Cardoso et al.'s study, that study was conducted in patients with cirrhosis with or without overt hepatic encephalopathy (HE). Arterial ammonia levels are more reliable than venous ammonia, given that they later may be affected by peripheral metabolism and its uptake by muscle and brain tissue.3 Arterial and venous differences of ammonia is considerable in ALF (160 ± 53 vs. 110 ± 35 μg/dL in the femoral vein; P < 0.05).4 Similarly, it is now known that, whereas arterial ammonia levels correlate well with severity of HE, venous ammonia does not correlate with arterial ammonia or severity of HE.5 Therefore, all recommendations in ALF suggest use of arterial ammonia alone. Arterial ammonia on admission is also predictive of complications and survival in patients with ALF and can be used for risk stratification. Ammonia values from ≥124 μmol/L are associated with poor outcomes and constitute an indication for initiating CRRT in various patient populations, and a similar strategy would have been useful in the present study, too. It would have been more meaningful if arterial and venous levels were analyzed and correlated separately in the present study. With current evidence, we feel that venous ammonia should not be considered while deciding treatment strategies for patients with ALF.
Hypertonic Saline and Acute Bronchiolitis—Reply
Authors: François Angoulvant, Karen Milcent, Vincent Gajdos
Journal: JAMA Pediatrics (2017)

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
P3.16-003 The Clinical Significance of Immune-Nutritional Parameters in Surgically Resected Elderly Patients with Non-Small Cell Lung Cancer
Authors: F. Shoji, N. Miura, T. Akamine, T. Matsubara, Y. Kozuma, N. Haratake, S. Takamori, M. Katsura, K. Takada, G. Toyokawa, T. Takenaka, K. Yamazaki, T. Okamoto, S. Takeo, Y. Maehara
Journal: Journal of Thoracic Oncology (2017)
IMMU-60. PD-L1 EXPRESSION ASSOCIATED WITH GLIOMA MOLECULAR SUBTYPES: CLINICAL IMPLICATIONS
Authors: Tathiane Malta, James Snyder, Steven Kalkanis, Ana Valéria Castro, Houtan Noushmehr
Journal: Neuro-Oncology (2017)

The development of immune checkpoint blockade therapy has ushered in a new era of cancer treatment. The use of inhibitors targeting programmed cell death protein 1 (PD1) and/or its ligand 1 (PD-L1) has shown activity in several cancer types and is currently being tested in glioma clinical trials. Previous reports suggested that therapeutic responses are more frequent in patients with higher expression of PD-L1; however, this has been disputed. We aim to evaluate PD-L1 expression in glioma samples and its association with clinical and molecular features. We used protein expression, RNA expression, and DNA methylation data from glioma samples profiled by TCGA (n=1,122). PD-L1 protein and CD274(PD-L1) gene expression were positively correlated (p<0.001). PD-L1 expression was upregulated in IDH-wildtype gliomas compared to IDH-mutant (p<0.001) and was associated with poor overall survival (HR=2.392, p<0.001). When PD-L1 was evaluated in the context of recently described TCGA glioma molecular subtypes, we found high PD-L1 expression in the mesenchymal-like and classic-like subtypes, which present poor outcome among all gliomas. Interestingly, PD-L1 protein expression is the lowest in the G-CIMP-low subgroup, which has a GBM-like molecular phenotype and overall poor outcome among IDH-mutants. In fact, within IDH-mutant cohort, PD-L1 expression did not correlate with clinical outcome. We found higher promoter methylation of PD-L1 in IDH-mutant tumors compared to IDH-wildtype. PD-L1 promoter methylation was negatively correlated with PD-L1 gene expression suggesting an epigenetic regulation of PD-L1. Our findings suggest that G-CIMP-low, which has low expression of PD-L1, might not benefit from PD1/PD-L1 blockade. Therefore, we suggest that glioma molecular subtypes should be considered in PD-L1 blockade clinical trial design. Moreover, since PD-L1 expression seems to be regulated by promoter methylation, adding demethylating agents to immunotherapy may improve therapeutic outcomes in gliomas. Further exploration into the mechanisms of tumor immunity and its epigenetic regulation is warranted.
Recomendaciones europeas en materia de vigilancia de resistencias a fármacos antituberculosos
Authors: V Schwoebel, C S B Lambregts, M. L. Moro, F Drobniewski, S. E. Hoffner, M. C. Raviglione, H. L. Rieder
Journal: Eurosurveillance (2000)

La resistencia a farmacos antituberculosos, cuyo alcance en Europa esta deficientemente documentado, es una grave amenaza para el control de la tuberculosis. El objetivo de las ultimas recomendaciones europeas en materia de vigilancia de la resistencia a farmacos antituberculosos, publicadas por un grupo de trabajo compuesto por representantes de la OMS, la IUATLD y 35 paises de la Region Europea de la OMS, es mejorar la estandarizacion de las definiciones y los metodos. Estas recomendaciones hacen hincapie en el aseguramiento de la calidad y en posibilitar una union entre los datos de laboratorio y los datos de las notificaciones clinicas. La vigilancia de la resistencia a farmacos antituberculosos debe formar parte de la vigilancia de la tuberculosis.
Molecular profile characterization and impact on clinical outcome in metastatic NSCLC patients enrolled in MOSCATO 01 trial
Authors: G. Buzzatti, A. Allorant, L. Verlingue, D. Brandao, C. Massard, A. Hollebecque, C. Ferté, L. Lacroix, M. Ngo-Camus, N. Auger, J. Scoazec, S. Ammari, A. Gazzah, D. Planchard, B. Besse, E. Solary, F. André, S. Michiels, J. Soria, J. Menis
Journal: Annals of Oncology (2017)
Une stratégie pour améliorer et évaluer la couverture vaccinale dans le nord du Portugal
Authors: G Gonçalves, M A Frutuoso, M C Ferreira, M G Freitas
Journal: Eurosurveillance (2005)

Dans la region sanitaire du nord du Portugal, la couverture vaccinale a ete mesuree a partir des registres (verifies prealablement) de vaccination individuels des centres de soins. Chaque annee entre 2001 et 2004, des cohortes par dates de naissance (enfants de plus de 2, 6 et 14 ans) ont ete selecionnees pour l’evaluation. Les donnees etaient recueillies en janvier de l’annee suivante, puis chaque mois de mars des reunions etaient organisees avec les coordinateurs de vaccination par district. Les couvertures vaccinales observees dans le nord du Portugal etaient excellentes, pour tous les vaccins et cohortes de naissance pris en compte. L’article suivant compare avec les donnees de la litterature internationale sur la couverture vaccinale, et discute sur la validite des resultats. Il en ressort que nos donnees de couvertures vaccinales ne semblent pas entachees de biais importants, meme si la prudence est de rigueur lors de comparaisons avec des donnees internationales ; les methodes que nous avons utilisees ont contribue a ameliorer la couverture vaccinale.
Perplexing Conclusions Concerning Heat-Not-Burn Tobacco Cigarettes—Reply
Authors: Reto Auer, Jacques Cornuz, Aurélie Berthet
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Abstract 15976: A New Electrocardiographic Marker for Recurrence of Atrial Fibrillation After Electrical Cardioversion
Authors: Yuhi Fujimoto, Kenji Yodogawa, Kenta Takahashi, Ippei Tsuboi, Teppei Yamamoto, Yu-ki Iwasaki, Meiso Hayashi, Wataru Shimizu
Journal: Circulation (2016)

Backgrouds:  Early recurrence of atrial fibrillation (AF) is common following successful electrical cardioversion (ECV). We hypothesized that recurrence of AF is related to impaired electrical conduction of Buchman’s Bundle, which may potentially be attributed to biphasic P wave morphology in III, aVf leads.   Methods:  Consecutive 178 persistent AF patients who were to undergo ECV were enrolled, and evaluated for recurrence of AF after 1 month after ECV. Patients with open-heart surgery, history of catheter ablation, and an unsuccessful ECV were excluded. P wave duration and dispersion, and P wave morphology were evaluated by 12-lead ECG immediately after ECV. The parameters of transthoracic echocardiography were also evaluated before ECV.   Results:  After exclusion criteria were applied, 88 patients were investigated. One month after ECV, 40 (45%) patients maintained sinus rhythm. Compared with the non-recurrence group, those with recurrent AF had significantly greater number of the patients with biphasic P wave morphology in both III, aVF leads (27% vs 10% P= 0.04, sensitivity 30%, specifity 92%), greater P wave dispersion (54 ± 17 vs 46 ± 12 ms, P= 0.02), and longer undergoing AF periods (40 ± 45 vs 20 ± 18 months, P= 0.006). Biphasic P wave morphology in both III, aVF leads were not associated with structural parameters such as left atrial diameter, left atrial area.   Conclusions:  The risk of AF recurrence after ECV can be predicted by biphasic P wave morphology in III, aVF leads.
TMIC-44. RNA-MODIFIED T CELL AS A PLATFORM TO DELIVER IMMUNOMODULATORY AGENTS TO BRAIN TUMOR
Authors: Fernanda Guimaraes
Journal: Neuro-Oncology (2017)

Cancer immunotherapy using immunomodulatory agents can potentially meet clear and urgent need for effective therapeutics for invasive malignant brain tumors. Cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF) have been applied as an adjuvant in cancer immunotherapy in attempt to potentiate anti-tumor immunity and overcome the robust immunosuppressive tumor microenvironment. Although this approach has proven efficacy, systemically delivered immunomodulatory agents to brain tumors have limited access to the central nervous system (CNS) due to the blood brain barrier (BBB). Furthermore, it may require high dose regimens to reach therapeutic concentrations at the tumor site, increasing the risk of systemic side effects and induction of potentially counterproductive immune responses. To overcome these limitations, we investigate the HYPOTHESIS that RNA-modified T cells can deliver immunomodulatory molecules directly to brain tumor microenvironment. The ability of T cells to cross the BBB and specifically lyse tumor cells make them an attractive tool for cancer cell therapy. Using mRNA electroporation (EP) approach, we evaluated GM-CSF secretion in vitro and in vivo following intravenous injection of GM-CSF RNA-modified T cells. In addition, we further tested anti-tumor efficacy of GM-CSF RNA modified T cells in a murine brain tumor model. Murine and human activated T cells can be modified to secrete GM-CSF protein in vitro, while retaining effector T cell functions. Moreover, our results demonstrated the capacity for GM-CSF RNA-modified T cell to deliver enhanced cytokine concentrations to intracranial tumors in vivo. Finally, we demonstrated that GM-CSF RNA-modified T cell potentiated antigen-specific T cell expansion and prolonged overall survival in a murine brain tumor model. Our findings suggest that activated RNA-modified T cells cross the BBB, and can be used as an effective cellular vehicle to deliver therapeutic molecules effectively to invasive brain tumors.
P2.02-059 Genomic Mutation Patterns Detected with Cancer Panel Can Predict Postoperative Prognosis in Clinical Stage I Adenocarcinoma
Authors: K. Hyun, Y.J. Jung, S. Im, Y.H. Kim, S.B. Lee, S. Park, H.J. Lee, I.K. Park, C.H. Kang, Y. Kim
Journal: Journal of Thoracic Oncology (2017)
PDTM-32. PF-A EPENDYMOMAS SHOW TYPICAL PLASTIC EPENDYMOMAS
Authors: Akira Gomi
Journal: Neuro-Oncology (2017)

The molecular classification of ependymoma has recently progressed. Ependymomas occurring in the posterior fossa are classified into subtypes PF-A and PF-B. PF-A ependymomas show clinical characteristics of a predilection for younger patients (including infants), lateral extension, a tendency to disseminate, and poor prognosis. Here we discuss tips for surgery according to pathological findings from PF-A ependymomas. We retrospectively evaluated the surgical and pathological findings for pediatric patients with ependymoma treated in our institute from 2001 to 2015. We examined cases of PF-A ependymoma occurring in the posterior fossa and progressing laterally to the cerebellopontine angle. Confirmation of the molecular diagnosis is ongoing. Two cases of PF-A ependymoma were evaluated. Surgical findings revealed that the tumors occurred at the foramen of Luschka, and progressed medially into the fourth ventricle and laterally to the cerebellopontine angle. The tumors engulfed the local cranial nerves and vertebrobasilar artery, but did not invade and were easily separated out. Pathological findings showed that the forward parts of the tumors were polypoid and comprised four layers: a superficial layer of linear cuboidal epithelium, resulting in a clear boundary; a GFAP-positive layer; an AE1/AE3-positive layer; and the innermost tissue of anaplastic ependymoma. The macroscopic features in our cases were similar to those described as “plastic ependymoma” in the World Health Organization classification. We conclude that the “plastic” feature is a special characteristic of PF-A ependymoma that needs to be considered when dissecting the tumor from adjacent nerves and arteries.