tbuckley/cabot-search huggingface dataset:
P14.65 Anaplastic pleomorphic xanthoastrocytoma: literature review& case report
Authors: G Agabekyan, G Kobyakov, K Lodygina, N Kobyakov, O Absalyamova, M Ryzhova, M Inozemcevа, A Poddubsky
Journal: Neuro-Oncology (2019)

Abstract Pleomorphic xanthoastrocytoma (PXA) is a rare glial brain tumor. 9% to 30% cases have anaplastic features which determine poor prognosis. Anaplastic features may be found either in primary tumor or in recurrent PXA in any time frame. According to WHO 2016 Brain Tumor Classification, anaplastic pleomorphic xanthoastrocytoma (aPXA) was reclassified as grade III tumor (previously grade II). Characteristic features for aPXA are mitotic index of 5% or higher and worse 5-year survival rates in comparison with PXA: 57.1% and 90.4%, respectively. About 6% cases have TP53 gene mutation. About 60–78% tumors are BRAF-mutated, which is a potential target for therapy. Currently there are ongoing clinical trials to determine efficacy of BRAF and MEK inhibitors in pediatric patients with high-grade glioma with BRAF mutation. There is a number of publications showing positive outcome of targeted therapy both in children and adults. Treatment protocol for aPXA has not been defined. Case report Patient N. 14-y.o. female. MRI showed tumor of left occipital lobe. 02.03.2016 stereotactic biopsy was performed. Histological examination revealed diffuse astrocytic glioma WHO grade III-IV. Radiation therapy was performed, after which patient’s condition abruptly deteriorated with back pain, patient became almost unable to walk, however control MRI showed no signs of spinal dissemination. 01.12.2016 surgery to remove left occipital lobe tumor was performed. 07.12.2016 MRI showed contrast enhancing lesions throughout entire length of the spinal cord. Histological examination revealed aPXA gr. III, Ki-67 up to 8%. From December to June 2017 patient received 6 cycles of chemotherapy with temozolomide. Molecular testing discovered BRAF V600 mutation in exon 15. Chemotherapy regimen was thereby changed to vemurafenib 1920 mg/day from July 2017. After a month of treatment patient developed cutaneous toxicity and the dose was lowered to 960 mg/day. Patient’s condition improved: back pain syndrome regressed, lower extremity muscle strength increased, patient became able to walk. MRI 03.12.2017 revealed an increase of contrast enhancing lesion and T2-FLAIR hyperintense signal area in left occipital lobe, no progression in spinal cord. Methionine PET/CT was performed, the findings were evaluated as a combination of radiation necrosis and glioma growth. In view of MRI and PET/CT findings, amount of time passed after radiation therapy, we decided to include bevacizumab 400 mg every 2 weeks in the regimen. Since January 2018 patient is receiving vemurafenib 960 mg/day and bevacizumab 400 mg every 2 weeks. There is a marked positive dynamic in clinical findings and imaging data (MRI and PET/CT). We report the patient with aPXA and prolonged response to targeted therapy. The presence of the BRAF V600E mutation was possibility of treatment which led to successful results.
Consensus on measurement of core dataset for AE treatment research registries
Authors: F.M. Vermeulen, L.A.A. Gerbens, A.L. Bosma, C.J. Apfelbacher, A.D. Irvine, B.W.M. Arents, S. Barbarot, M. Deleuran, L.F. Eichenfield, A. Manca, J. Schmitt, C. Vestergaard, D. Wall, S. Weidinger, M.A. Middelkamp‐Hup, P.I. Spuls, C. Flohr
Journal: British Journal of Dermatology (2019)

Moderate‐to‐severe atopic eczema (AE) is often treated with phototherapy (light treatment) or systemic therapy (medication that works throughout the whole body). Long‐term data on effectiveness and safety of these treatments is currently missing. To address this issue, data on paediatric and adult patients who use or used these treatments in a real‐life setting should be collected in national research registries. Ideally, these national registries should be compatible, so that data can be combined and analysed from as many patients as possible (which is needed to find rare side‐effects, for example). Therefore, every country needs to collect the same data in the same way. For this purpose the international TREatment of ATopic eczema (TREAT) Registry Taskforce has been established. It has already standardised which items need to be measured (e.g. disease severity, side effects). This study addresses the two remaining issues: how and when to measure these items. To determine how to measure the items (i.e. which measurement instruments to use), the authors used the recommendations from the Harmonising Outcome Measures for Eczema (HOME) initiative, relevant literature (published scientific studies), an already existing AE registry in Germany, and expert opinions. The proposals were discussed at multiple meetings and via email. This resulted in agreement (consensus) on how to measure the already standardised item‐set. The issue of when to measure the items, the follow‐up frequency, was resolved with an online survey. Consensus was reached on a minimum follow‐up frequency of 4 weeks after starting treatment, then every 3 months whilst on treatment and every 6 months whilst off treatment. A complete core dataset is now available that will help with the standardised collection of data of paediatric and adult AE patients on photo‐ and systemic therapies. This will help, in time, answer questions on the long‐term effectiveness and safety of these treatments and improve care for moderate‐to‐severe AE patients.
Clinical implications of routine testing for epidermal growth factor receptor (EGFR) mutations in patients with nonsquamous non-small cell lung cancer (NSCLC).
Authors: Hui Zhu, Andria Valeria Arrossi, Paul Elson, Carol Farver, Raymond R. Tubbs, Sudish C. Murthy, David P. Mason, Peter J. Mazzone, Nathan A. Pennell
Journal: Journal of Clinical Oncology (2013)

8113 Background: EGFR mutation (Mut) testing is recommended for all patients (pts) with advanced NSCLC to identify pts who may benefit from front-line EGFR tyrosine kinase inhibitor (TKI) therapy. In July 2010 the Cleveland Clinic initiated reflex EGFR testing of all new diagnoses of nonsquamous NSCLC, prior to which testing was done only by physician request. A retrospective study was designed to review how this change affected clinical practice in a large academic health center. Methods: All pts with NSCLC that had EGFR Mut testing performed at the Cleveland Clinic from 07/2009 to 02/2012 were included (n=287). Pt characteristics, tumor histology and stage, Mut status, treatments, and pt outcomes were collected from electronic medical records. Special attention was given to pts with EGFR Mut+ who received erlotinib (E). Data were analyzed using Fisher’s exact, chi-square and the Wilcoxon rank-sum tests. Results: See Table. Conclusions: Automatic EGFR mutation testing, recommended in an ASCO provisional clinical opinion in April 2011, was feasible in a large academic center and significantly shortened the time between diagnosis and EGFR status becoming available to guide treatment decisions. Although not statistically significant due to the small sample size, there were positive trends towards increased first line usage of E in pts with EGFR Mut+, better performance status, lower rates of E discontinuation due to toxicity, and higher response rate to E in the automatic testing group. There was no difference in overall survival between the two groups. [Table: see text]
Postoperative Recurrence of Hepatocellular Carcinoma: The Importance of Distinguishing between Intrahepatic Metastasis and Multicentric Occurrence—Letter
Authors: Yanjun Bai, Wenjie Liang
Journal: Clinical Cancer Research (2019)

We were quite interested in the recently published article by Kim and colleagues titled “Radiomics on gadoxetic acid–enhanced magnetic resonance imaging for prediction of postoperative early and late recurrence of single hepatocellular carcinoma” ([1][1]). Their MRI image–based radiomics
Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus
Authors: Hui Luo, Ling Wang, Ding Bao, Li Wang, Hongjun Zhao, Yun Lian, Mei Yan, Chandra Mohan, Quan-Zhen Li
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients’ blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (ProtoArray) was used to identify autoAbs that were significantly elevated in the sera of SLE patients. By comparing the autoAb profiles of SLE patients with those of healthy controls, we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE (P &amp;lt; 0.05). Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear, cytoplasmic, and membrane antigens. Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death, cell cycle, and DNA repair pathways. A group of autoAbs associated with cell apoptosis and DNA repair function, including those targeting APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S, and VRK1, were further validated by ELISA and Western blot in a larger cohort. In addition, the levels of autoAbs against APEX1, HMGB1, VRK1, AURKA, PADI4, and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients. Comprehensive autoAb screening has identified novel autoAbs, which may shed light on potential pathogenic pathways leading to lupus.
Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma
Authors: Allen S. Ho, Angelica Ochoa, Gowtham Jayakumaran, Ahmet Zehir, Cristina Valero Mayor, Justin Tepe, Vladimir Makarov, Martin G. Dalin, Jie He, Mark Bailey, Meagan Montesion, Jeffrey S. Ross, Vincent A. Miller, Lindsay Chan, Ian Ganly, Snjezana Dogan, Nora Katabi, Petros Tsipouras, Patrick Ha, Nishant Agrawal, David B. Solit, P. Andrew Futreal, Adel K. El Naggar, Jorge S. Reis-Filho, Britta Weigelt, Alan L. Ho, Nikolaus Schultz, Timothy A. Chan, Luc G.T. Morris
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Adenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed.
A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection
Authors: Jose Luis Slon-Campos, Wanwisa Dejnirattisai, Brett W. Jagger, César López-Camacho, Wiyada Wongwiwat, Lorellin A. Durnell, Emma S. Winkler, Rita E. Chen, Arturo Reyes-Sandoval, Felix A. Rey, Michael S. Diamond, Juthathip Mongkolsapaya, Gavin R. Screaton
Journal: Nature Immunology (2019)
Is the challenge for psychologists to return to behaviourism?
Authors: Denis J. Hilton
Journal: Behavioral and Brain Sciences (2001)

I suggest that contemporary economics shares many of the characteristics of methodological behaviourism in psychology, with its emphasis on the influence of motivation, learning, and situational incentives on behaviour, and minimal interest in the details of the cognitive processes that transform input (information) into output (behaviour). The emphasis on these characteristics has the same strengths and weaknesses in economics as in behaviourist psychology.
Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency
Authors: Rachael F. Grace, Christian Rose, D. Mark Layton, Frédéric Galactéros, Wilma Barcellini, D. Holmes Morton, Eduard J. van Beers, Hassan Yaish, Yaddanapudi Ravindranath, Kevin H.M. Kuo, Sujit Sheth, Janet L. Kwiatkowski, Ann J. Barbier, Susan Bodie, Bruce Silver, Lei Hua, Charles Kung, Peter Hawkins, Marie-Hélène Jouvin, Chris Bowden, Bertil Glader
Journal: New England Journal of Medicine (2019)

Pyruvate kinase deficiency is caused by mutations in PKLR and leads to congenital hemolytic anemia. Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase in red cells.In this uncontrolled, phase 2 study, we evaluated the safety and efficacy of mitapivat in 52 adults with pyruvate kinase deficiency who were not receiving red-cell transfusions. The patients were randomly assigned to receive either 50 mg or 300 mg of mitapivat twice daily for a 24-week core period; eligible patients could continue treatment in an ongoing extension phase.Common adverse events, including headache and insomnia, occurred at the time of drug initiation and were transient; 92% of the episodes of headache and 47% of the episodes of insomnia resolved within 7 days. The most common serious adverse events, hemolytic anemia and pharyngitis, each occurred in 2 patients (4%). A total of 26 patients (50%) had an increase of more than 1.0 g per deciliter in the hemoglobin level. Among these patients, the mean maximum increase was 3.4 g per deciliter (range, 1.1 to 5.8), and the median time until the first increase of more than 1.0 g per deciliter was 10 days (range, 7 to 187); 20 patients (77%) had an increase of more than 1.0 g per deciliter in the hemoglobin level at more than 50% of visits during the core study period, with improvement in markers of hemolysis. The response was sustained in all 19 patients remaining in the extension phase, with a median follow-up of 29 months (range, 22 to 35). Hemoglobin responses were observed only in patients who had at least one missense PKLR mutation and were associated with the red-cell pyruvate kinase protein level at baseline.The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase deficiency, with a sustained response during a median follow-up of 29 months during the extension phase. Adverse effects were mainly low-grade and transient. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02476916.).
Vegetarian and pescatarian diets are linked to lower risk of ischaemic heart disease, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Following a vegetarian (including vegan) or pescatarian diet is linked to a lower risk of developing ischaemic heart disease than eating a diet that includes meat, research has found.

But the prospective cohort study,1 carried out by University of Oxford researchers, also found that vegetarians and vegans had a higher risk of haemorrhagic and total stroke than meat eaters, which could be due to low blood levels of total cholesterol or a low intake of certain vitamins.

The researchers used data from the EPIC-Oxford study to explore the risks of ischaemic heart disease and stroke in meat eaters (participants who consumed meat, regardless of whether they also consumed fish, dairy, or eggs; n=24 428), pescatarians …
Real-time PM2·5 air pollution and social preferences: a large-scale behavioural game study using mobile apps in mainland China
Authors: Ying-yi Hong, King King Li, Bo Huang, Tony Tam
Journal: The Lancet Planetary Health (2019)

BackgroundAir pollution undermines people's physical health. So why wouldn't people take actions to reduce air pollution? We argue that social preferences might play a part. Specifically, we examined the links between air pollution, interpersonal trust, and preferences to buy so-called sin stocks (companies that polluted the environment). Because previous research has shown that high pollution induces a belief in immorality as a social norm (akin to "broken-window" effect), we predicted that pollution is linked to lower trusting and trustworthy behaviours, and higher likelihood to buy sin stocks. Second, we examined the moderating role of participants' subjective socioeconomic status (SSES). Specifically, previous studies have shown that low SSES induces a feeling of deprivation and higher vulnerability. Therefore, we predicted an interaction between pollution and SSES, such that low SSES participants in highly polluted environment should display the lowest levels of trusting and trustworthy behaviours, and highest likelihood to buy sin stock.MethodsWe recruited 4177 participants residing in 31 provinces of mainland China during January, 2018. Participants were asked to play three incentivised behavioural games measuring their likelihood to buy sin stocks, trusting behaviour, and trustworthiness, respectively. We disseminated our survey via a mobile phone application, making it possible to pay the participants according to their performance on the games, and estimate the instantaneous, real-time air pollution (PM2·5) from dynamic monitoring station data based on each participant's GPS information.FindingsWe found a robust main effect of pollution and an interaction effect between SSES and real-time PM2·5 levels, as we had predicted.InterpretationOur findings counter the common wisdom that people are motivated to take actions to improve their own environment. Instead, a polluted environment could create a bad norm that undermines trust and environmental protection.FundingPartial funding came from a seed grant for the Chinese University of Hong Kong (CUHK)—Chinese Academy of Social Sciences (CASS) Research Collaboration on Social Psychology offered by the Research Committee of CUHK.
P14.04 10 years of weekly web conference for brain tumor of Adolescent/Young Adult (AYA) on behalf of ANOCEF, GO-AJA and SFCE societies
Authors: D Frappaz, C Bronnimann, C Faure Conter, E Vauleon, D Meyronnet, M Sunyach, P Leblond, R Tanguy, V Laurence, A Bonneville-Levard
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The skills of adult versus pediatric neuro-oncologists are not completely similar though additive. Because the tumors and their protocols are different and the tolerance and expected sequelae are specific. Multidisciplinary meetings including adult and pediatric neuro oncologists are warranted to share expertise. MATERIAL AND METHODS Since 2008, on behalf of ANOCEF, GO-AJA and SFCE societies, a weekly national web based conference was held in France. Any patient with the following criteria could be discussed: Adolescent and Young Adults aged between 15 and 25 years, and any adult with a pediatric type pathology, including medulloblastoma, germ cell tumors, embryonic tumors, ependymoma, pilocytic astrocytoma. RESULTS Number of cases discussed increased from 8 to 202/year, with a mean number of 3 cases (1 to 7) discussed at each meeting. In 2018, 36 meetings were held, with a mean of 8 participants (2 to 14) issued from various French centers. 168 cases were discussed in 2018. Mean age was 30 years old (7 to 67). 45% were discussed at diagnosis; The patients had mostly medulloblastomas (n=47), ependymomas (n=24), low (n=21) or high grade gliomas (n=11), pineal tumors (n=20), germ cell tumors (n=9) and embryonal tumors (n=6). The rate of inclusion in protocols was increased since the opening of this web conference, especially for the germ cell tumor GCT SIOP protocol that is opened without age restriction, and in RSMA standard risk or MEVITEM relapse adult medulloblastoma protocols. CONCLUSION Multidisciplinary Web conference for AYAs is feasible and fruitful. It shares knowledge and increases the inclusion rate in protocols. It should be developped further.
Pilot study of NKTR214 and nivolumab in patients with sarcomas.
Authors: Sandra P. D'Angelo, Anthony Paul Conley, Ciara Marie Kelly, Mark Andrew Dickson, Mrinal M. Gounder, Ping Chi, Mary Louise Keohan, J. Andrew Livingston, Shreyaskumar Patel, Travis Adamson, Hannah Kiesler, Matthew Biniakewitz, Haley Phelan, Mercedes M. Condy, Narasimhan P Agaram, Li-Xuan Qin, Joseph Patrick Erinjeri, Sinchun Hwang, William D. Tap
Journal: Journal of Clinical Oncology (2019)

11010 Background: Monotherapy checkpoint inhibitors have minimal efficacy in most patients with metastatic sarcoma. NKTR-214 is a CD122-preferential IL-2 pathway agonist that activates and expands natural killer and CD8+ T cells. Phase I/II data demonstrated the safety and efficacy of nivolumab plus NKTR-214 in multiple tumor types. A trial of NKTR-214 plus nivolumab was initiated in patients with selected sarcomas. Methods: This is a multi-center pilot study enrolling patients (pts) failing prior regimens within 9 cohorts: leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), chondrosarcoma (CS), osteosarcoma (OS), angiosarcoma (AS), alveolar soft part sarcoma (ASPS), synovial sarcoma/small blue round cell and other. Pts received NKTR 0.006mg/kg with nivolumab 360 mg every 3 weeks. Primary endpoint was objective response rate (ORR), secondary endpoints were adverse events (AEs), progression-free, overall survival (PFS,OS) and clinical benefit rate (CBR.) Pre/on treatment biopsies performed on patients for correlative studies including PD-L1 expression and TIL characterization by immunohistochemistry, whole exome sequencing and RNAseq. Results: Enrollment completed with 10 patients in cohorts below. 50 pts enrolled (median age 58, range 14-80), 54% female. Median follow-up time is 13m. 50% of patients were refractory ≥3 lines of therapy. Grade 3/4 treatment related adverse events occurred in 26% of patients. 2% of patients stopped due to AEs. Median time to response was 3.6m. Responses seen in LMS, UPS, dedifferentiated CS; on-going in UPS/CS. Prolonged disease stability in DDLPS. 6 patients remain on treatment. Conclusions: Nivolumab plus NKTR-214 was safe and tolerable in heavily pre-treated and refractory sarcoma patients. Responses were protracted overtime; on-going in UPS and dedifferentiated CS. Prolonged disease stability seen in DDLPS in patients. All correlative analyses are in progress and will be presented. Enrollment continues with plans to add a treatment naïve cohort. Clinical trial information: NCT03282344. [Table: see text]
OS12.5 Small GTPase RHOE/RND3, a new critical regulator of NF-êB signaling in glioblastoma multiforme?
Authors: B Liu, Q Chen
Journal: Neuro-Oncology (2019)

Abstract Background Abnormal activation of NF-κB signaling is a major mechanism of apoptosis resistance in glioblastoma multiforme (GBM). Therefore, better understanding of the regulation of NF-κB signaling has a significant impact for GBM therapy. Here, we uncovered a critical role of the small GTPase RND3 in regulating the p65 subunit of NF-κB and NF-κB signaling in GBM. MATERIALS AND METHODS Human GBM samples, GBM cells and a human orthotopic GBM-xenografted animal model were used. The mechanisms of RND3 in regulation of NF-κB signaling and GBM cell apoptosis were examined by luciferase assay, quantitative PCR, immunostaining, immunoblotting, immunofluorescence, co-immunoprecipitation, TUNEL staining, JC-1 analysis and flow cytometry. RESULTS Overexpression of RND3 led to reduced p65 activity in GBM cultured cells and a GBM animal model, indicating that the NF-κB pathway is negatively regulated by RND3 in GBM. Mechanistically, we found that RND3 bound p65 and promoted p65 ubiquitination, leading to decreased p65 protein levels. Furthermore, RND3 enhanced cleaved-caspase 3 levels and promoted apoptosis in GBM cells, and RND3 expression was positively correlated with cleaved-caspase 3 and IL-8 in human GBM samples. The effect of RND3 on promoting apoptosis disappeared when p65 ubiquitination was blocked by protease inhibitor carfilzomib or upon co-expression of ectopic p65. CONCLUSION RND3 binds p65 protein and promotes its ubiquitination, resulting in reduced p65 protein expression and inhibition of NF-κB signaling to induce GBM cell apoptosis.