tbuckley/cabot-search huggingface dataset:
Exposure to injury in mixed-martial-arts is associated with evidence of concussion injury
Authors: Christopher Neville, Paul Johnson, Joshua Baracks, Brian Rieger
Journal: British Journal of Sports Medicine (2017)

Objective The purpose of this study was to determine if exposure to injury during mixed-martial-arts (MMA) fights is associated with concussion injury. It was hypothesised that number of hits-to-the-head (HTH) would be associated with concussion assessment findings. Design Case-series Setting Amateur MMA fighters agreed to complete the testing at training facilities and fight venues. Participants A convenience sample 33 MMA fighters completed pre and post-fight assessments (32 males, 1 female) Interventions (or Assessment of Risk Factors) The independent variable was group assignment. The low-exposure (LE) group (n=17) had a mean of 5.8±5.9 HTH while the high-exposure (HE) group (n=16) had a mean of 34.0±9.8 HTH. Outcome measures The dependent variables were compared using an ANOVA model. They included: average speed to complete the Tails B cognitive test, balance measured with an inertial measurement unit, S100B protein concentration in blood serum, and self-reported symptoms. Main results The change in S100B concentration from pre to post-fight was significantly greater (p=0.01) in the HE group (0.22±0.14 ug/L) compared to the LE group (0.10±0.11 ug/L). Dual-task balance cost was significantly greater (p=0.02) in the HE group (0.04±0.05 m/s 2 /Hz) compared to the LE (0.01±0.01 m/s 2 /Hz) group. No difference in Trails B speed or self-reported symptoms was observed. Conclusions The increase in S100B concentration in the peripheral blood and changes in balance performance suggest concussion injuries are common during MMA fights but injuries are associated with exposure to head impacts. Cognitive tests and symptom report may not be as sensitive to injury. Competing interests Dr. Neville: Ongoing research sponsorship and equity interest in Motion Intelligence Inc. who provided the hardware for some of the concussion screening used in this study. Dr. Johnson: None. Mr. Baracks: None. Dr. Rieger: Ongoing research sponsorship and equity interest in Motion Intelligence Inc. who provided the hardware for some of the concussion screening used in this study.
Maternal age and severe maternal morbidity: A population-based retrospective cohort study
Authors: Sarka Lisonkova, Jayson Potts, Giulia M. Muraca, Neda Razaz, Yasser Sabr, Wee-Shian Chan, Michael S. Kramer
Journal: PLoS Medicine (2017)

One of the United Nations' Millennium Development Goals of 2000 was to reduce maternal mortality by 75% in 15 y; however, this challenge was not met by many industrialized countries. As average maternal age continues to rise in these countries, associated potentially life-threatening severe maternal morbidity has been understudied. Our primary objective was to examine the associations between maternal age and severe maternal morbidities. The secondary objective was to compare these associations with those for adverse fetal/infant outcomes.
Identification of comprehensive geriatric assessment based risk factors for malnutrition in elderly Asian patients with cancer.
Authors: Tira Jing Ying Tan, Whee Sze Ong, Khai-Nee Koo, Iain B. Tan, Donald Poon, Ravindran Kanesvaran
Journal: Journal of Clinical Oncology (2013)

9552 Background: Elderly patients with cancer are at increased risk for poor nutrition. Malnutrition is associated with increased morbidity and mortality. There is limited information on the clinical risk factors for malnutrition in elderly Asian cancer patients. We aim to identify comprehensive geriatrics assessment (CGA) based clinical factors in elderly Asian cancer patients associated with an increase in malnutrition risk. Methods: CGA data was collected from 249 Asian patients aged 70 years or older who attended the outpatient oncology clinics at the National Cancer Centre Singapore. Nutritional status, one of the seven domains of CGA, was assessed based on the DETERMINE nutritional risk index. Univariate and multivariate logistic regression analyses were applied to assess the association between patient clinical factors together with domains within the CGA and moderate to high nutritional risk. Goodness of fit was assessed using Hosmer-Lemeshow test and discrimination ability assessed based on the area under the receiver operating characteristics curve (AUC). Internal validation was performed using simulated datasets via bootstrapping. Results: Among the 249 patients, 184 (74%) had moderate to high nutritional risk. Multivariate logistic regression analysis identified stage 3–4 disease (Odds Ratio [OR] 2.54; 95% CI, 1.14-5.69), ECOG performance status of 2-4 (OR 3.04; 95% CI, 1.57–5.88), presence of depression as measured by geriatric depression scale (OR 5.99; 95% CI, 1.99-18.02) and haemoglobin levels &lt;12 g/dL (OR 3; 95% CI 1.54-5.84) as significant independent factors associated with moderate to high nutritional risk. The model achieved good calibration (Hosmer-Lemeshow test’s p = 0.17) and discrimination (AUC = 0.80). It retained good calibration and discrimination (bias-corrected AUC = 0.79) under internal validation. Conclusions: Having advanced stage of cancer, poor performance status, depression and anaemia were found to be independent predictors of moderate to high nutritional risk. Early identification of patients with these risk factors will allow for nutritional interventions which may improve treatment tolerance, quality of life and survival outcomes.
Allergen immunotherapy for allergic asthma: A systematic review and meta‐analysis
Authors: S. Dhami, A. Kakourou, F. Asamoah, I. Agache, S. Lau, M. Jutel, A. Muraro, G. Roberts, C. A. Akdis, M. Bonini, O. Cavkaytar, B. Flood, P. Gajdanowicz, K. Izuhara, Ö. Kalayci, R. Mosges, O. Palomares, O. Pfaar, S. Smolinska, M. Sokolowska, M. Asaria, G. Netuveli, H. Zaman, A. Akhlaq, A. Sheikh
Journal: Allergy (2017)

Abstract Background To inform the development of the European Academy of Allergy and Clinical Immunology's ( EAACI ) Guidelines on Allergen Immunotherapy ( AIT ) for allergic asthma, we assessed the evidence on the effectiveness, cost‐effectiveness and safety of AIT . Methods We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random‐effects meta‐analyses. Results 98 studies satisfied the inclusion criteria. Short‐term symptom scores were reduced with a standardized mean difference ( SMD ) of −1.11 (95% CI −1.66, −0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short‐term medication scores were reduced SMD −1.21 (95% CI −1.87, −0.54), again with evidence of potential publication bias. There was no reduction in short‐term combined medication and symptom scores SMD 0.17 (95% CI −0.23, 0.58), but one study showed a beneficial long‐term effect. For secondary outcomes, subcutaneous immunotherapy ( SCIT ) improved quality of life and decreased allergen‐specific airway hyperreactivity ( AHR ), but this was not the case for sublingual immunotherapy ( SLIT ). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR . AIT resulted in a modest increased risk of adverse events ( AE s). Although relatively uncommon, systemic AE s were more frequent with SCIT ; however no fatalities were reported. The limited evidence on cost‐effectiveness was mainly available for sublingual immunotherapy ( SLIT ) and this suggested that SLIT is likely to be cost‐effective. Conclusions AIT can achieve substantial reductions in short‐term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AE s. More data are needed in relation to secondary outcomes, longer‐term effectiveness and cost‐effectiveness.
PIK3CA hotspot mutations differentially impact responses to MET targeting in MET-driven and non-driven preclinical cancer models
Authors: Lluís Nisa, Pascal Häfliger, Michaela Poliaková, Roland Giger, Paola Francica, Daniel Matthias Aebersold, Roch-Philippe Charles, Yitzhak Zimmer, Michaela Medová
Journal: Molecular Cancer (2017)

The MET receptor tyrosine kinase represents a promising target in cancer. PIK3CA activating mutations are common in several tumor types and can potentially confer resistance to anti-receptor tyrosine kinase therapy.MET and/or PI3K pathway inhibition was assessed in NIH3T3 cells harboring MET-activating point mutation with or without ectopic expression of PIK3CAE545K and PIK3CAH1047R, as well as in MET-expressing head and neck cancer cells with endogenous PIK3CA mutations. Endpoints included PI3K pathway activation, cell proliferation, colony-forming ability, cell death, wound-healing, and an in vivo model.PIK3CAE545K and PIK3CAH1047R confer resistance to MET inhibition in MET-driven models. PIK3CAH1047R was more potent than PIK3CAE545K at inducing resistance in PI3K pathway activation, cell proliferation, colony-forming ability, induction of cell death and wound-healing upon MET inhibition. Resistance to MET inhibition could be synergistically overcome by co-targeting PI3K. Furthermore, combined MET/PI3K inhibition led to enhanced anti-tumor activity in vivo in tumors harboring PIK3CAH1047R. In head and neck cancer cells the combination of MET/PI3K inhibitors led to more-than-additive effects.PIK3CA mutations can lead to resistance to MET inhibition, supporting future clinical evaluation of combinations of PI3K and MET inhibitors in common scenarios of malignant neoplasms featuring aberrant MET expression and PIK3CA mutations.
Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination
Authors: Hong Jiang, Yisel Rivera-Molina, Candelaria Gomez-Manzano, Karen Clise-Dwyer, Laura Bover, Luis M. Vence, Ying Yuan, Frederick F. Lang, Carlo Toniatti, Mohammad B. Hossain, Juan Fueyo
Journal: Cancer Research (2017)

Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor, and reactivate antitumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune costimulator OX40 ligand (OX40L). Like its predecessor Delta-24-RGD, Delta-24-RGDOX induced immunogenic cell death and recruit lymphocytes to the tumor site. Compared with Delta-24-RGD, Delta-24-RGDOX exhibited superior tumor-specific activation of lymphocytes and proliferation of CD8
IMMU-12. IMMUNOTHERAPY OF WILMS TUMOR 1 PEPTIDE VACCINATION IMPROVE PROGNOSIS OF RECURRENT GLIOBLASTOMA AND DIFFUSE INTRINSIC PONTINE GLIOMA IN CHILDREN
Authors: Naoki Kagawa, Yoshiko Hashii, Ryuichi Hirayama, Yasuyoshi Chiba, Hideyuki Arita, Chisato Yokota, Takamune Achiha, Noriyuki Kijima, Yasunori Fujimoto, Naoya Hashimoto, Haruo Sugiyama, Toshiki Yoshimine
Journal: Neuro-Oncology (2017)

BACKGROUND: We have ever proven safety and effectiveness of Wilms tumor 1 peptide (WT1) vaccination for newly-diagnosed or recurrent glioblastomas (GBM) in adult. But pediatric GBM and diffuse intrinsic pontine glioma (DIPG) are known to differ from adult GBM biologically. A pilot study designed to investigate safety and effectiveness of Wilms tumor 1 peptide vaccination for recurrent GBM and DIPG in children was planned. PATIENTS AND METHODS: HLA-A*2402–positive five children with recurrent malignant glioma (three spratentorial GBMs and two DIPGs) were registered in this clinical study of WT1 immunotherapy. In all children, the tumors were resistant to standard therapy including radiation and temozolomide. Patients received intradermal injections of an HLA-A*2402–restricted, WT1 peptide every week for 12 weeks. Patients with an effective response continued to be vaccinated until tumor progression occurred or performance status deteriorated. Tumor responses were evaluated based on MRI data by RANO (Response Assessment in Neuro-Oncology) criteria. Progression-free survival and overall survival after initial WT1 treatment were analysed. RESULTS: In all patients, no severe adverse event was observed. The protocol was well tolerated in children. The 6-month progression-free survival rate was 40%. Progression-free survival and overall survival were significantly improved as compared with historical control in Osaka University Hospital. Two patients with supratentorial GBM are still alive more than three years. CONCLUSIONS: This study showed that WT1 vaccine therapy against recurrent GBM and DIPG in HLA-A*2402–positive children was safe and improved their prognosis. Based on these results, further clinical studies of WT1 immunotherapy in children suffering from newly diagnosed or recurrent malignant glioma should be authorized.
The association of objective response and overall survival in patients with inoperable or metastatic gastric and esophagogastric junction (EGJ) cancer: A pooled analysis of individual patient data from first-line clinical trials.
Authors: Toki Anna Bolt, Claudia Pauligk, Dominique Werner, Frank Mayer, Ralf Dieter Hofheinz, Nils Homann, Kim Luley, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2013)

4095 Background: The aim of the study is to determine whether the achievement of an objective response to first-line chemotherapy is prognostic of patient’s outcome in gastric/EGJ adenocarcinoma. Methods: Individual patient (pts) data from prospective first-line trials conducted by a single study group were used. Patients received platin/5-FU based chemotherapy with or without docetaxel. Responses were evaluated according to WHO criteria in all trials. Response data, patients’ characteristics (age, sex, entity, histological type, primary location, ECOG PS, and type and number of metastatic sites), type of chemotherapy, and overall survival data were analyzed. Results: 612 pts were included. Median age was 66 yrs; 31.5% had ECOG status 0, 58.3% ECOG 1, and 9.8% ECOG 2 &amp; 3. Gastric primaries were found in 44.4% and EGJ in 35.8% of pts (19.7% were overlapping/not evaluable). According to Lauren classification, 36.8% had intestinal, 32.4% diffuse, and 8.5% mixed types (22.4% were not classifiable). 64.5% had positive non-regional lymph nodes (LN) involvement, 14.1% LN involvement without other metastases, 33.3% had peritoneal carcinomatosis, 44.0% liver and 16.7% lung metastases. Response rates were complete (CR) in 3.1%, partial (PR) in 36.4%, stable disease (SD) in 34.5%, and progressive disease (PD) in 15.0% pts (10.9% were not evaluable). Overall response rate (OR; CR + PR) was 39.5%. Median overall survival times in pts with CR vs PR vs SD vs PD were 37.9 vs 14.7 vs 10.9 vs 5.2 months, respectively; p=1.26 x 10 -33 ). OR (CR or PR) also strongly predicted OS (16.7 vs 8.1 months in pts with vs no OR, p=1.08 x 10 -17 ). OR remained the strongest predictor of OS in the multivariate analysis (p=6.55 x 10 -7 ) including all baseline criteria mentioned above followed by ECOG PS (p=0.048) and the presence of non-regional LN as the only site of metastasis (p=0.034). Conclusions: The achievement of an objective response is the strongest predictor of survival in pts with gastric and EGJ cancer and could serve as a surrogate marker if validated.
LGG-04. CHARACTERIZATION OF ONCOGENE-INDUCED SENESCENCE AND THE ROLE OF THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE IN PILOCYTIC ASTROCYTOMA
Authors: Juliane Hohloch, Florian Selt, Thomas Hielscher, Felix Sahm, David Capper, Diren Usta, Jonas Ecker, Ina Oehme, Cornelis M. van Tilburg, Andreas von Deimling, Martin U. Schuhmann, Andrey Korshunov, David T.W. Jones, Tilman Brummer, Stefan M. Pfister, Olaf Witt, Till Milde
Journal: Neuro-Oncology (2017)

The benign but unpredictable growth behaviour of pilocytic astrocytoma (PA) is thought to originate from variations in proliferation caused by oncogene-induced senescence (OIS). An increase in MAPK pathway activation, present in virtually all PAs, serves a stimulus driving the tumor into OIS. Upregulation of p16, p21 and several other OIS-related genes has been observed in primary PAs. The secretion of a set of cytokines, growth factors and proteases, referred to as the senescence-associated secretory phenotype (SASP), is a characteristic feature of senescent cells. The SASP is thought to be involved in the induction and maintenance of the OIS state. The key SASP factors in PA and their functional significance are unknown. To study OIS in PA, the genetically engineered primary PA cell culture model DKFZ-BT66 was used. The model allows switching between senescence and proliferation via inducible expression of the SV40 Large T Antigen suppressing p53/RB signaling. Readouts used were gene-expression profiling (GEP), Western Blot, real-time qPCR, ELISA, cell counts and viability by automated trypan blue exclusion staining. Comparison of the GEP of senescent versus proliferating cells showed a significant increase in the SASP during OIS. The upregulation of the representative SASP factors IL-6 and IL-1B was confirmed on mRNA and protein level. The respective receptor proteins were both expressed, and activation of both pathways was detected in the OIS state. Stimulation of selected SASP pathways led to reduced cell growth of proliferating cells. In summary, the first representative patient-derived PA tumor model DKFZ-BT66 confirms the presence of OIS in PA, and additionally reveals activity of the OIS-characteristic SASP. Ongoing studies will show whether the OIS-induced growth arrest is reversible and if it may explain the unpredictable regrowth of PAs observed in patients. These findings will be relevant for treatment decisions concerning anti-inflammatory or immunosuppressive drugs in PA patients.
Cognitive architecture enables comprehensive predictive models of visual search
Authors: David E. Kieras, Anthony Hornof
Journal: Behavioral and Brain Sciences (2017)

Abstract With a simple demonstration model, Hulleman &amp; Olivers (H&amp;O) effectively argue that theories of visual search need an overhaul. We point to related literature in which visual search is modeled in even more detail through the use of computational cognitive architectures that incorporate fundamental perceptual, cognitive, and motor mechanisms; the result of such work thus far bolsters their arguments considerably.
The Myth of Patient Centeredness in the Trauma Bay
Authors: Stacy B. Sanders, Heena P. Santry
Journal: JAMA Surgery (2017)

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Experience with canada’s first school-based concussion policy, and overall evaluation using a modified delphi methods
Authors: Swapna Mylabathula, Tator Charles
Journal: British Journal of Sports Medicine (2017)

Objective Ontario is the first province in Canada to implement a school-based concussion policy, Policy/Program Memorandum (PPM) 158. It requires all public school boards to develop a concussion strategy. The aim of this research was to conduct a pilot assessment of PPM 158 implementation in one large school board, and then to develop a novel policy evaluation tool to evaluate how well all 72 school board concussion strategies align with best practices identified through a modified Delphi method. Design Descriptive. Setting Ontario public school boards (n=72). Participants and main results In the pilot assessing PPM 158 implementation, there were 39 respondents of 109 high school principals in the Toronto District School Board (TDSB). 92% of schools provided education to students in the TDSB, and fewer educated staff (85%) or parents (43.6%). Most schools had return-to-play protocols (92%) and fewer had return-to-learn protocols (77%). Outcome measures As a result of the pilot study, it was decided to develop the following outcome measures: stakeholder concussion education for staff, parents and students; mode of education; and existence of return-to-play and return-to-learn protocols. Policy evaluation will comprise the following: score achieved on the policy evaluation tool to be developed through a modified Delphi method, which reflects how each policy compares with best practices recommendations. Conclusions Significant progress has been made in developing school-based concussion in the single board assessed, but there are deficiencies in certain areas of implementation. This research has informed policies that target childhood concussions in Ontario and beyond. Competing interests None.
IMMU-20. SELECTING AN EPHA2-CAR FOR THE IMMUNOTHERAPY OF DIPG AND GBM
Authors: Brooke Prinzing, Zhongzhen Yi, Kevin Chow, Stephen Gottschalk, Giedre Krenciute
Journal: Neuro-Oncology (2017)

The intent of this project is to develop T cells expressing an EphA2-specific chimeric antigen receptor (CAR) as an immunotherapy for diffuse intrinsic pontine glioma (DIPG) and glioblastoma (GBM). EphA2 is an attractive target given its high expression in GBM but not normal brain tissue. We previously generated an EphA2-specific CAR that exhibited potent antitumor activity in a glioma xenograft model. However, this CAR had a CH2CH3 spacer, which binds FC receptors and is not ideal for clinical development. We therefore generated a panel of EphA2-CARs with a short spacer region (SSR) lacking FC receptor binding sites, and a CD28.ζ, CD137.ζ, or CD28.CD137.ζ endodomain. T cell transduction efficiency ranged from 60–80%. CAR T cells only killed EphA2+ target cells (U373, A549), secreted IFNγ and IL2 in an antigen-dependent manner, and expanded for at least 14 days after repeat stimulations with EphA2+ tumor cells with no significant difference between CAR T-cell lines. In vivo, intratumoral injection of CD28.ζ and CD137.ζ CAR T cells in the U373 glioma model provided complete responses in 40–100% of mice at cell doses of 2x106, 5x105, or 1x105, but exhibited only transient antitumor activity at the lowest cell dose of 1x104. Comparing persistence of CD28.ζ and CD137.ζ CAR T cells after intratumoral injection in vivo revealed no significant difference. We demonstrate here that CD28.ζ and CD137.ζ EphA2-CAR T cells have similarly potent antitumor activity, and that including a second costimulatory domain does not improve effector function. We selected CD28.ζ EphA2-CARs for future clinical development since CD28.ζ CAR T cells do not persist long-term in humans. While our CAR’s scFV recognizes a cancer-specific conformational epitope, we are including an inducible suicide gene for clinical grade vector production. Limited T-cell persistence should further reduce the inherent risk of ‘on target/off cancer toxicity’ in a ‘first-in-human’ clinical study.