tbuckley/cabot-search huggingface dataset:
The Sport Concussion Assessment Tool 5th Edition (SCAT5): Background and rationale
Authors: Ruben J Echemendia, Willem Meeuwisse, Paul McCrory, Gavin A Davis, Margot Putukian, John Leddy, Michael Makdissi, S John Sullivan, Steven P Broglio, Martin Raftery, Kathryn Schneider, James Kissick, Michael McCrea, Jiří Dvořák, Allen K Sills, Mark Aubry, Lars Engebretsen, Mike Loosemore, Gordon Fuller, Jeffrey Kutcher, Richard Ellenbogen, Kevin Guskiewicz, Jon Patricios, Stanley Herring
Journal: British Journal of Sports Medicine (2017)

This paper presents the Sport Concussion Assessment Tool 5th Edition (SCAT5), which is the most recent revision of a sport concussion evaluation tool for use by healthcare professionals in the acute evaluation of suspected concussion. The revision of the SCAT3 (first published in 2013) culminated in the SCAT5. The revision was based on a systematic review and synthesis of current research, public input and expert panel review as part of the 5th International Consensus Conference on Concussion in Sport held in Berlin in 2016. The SCAT5 is intended for use in those who are 13 years of age or older. The Child SCAT5 is a tool for those aged 5-12 years, which is discussed elsewhere.
Contents, Vol. 31, 1979
Authors: Chase Patterson Kimball, Linford Rees, H. Musaph, David Shapiro, Robert G. Priest, Hellmuth Freyberger, Samuel A. Corson, Elizabeth O'Leary Corson, Paul Chauchard, Wilfred Dorfman, J.J. Groen, R.A. Ramsay, A.J. Krakowski, E.D. Wittkower, F. Engelsmann, Hoyle Leigh, Morton F. Reiser, Tetsuya Nakagawa, Yufiro Ikemi, Adolf-Ernst Meyer, Wolfram Schüffel, Ulrich Egle, Ulrich Schairer, Aegidius Schneider, Nicholas Destounis, Adam J. Krakowski, Renata Gaddini, Mauricio Knobel, Albert J. Silverman, L. Miller de Paiva, H. Nakao, Luigi Oreste Speciani, Günter Ammon, Jan Pohl, Yukihiro Ago, Hideki Teshima, Shoji Nagata, Sadahisa Inoue, Yujiro Ikemi, Y. Nakai, M. Sugita, T. Nakagawa, T. Araki, Y. Ikemi, Jacob Shanon, M. von Rad, M. Drücke, W. Knauss, F. Lolas, Hubert Speidel, Uwe Koch, Friedrich Balck, Jörg Kniess, J. Bastiaans, W. Bräutigam, Norman B. Levy, R. Lohmann, B. Voges, F. Meuter, K.U. Rath, W. Thomas, Cairns Aitken, Hans Molinski, H. Huebschmann, Milton V. Kline, B. Luban-Plozza, J. Suzuki, Y. Yamauchi, H. Yamamoto, U. Komuro, Morton F. Reiser, Yujiro Ikemi, Hitoshi Ishikawa, Johanna Margaretha Tamm, Keigo Okonogi, Hiroshi Iwai, Hitoshi Ishikawa, Tadanobu Tsunoda, John R.M. Goyeche
Journal: Psychotherapy and Psychosomatics (1979)
Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment
Authors: Anthony Burgos-Robles, Eyal Y Kimchi, Ehsan M Izadmehr, Mary Jane Porzenheim, William A Ramos-Guasp, Edward H Nieh, Ada C Felix-Ortiz, Praneeth Namburi, Christopher A Leppla, Kara N Presbrey, Kavitha K Anandalingam, Pablo A Pagan-Rivera, Melodi Anahtar, Anna Beyeler, Kay M Tye
Journal: Nature Neuroscience (2017)
Preclinical assessment of a fixed dose combination of novel liposome formulations of idarubicin and gemcitabine showing improved antitumor activity
Authors: Nancy Dos Santos, Alexander Van Hecke, Dana Masin, Marcel B. Bally
Journal: Cancer Research (2005)

1406  Objective: Combination chemotherapy regimens are the mainstay of cancer treatment. In general, established protocols utilizing drug combinations are empirically defined in late phase clinical trials. There is a need to identify effective drug combinations during preclinical studies. The purpose of the studies described herein was to achieve improved therapeutic activity by combining idarubicin (IDA) and gemcitabine (GEM). These drugs were chosen based on their complementary antitumor effects, non-overlapping toxicities and proven efficacy. It is further proposed that the therapeutic properties of the individual drugs will be enhanced when administered in appropriately selected liposomal formulations. The studies established a method to define a fixed dose combination product administered in preclinical animal models at doses selected on the basis of the toxic and therapeutic effects of the individual drugs, whether given alone or in a liposomal formulation. Methods: Combination drug treatments were prepared at drug/drug ratios defined on the basis of maximum tolerable dose (MTD) studies. The efficacy of the combination drug product comprised of free and/or liposomal drugs was then determined at three effective doses in a murine leukemia model. Results: In vitro cytotoxicity data, where combination effects were determined for several different drug/drug ratios, indicated that GEM and IDA exhibited moderate to strong synergism over a broad range of effective doses. A GEM lipid formulation was established in DSPC / Cholesterol / DSPE-PEG2000 (50:45:5 mole ratio). This lipid formulation significantly increased plasma drug circulation lifetimes (T1/2 = 14.3 h) when compared to free GEM (T1/2 = 2.1 h). Similarly, encapsulation of idarubicin in DSPC / DSPE-PEG2000 (98:2 mole ratio) significantly increased plasma drug circulation lifetimes (T1/2 = 6.7) when compared to free IDA (T1/2 = 1.2 h). The combination treatment of liposomal IDA (2 mg/kg) and liposomal GEM (3.4 mg/kg), evaluated in a murine leukemia model, resulted in a 281 % increase in life span (% ILS), yielding a synergistic effect as judged when compared to liposomal IDA (2 mg/kg; 156 % ILS) and liposomal GEM (5 mg/kg; 100 % ILS) administered as single agents. Interestingly, when IDA (2 mg/kg) and GEM (334 mg/kg) were administered as a combination of free drugs, a much lower (125 %) ILS was observed. Conclusions: The combination of IDA and GEM in vitro demonstrated synergistic cytotoxic activity over a broad range of concentrations. In a murine leukemia model, appropriate drug/drug ratios were chosen based on the MTD of a single dose administration for each drug. The combination of the liposomal drugs yielded synergistic % ILS, which was not observed for free/free or free/liposomal drug combinations.
Low LDL cholesterol,<i>PCSK9</i>and<i>HMGCR</i>genetic variation, and risk of Alzheimer’s disease and Parkinson’s disease: Mendelian randomisation study
Authors: Marianne Benn, Børge G Nordestgaard, Ruth Frikke-Schmidt, Anne Tybjærg-Hansen
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis<i></i>(<i>PCSK9</i> and 3-hydroxy-3-methylglutaryl-CoA reductase (<i>HMGCR</i>), respectively) is associated with a high risk of Alzheimer’s disease, vascular dementia, any dementia, and Parkinson’s disease in the general population. <b>Design</b>&nbsp;Mendelian randomisation study. <b>Setting</b>&nbsp;Copenhagen General Population Study and Copenhagen City Heart Study. <b>Participants</b>&nbsp;111 194 individuals from the Danish general population. <b>Main outcome measures</b>&nbsp;Risk of Alzheimer’s disease, vascular dementia, all dementia, and Parkinson’s disease. <b>Results</b>&nbsp;In observational analyses, the multifactorially adjusted hazard ratio for Parkinson’s disease in participants with an LDL cholesterol level &lt;1.8 mmol/L versus ≥4.0 mmol/L was 1.70 (95% confidence interval 1.03 to 2.79), whereas the corresponding hazard ratios for Alzheimer’s disease, vascular dementia, or any dementia did not differ from 1.0. <i>PCSK9</i> and <i>HMGCR</i> variants combined were associated with a 9.3% lower LDL cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of birth, the risk ratios for a lifelong 1 mmol/L lower LDL cholesterol level were 0.57 (0.27 to 1.17) for Alzheimer’s disease, 0.81 (0.34 to 1.89) for vascular dementia, 0.66 (0.34 to 1.26) for any dementia, and 1.02 (0.26 to 4.00) for Parkinson’s disease. Summary level data from the International Genomics of Alzheimer’s Project using Egger Mendelian randomisation analysis gave a risk ratio for Alzheimer’s disease of 0.24 (0.02 to 2.79) for 26 <i>PCSK9</i> and <i>HMGCR</i> variants, and of 0.64 (0.52 to 0.79) for 380 variants of LDL cholesterol level lowering. <b>Conclusion</b>&nbsp;Low LDL cholesterol levels due to <i>PCSK9</i> and <i>HMGCR</i> variants had no causal effect on high risk of Alzheimer’s disease, vascular dementia, any dementia, or Parkinson’s disease; however, low LDL cholesterol levels may have a causal effect in reducing the risk of Alzheimer’s disease.
P09.05 Treatment outcomes in young patients with glioblastoma: the Cleveland Clinic experience
Authors: S. Mohapatra, A. Choi, K. Braun, E. Murphy, S. Chao, J. Suh, G. Stevens, D. Peereboom, J. Xuefei, M. S. Ahluwalia
Journal: Neuro-Oncology (2017)

Introduction: Fifty percent of glioblastoma patients are < 65 years old. We report our experience with younger patients with glioblastoma treated our tertiary care center. Materials and Methods: With IRB approval, the Cleveland Clinic’s database was used to identify glioblastoma patients treated through 2000 - 2015. Overall survival (OS) from the diagnosis of glioblastoma was the primary end point. Cox proportional hazard models with stepwise variable selections were used for data analysis. Results: 598 patients whose age were less than 65 years old were analyzed. The estimated median survival was 14 months, and the 1-year survival was 60.9% ± 2.0%, the 2-year survival was 25.5% ± 1.8% and 5-year survival was 2.3% ± 0.7%. The estimated median progression-free survival (PFS) was 7 months, and the 1-year PFS was 31.3% ± 1.9%, the 2-year PFS was 11.6% ± 1.3% and 5-year PFS was 0.6% ± 0.3%. The OS and PFS were found to be different between treatment groups.: Compared to the RT treatment only group, the RT+chemo group and chemo group were had a significantly better OS and PFS, and the results hold true with the adjustment of other facts in the multivariable analysis. 93.1% of patients had 1st line treatment; 57.5% of patients had 2nd line treatment; and 37.1% of patients had 3rd line treatment. The MGMT mutation had a significant associated with overall survival and a marginal association with progression-free survival. That is patients with MGMT mutation had a low risk of death/progression compared to those without MGMT. Compared to biopsy only surgery, GTR and STR had a significantly lower risk of death/progression with /without the adjustment of other factors. Patients whose age were between 50 -55 had no different OS and PFS compared to age < 50; age between 56-60 had a higher risk of death or progression compared to 50-55 group. And age between 60-65 had no different than the group between 65 – 60. Conclusions: Aggressive treatment with chemoradiation is associated with better outcomes in younger GBM, particularly in MGMT methylated population.
P05.01 Anhidrosis in neurohypophyseal germinoma
Authors: K. Adachi, S. Ansai, Y. Igarashi, Y. Matano, T. Kitamura, A. Morita
Journal: Neuro-Oncology (2017)

INTRODUCTION: Acquired generalized anhidrosis (AGA) is the disease with non-congenital, non-segmented diffuse sweating dysfunction and is associated with neurological signs and dysautonomia except for anhidrosis. Here we have experienced 2 cases of AGA in the patient with neurohypophyseal germinoma after carboplatin (CBDCA) plus etoposide (VP-16) (CARE) therapy. Relationship of AGA to neurohypophyseal germinomas and their treatment is discussed. CASES: We experienced two young (26 y/o and 27 y/o) female neurohypopheseal germinoma cases of anhidrosis. They received CARE as chemotherapy and whole ventricular irradiation. They showed heat retension 2 to 3 years after initial treatment without recurred germinoma. Because acetylcholine sweating test was negative and skin biopsy revealed normal sweat gland structure, the diagnosis of acquired idiopathic generalized anhidrosis (AIGA), idiopathic pure sudomotor failure subtype, was initially made. After steroid pulse therapy, sweat function recovered partially and completely. DISCUSSION: AIGA and germinoma are both rare diseases. So, the present 2 cases had similar clinical settings, that anhidrosis may not be idiopathic but secondary. Affected responsible site of anhidrosis in the present cases was thought to be acetylcholine receptor in the sweat cells. The present cases did not have any known disease with anhidrosis and did not receive any medication which cause anhidrosis written in the statement of the virtues of a medicine. Commonly used drugs in both cases were infusion solutions, CARE and related drugs, hormone stimulating test agents. Recently anhidrosis was reported in a case of cancer of unknown primary tumor site after using CBDCA and paclitaxel. Both of the present cases were used CBDCA, which may cause anhidrosis. CONCLUSION: CBDCA may attributed to the occurrence of AGA based on hypothalamic vulnerability.
Amelioration of amyloid-β-induced deficits by DcR3 in an Alzheimer’s disease model
Authors: Yi-Ling Liu, Wei-Ting Chen, Yu-Yi Lin, Po-Hung Lu, Shie-Liang Hsieh, Irene Han-Juo Cheng
Journal: Molecular Neurodegeneration (2017)

Microglia mediate amyloid-beta peptide (Aβ)-induced neuroinflammation, which is one of the key events in the pathogenesis of Alzheimer's disease (AD). Decoy receptor 3 (DcR3)/TNFRSF6B is a pleiotropic immunomodulator that promotes macrophage differentiation toward the M2 anti-inflammatory phenotype. Based on its role as an immunosupressor, we examined whether DcR3 could alleviate neuroinflammation and AD-like deficits in the central nervous system. We crossed human APP transgenic mice (line J20) with human DcR3 transgenic mice to generate wild-type, APP, DcR3, and APP/DcR3 mice for pathological analysis. The Morris water maze, fear conditioning test, open-field, and elevated-plus maze were used to access their cognitive behavioral changes. Furthermore, the pathological and immune profiles were examined by immunostaining, ELISA, Q-PCR, and IP. In vitro assays were designed to examine DcR3-mediated innate cytokine profile alteration and the potential protective mechanism. We reported that DcR3 ameliorates hippocampus-dependent memory deficits and reduces amyloid plaque deposition in APP transgenic mouse. The protective mechanism of DcR3 mediates through interacting with heparan sulfate proteoglycans and activating IL-4+YM1+ M2a-like microglia that reduces Aβ-induced proinflammatory cytokines and promotes phagocytosis ability of microglia. The neuroprotective effect of DcR3 is mediated via modulating microglia activation into anti-inflammatory M2a phenotype, and upregulating DcR3 expression in the brain may be a potential therapeutic approach for AD.
Web-based cognitive behavioural therapy blended with face-to-face sessions for chronic fatigue in type 1 diabetes: a multicentre randomised controlled trial
Authors: Juliane Menting, Cees J Tack, Arianne C van Bon, Henry J Jansen, Joop P van den Bergh, Marc J T M Mol, Martine M Goedendorp, Rogier Donders, Hans Knoop
Journal: The Lancet Diabetes & Endocrinology (2017)
P01.37 Impact of C/EBPβ isoforms on brain tumor initiating cells
Authors: A. Vollmann-Zwerenz, S. Sponton, B. Jachnik, P. Weigell, J. Lorenz, M. Schulze, U. Bogdahn, M. J. Riemenschneider, P. Hau
Journal: Neuro-Oncology (2017)

BACKGROUND: The transcription factor C/EBPβ has been identified as a master regulator of the mesenchymal phenotype in malignant glioma. It is transcribed from an intronless gene, but can be translated into three isoforms (LAP, LAP*, LIP). C/EBPβ has been shown to be upregulated in mesenchymal GBMs and its expression correlates to a worse prognosis in patients. Downregulation of C/EBPβ reduces proliferation and migration in vitro and diminishes tumor growth in vivo. In addition, C/EBPβ protein levels are increased in hypoxic and necrotic areas in human GBM tissue samples. However, expression levels and impact of the different isoforms in glioma are unknown. Crosstalk of C/EBPβ and TFGβ has been shown to influence metastatic behavior of breast carcinoma cells. The aim of this project is therefore to investigate the impact of C/EBPβ isoforms LAP and LIP on phenotype, proliferation and migration of brain tumor initiating cells (BTICs) and their possible interaction with transforming growth factor beta (TGFβ). Methods: LAP and LIP isoforms were stably overexpressed in a set of proneural and mesenchymal BTIC lines. Marker expression was investigated by immunocytochemistry and Western blot. Proliferation was monitored by crystal violet staining and migration by spheroid assay. Genome wide transcriptome analysis was performed by next generation RNA sequencing on a HiSeq (Illumina). Results: Overexpression of LAP ­(full-length protein) induced proneural BTICs to switch towards a mesenchymal phenotype, whereas overexpression of LIP had no such effect. Increased LAP led to enhanced migration in the majority of cell lines irrespective of subtype, whereas LIP mostly decreased migration. Rather the reverse effect was observed regarding proliferation. RNASeq analysis revealed highly differential consequences of LAP and LIP overexpression regarding expressed genes and principal component analysis. TGFβ signaling proved to be one of the most significantly altered pathways both in LAP and LIP cells. However, TGFβ treatment had either no effect or inhibited proliferation or migration independent of C/EBPβ isoform levels. Conclusions: We could show for the first time that overexpression of C/EBPβ is sufficient to induce a mesenchymal phenotype in proneural BTICs and that the LAP isoform is responsible for this transdifferentiation. Independent of glioma subtype, LAP and LIP can elicit opposing effects. Nevertheless, both isoforms might contribute to tumor progression, since shifting the balance between LAP and LIP might add to BTICs capability to adapt to microenvironmental cues, e.g. by adopting a more migratory or proliferative phenotype. In contrast to the findings in breast CA, TGFβ acted independently of C/EBPβ isoforms. Ongoing experiments will provide further insight into downstream effector molecules and regulatory mechanisms for each isoform in GBM.
Echocardiography and lung ultrasonography for the assessment and management of acute heart failure
Authors: Susanna Price, Elke Platz, Louise Cullen, Guido Tavazzi, Michael Christ, Martin R. Cowie, Alan S. Maisel, Josep Masip, Oscar Miro, John J. McMurray, W. Frank Peacock, F. Javier Martin-Sanchez, Salvatore Di Somma, Hector Bueno, Uwe Zeymer, Christian Mueller
Journal: Nature Reviews Cardiology (2017)

The successful management of patients with acute heart failure (AHF) involves early diagnosis, rapid identification of underlying causes, and immediate implementation of effective therapies. In this Consensus Statement, the AHF Study Group of the ESC Acute Cardiovascular Care Association reviews the roles of echocardiography and lung ultrasonography in the assessment and management of patients with AHF. Echocardiography is increasingly recommended for the diagnosis and assessment of patients with severe cardiac disease, including acute heart failure. Although previously considered to be within the realm of cardiologists, the development of ultrasonography technology has led to the adoption of echocardiography by acute care clinicians across a range of specialties. Data from echocardiography and lung ultrasonography can be used to improve diagnostic accuracy, guide and monitor the response to interventions, and communicate important prognostic information in patients with acute heart failure. However, without the appropriate skills and a good understanding of ultrasonography, its wider application to the most acutely unwell patients can have substantial pitfalls. This Consensus Statement, prepared by the Acute Heart Failure Study Group of the ESC Acute Cardiovascular Care Association, reviews the existing and potential roles of echocardiography and lung ultrasonography in the assessment and management of patients with acute heart failure, highlighting the differences from established practice where relevant.
STUDIES ON FERMENT ACTION
Authors: James W. Jobling, Carroll G. Bull
Journal: The Journal of Experimental Medicine (1912)

1. Erythrocytes have definite lipoidal constituents and lipoidal combinations peculiar to the species. 2. Certain lipoids and lipoidal combinations act as specific antigens. 3. The increase in serum lipase which occurs upon immunization of animals to foreign red cells is, at least in part, specific. 4. This specific lipase plays, no doubt, an important part in specific serum hemolyses.
Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma
Authors: Jubayer A Hossain, Md A Latif, Lars A R Ystaas, Sandra Ninzima, Kristoffer Riecken, Arnaud Muller, Francisco Azuaje, Justin V Joseph, Krishna M Talasila, Jiwan Ghimire, Boris Fehse, Rolf Bjerkvig, Hrvoje Miletic
Journal: Neuro-Oncology (2019)

Abstract Background Suicide gene therapy for malignant gliomas has shown encouraging results in the latest clinical trials. However, prodrug application was most often restricted to short-term treatment (14 days), especially when replication-defective vectors were used. We previously showed that a substantial fraction of herpes simplex virus thymidine kinase (HSV-TK) transduced tumor cells survive ganciclovir (GCV) treatment in an orthotopic glioblastoma (GBM) xenograft model. Here we analyzed whether these TK+ tumor cells are still sensitive to prodrug treatment and whether prolonged prodrug treatment can enhance treatment efficacy. Methods Glioma cells positive for TK and green fluorescent protein (GFP) were sorted from xenograft tumors recurring after suicide gene therapy, and their sensitivity to GCV was tested in vitro. GBM xenografts were treated with HSV-TK/GCV, HSV-TK/valganciclovir (valGCV), or HSV-TK/valGCV + erlotinib. Tumor growth was analyzed by MRI, and survival as well as morphological and molecular changes were assessed. Results TK-GFP+ tumor cells from recurrent xenograft tumors retained sensitivity to GCV in vitro. Importantly, a prolonged period (3 mo) of prodrug administration with valganciclovir (valGCV) resulted in a significant survival advantage compared with short-term (3 wk) application of GCV. Recurrent tumors from the treatment groups were more invasive and less angiogenic compared with primary tumors and showed significant upregulation of epidermal growth factor receptor (EGFR) expression. However, double treatment with the EGFR inhibitor erlotinib did not increase therapeutic efficacy. Conclusion Long-term treatment with valGCV should be considered as a replacement for short-term treatment with GCV in clinical trials of HSV-TK mediated suicide gene therapy.
A Registry Study on Treatment of Patients with Acquired Protein C Deficiency with a Protein C Concentrate (Human)
Authors: Paul Knoebl, Michael Sasse, Maria Pia De Carolis, Jacqueline A Dyck-Jones, Sandra Ehrle, Maureen Finnerty, David Gelmont, Leman Yel, Mahmoud Loghman-Adham, Doris Fischer
Journal: Blood (2016)
Tandem Autologous Followed By Nonmyeloablative Allogeneic Transplantation in Relapsed High Risk Follicular Lymphoma Leads to Excellent Long Term Progression-Free Survival after 8 Years of Follow-up
Authors: Magalie Tardif, Imran Ahmad, Nadia M. Bambace, Lea Bernard, Lambert Busque, Jean-Sebastien Delisle, Thomas Kiss, Isabelle Fleury, Silvy Lachance, Luigina Mollica, Céline Nkoué, Denis-Claude Roy, Jean Roy, Sandra Cohen
Journal: Blood (2016)