tbuckley/cabot-search huggingface dataset:
Immunological differences between insect venom‐allergic patients with and without immunotherapy and asymptomatically sensitized subjects
Authors: L. Arzt, D. Bokanovic, C. Schrautzer, K. Laipold, C. Möbs, W. Pfützner, S. A. Herzog, J. Vollmann, N. Reider, B. Bohle, W. Aberer, G. J. Sturm
Journal: Allergy (2017)

Abstract Background Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy ( VIT ) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings. Methods We included 77 asymptomatically sensitized subjects, 85 allergic patients with acute systemic sting reactions, and 61 allergic patients currently treated with VIT . Levels of sIgE and sIgG 4 to bee and vespid venom, rA pi m 1, and rV es v 5 were measured immediately after allergic sting reactions or before sting challenges and 4 weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT inhibition and ELIFAB assay. Results Median sIgG 4 levels were 96‐fold higher in VIT patients ( P &lt; .001) while sIgE / sIgG 4 ratios were consistently lower ( P &lt; .001). The ELIFAB assay was paralleled by low sIgE / sIgG 4 ratios in VIT patients, showing markedly higher allergen‐blocking capacity ( P &lt; .001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG 4 levels were increased in allergic and asymptomatically sensitized patients, but not in VIT patients. Conclusion Immunological responses after stings varied in bee and vespid venom‐allergic patients. In patients under VIT , sIgE and sIgG 4 remained completely stable after sting challenges. Monitoring VIT efficacy was only possible in vespid venom allergy, and the sIgG 4 threshold for rV es v 5 had the highest sensitivity to confirm tolerance. The BAT inhibition test was the most reliable tool to confirm tolerance on an individual basis.
Application of prognostic scores in the STOPAH trial: Discriminant function is no longer the optimal scoring system in alcoholic hepatitis
Authors: Ewan H. Forrest, Stephen R. Atkinson, Paul Richardson, Steven Masson, Stephen Ryder, Mark R. Thursz, Michael Allison, Anne McCune, Dermot Gleeson, Andrew Austin, David Patch, Ashwin Dhanda, Debbie Shawcross, Mark Wright
Journal: Journal of Hepatology (2017)
Core outcome sets in dermatology: report from the second meeting of the International Cochrane Skin Group Core Outcome Set Initiative
Authors: J. Kottner, L. Jacobi, E. Hahnel, M. Alam, K. Balzer, D. Beeckman, C. Busard, J. Chalmers, S. Deckert, V. Eleftheriadou, K. Furlan, S.E.R. Horbach, J. Kirkham, A. Nast, P. Spuls, D. Thiboutot, L. Thorlacius, K. Weller, H.C. Williams, J. Schmitt
Journal: British Journal of Dermatology (2018)

Summary Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG-COUSIN) supports the development of core outcomes in dermatology. In the second CSG-COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers.
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease
Authors: Yang Bai, Miao Li, Yanmei Zhou, Lei Ma, Qian Qiao, Wanling Hu, Wei Li, Zachary Patrick Wills, Wen-Biao Gan
Journal: Molecular Neurodegeneration (2017)

Alzheimer's disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD.We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice. We also performed calcium imaging to determine the effect of Aβ oligomers on dendritic calcium activity. In addition, structural and functional two-photon imaging were used to examine the link between abnormal dendritic calcium activity and changes in dendritic spine size in the AD mouse model.We found that somatic calcium activities of layer 2/3 neurons were significantly lower in the primary motor cortex of 3-month-old APPswe/PS1dE9 mice than in wild type mice during quiet resting, but not during running on a treadmill. Notably, a significantly larger fraction of apical dendrites of layer 2/3 pyramidal neurons showed calcium transients with abnormally long duration and high peak amplitudes during treadmill running in AD mice. Administration of Aβ oligomers into the brain of wild type mice also induced abnormal dendritic calcium transients during running. Furthermore, we found that the activity and size of dendritic spines were significantly reduced on dendritic branches with abnormally prolonged dendritic calcium transients in AD mice.Our findings show that abnormal dendritic calcium transients and synaptic depotentiation occur before amyloid plaque formation in the motor cortex of the APPswe/PS1dE9 mouse model of AD. Dendritic calcium transients with abnormally long durations and high amplitudes could be induced by soluble Aβ oligomers and contribute to synaptic deficits in the early pathogenesis of AD.
AC-93253 iodide, a novel Src inhibitor, suppresses NSCLC progression by modulating multiple Src-related signaling pathways
Authors: Yi-Hua Lai, Sih-Yin Lin, Yu-Shan Wu, Huei-Wen Chen, Jeremy J. W. Chen
Journal: Journal of Hematology & Oncology (2017)

The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds.Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment. Src and Src-related protein expression in AC-93253 iodide-treated PC9, PC9/gef, and A549 cells were assessed by western blotting. The effects of AC-93253 iodide on cancer cell colony formation, invasion, and migration were assessed in PC9 and PC9/gef cells. The synergistic effects of gefitinib and AC-93253 iodide were evaluated by combination index (CI)-isobologram analysis in gefitinib-resistant cell lines. The efficacy of AC-93253 iodide in vivo was determined using nude mice treated with either the compound or the vehicle.Among the compounds, AC-93253 iodide exhibited the most potent dose-independent inhibitory effects on the activity of Src as well as on that of the Src-related proteins EGFR, STAT3, and FAK. Furthermore, AC-93253 iodide significantly suppressed cancer cell proliferation, colony formation, invasion, and migration in vitro and tumor growth in vivo. AC-93253 iodide sensitized tumor cells to gefitinib treatment regardless of whether the cells were gefitinib-sensitive (PC9) or resistant (H1975 and PC9/gef), indicating that it may exert synergistic effects when used in combination with established therapeutic agents. Our findings also suggested that the inhibitory effects of AC-93253 iodide on lung cancer progression may be attributable to its ability to modulate multiple proteins, including Src, PI3K, JNK, Paxillin, p130cas, MEK, ERK, and EGFR.Our data suggest that AC-93253 iodide inhibits NSCLC cell growth and motility by regulating multiple Src-related pathways. Our findings may facilitate the development of therapeutic strategies and anti-tumor drugs that may be useful for treating lung cancer in the future.
Recent Advances in the Application of Vitamin E TPGS for Drug Delivery
Authors: Conglian Yang, Tingting Wu, Yan Qi, Zhiping Zhang
Journal: Theranostics (2017)

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems.The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity.Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor.In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations.These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors.It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future.
Concordance study between IBM Watson for Oncology (WFO) and clinical practice for breast and lung cancer patients in China
Authors: X.C. Zhang, N. Zhou, C.T. Zhang, H.Y. Lv, T.J. Li, J.J. Zhu, M. Jiang, H.L. Hou, D. Liu, A.Q. Li, G. Liu, G.Q. Zhang
Journal: Annals of Oncology (2017)
PTH-050 Robot magnet-controlled upper gi capsule endoscopy using the ankon navicam® system: first reported experience outside china
Authors: H-L Ching, MF Hale, R Sidhu, ME McAlindon
Journal: Gut (2017)

Introduction  Gastroscopy (OGD) is invasive and not always well tolerated. Capsule endoscopy of the upper GI tract might be possible if effective control allowed movement to all areas of the stomach which, unlike the small bowel, is capacious and irregular in shape. The NaviCam® (Ankon Technologies Co, Ltd Wuhan, Shanghai, China) contains magnetic material and can be controlled by an external robot magnet, the polarity and proximity of which can be manipulated using joysticks. Two frames per second allow real-time visualisation. A Chinese multicentre study has shown a high sensitivity and specificity for detecting focal gastric lesions when compared to OGD (1). In this study, imaging quality and patient tolerance of upper GI examination using the robot magnet-controlled NaviCam® was assessed.  Method  Patients with symptoms of dyspepsia swallowed 100mls of water containing 10mls simethicone 15 min prior to 1L of water followed by the NaviCam®. Both clarity of gastric views and adequacy of gastric distension were assessed (1, poor; 2, reasonable; 3, good), as was completeness of views of all areas of the gastric mucosa (1,>75% obscured; 2,>50% obscured; 3,  Results  The mean age of the eight participants was 47.1±20.4 (75% male). The NaviCam® could be held stationary in the presence of peristaltic waves and could be moved proximally using a preset magnetic programme activated by a ‘shoot’ button on the joystick which caused the capsule to cartwheel proximally over the rugal folds to a chosen proximal location. Mean duration of examination was 25±7 mins. Mean clarity and distension scores of 2.5±0.5 and 2.9±0.3 were achieved. Completeness of view was 5±0 for the gastric cardia, fundus, greater and lesser curvature, anterior and posterior wall, antrum and pylorus. Few oesophageal images were obtained and duodenal images were not assessed during the live examination (but are provided following passage of the capsule through the pylorus). Three examinations were normal. Gastritis and cystic fundic gland polyps were ?diagnosed in 2 and 3 cases respectively. Anxiety, discomfort and pain scores (worst-best=0–10) were 1±0, 1.3±0.6, and 1±0 respectively.  Conclusion  The NaviCam® demonstrates excellent control and gastric views and is extremely well tolerated. Greater frame acquisition rate is likely to improve oesophageal visualisation.  Reference  . Liao Z, Hou X, Lin-Hu EQ, Sheng JQ, Ge ZZ, Jiang B, et al. Accuracy of Magnetically Controlled Capsule Endoscopy, Compared With Conventional Gastroscopy, in Detection of Gastric Diseases. Clin Gastroenterol Hepatol. 2016;14(9):1266–73.e1.  Disclosure of Interest  H.-L. Ching Conflict with: Ankon, Conflict with: Travel expenses to capsule conference from Ankon., M Hale: None Declared, R Sidhu: None Declared, M McAlindon Conflict with: Ankon, Conflict with: Travel expenses to capsule conference from Ankon.
Evolutionary approaches to deprivation transform the ethics of policy making
Authors: Coralie Chevallier
Journal: Behavioral and Brain Sciences (2017)

Abstract When designing public policies, decision makers often rely on their own behavioral preferences. Pepper &amp; Nettle's (P&amp;N's) theory suggests that these preferences are unlikely to be appropriate when applied to a different environment (e.g., a low-income environment with fewer career opportunities). This theory has profound implications for the design and ethics of public policies.
Black-white differences in serum antioxidant concentrations reflect differences in food intake:: the Coronary Artery Risk Development in Young Adults (CARDIA) study
Authors: E. Guallar, F. J. vier Jimenez, Van apos, P. t Veer, P. Bode, J. M. Martin Moreno, F. J. Kok
Journal: Circulation (2001)

P79     Blacks have been reported to have lower serum antioxidant  vitamin concentrations than whites. We studied black-white patterns of  antioxidant concentrations and food intake in 1985-86 (3477 nonusers of  supplemental vitamins A, C, and E, 18-30 year old). Black men and women  had lower levels than white men and women of serum alpha-tocopherol  (aTOCO), alpha-carotene (aCARO) and beta-carotene (bCARO), but higher  levels of gamma tocopherol (gTOCO) and similar levels of lycopene  (LYCO), adjusted for age, plasma lipids, clinic, and smoking. Intake of  minimally processed plant foods (MPPF: whole grain, fruits, vegetables,  nuts, and Table legumes processed to preserve nutrient content) was  positively correlated with aTOCO, aCARO, and bCARO. Further adjustment  for this and related food groups reduced differences in serum  antioxidant concentrations between black and white women: aTOCO  (0.09vs0.06), gTOCO (.022vs.011), aCARO (2.22vs1.42) and bCARO  (3.96vs1.16), all still significant except gTOCO, with a similar  pattern of reductions for men. Thus, low serum antioxidants, indicators  of cardiovascular disease risk in blacks, reflect differences in food  intake between blacks and whites. Culturally-specific dietary  interventions may be necessary for an improvement in antioxidant status  to reduce the risk of developing cardiovascular  disease.
Evaluation of NGS and RT-PCR Methods for ALK Rearrangement in European NSCLC Patients: Results from the European Thoracic Oncology Platform Lungscape Project
Authors: Igor Letovanec, Stephen Finn, Panagiota Zygoura, Paul Smyth, Alex Soltermann, Lukas Bubendorf, Ernst-Jan Speel, Antonio Marchetti, Daisuke Nonaka, Kim Monkhorst, Henrik Hager, Miguel Martorell, Aleksandra Sejda, Richard Cheney, Javier Hernandez-Losa, Eric Verbeken, Walter Weder, Spasenija Savic, Alessia Di Lorito, Atilio Navarro, Enriqueta Felip, Arne Warth, Paul Baas, Peter Meldgaard, Fiona Blackhall, Anne-Marie Dingemans, Hendrik Dienemann, Rafal Dziadziuszko, Johan Vansteenkiste, Cathal O'Brien, Thomas Geiger, Jon Sherlock, Jeoffrey Schageman, Urania Dafni, Roswitha Kammler, Keith Kerr, Erik Thunnissen, Rolf Stahel, Solange Peters, Rolf A. Stahel, Rafael Rosell, Fiona Blackhall, Urania Dafni, Keith M. Kerr, Miguel Ángel Molina, Lukas Bubendorf, Walter Weder, Erik Thunnissen, Solange Peters, Stephen Finn, Anita Hiltbrunner, Roswitha Kammler, Thomas Geiger, Nesa Marti, Urania Dafni, Zoi Tsourti, Varvara Polydoropoulou, Panagiota Zygoura, Stephen Finn, Paul Smyth, Cathal O’Brien, Steven Gray, Walter Weder, Alex Soltermann, Isabelle Opitz, Alessandra Curioni, Lukas Bubendorf, Spasenija Savic, Didier Lardinois, Anne-Marie Dingemans, Ernst-Jan M. Speel, Andrea Ruland, Antonio Marchetti, Alessia Di Lorito, Graziano De Luca, Sara Malatesta, Fiona Blackhall, Daisuke Nonaka, Anne Marie Quinn, Lynsey Franklin, Wojciech Biernat, Ania Wrona, Witold Rzyman, Jacek Jassem, Peter Meldgaard, Henrik Hager, Line B. Madsen, Carlos Camps, Miguel Martorell, Eloisa Jantus-Lewintre, Ricardo Guijarro, Keith M. Kerr, Marianne Nicolson, David A.J. Stevenson, William Mathieson, Paul Baas, Jeroen de Jong, Kim Monkhorst, Erik Thunnissen, Egbert Smit, Coralien van Setten, Joop de Langen, Enriqueta Felip, Javier Hernandez-Losa, Irene Sansano, Richard Cheney, Mary Beth Pine, Mary Reid, Elizabeth Taylor, Kristiaan Nackaerts, Christophe Dooms, Els Wauters, Sara Van Der Borght, Hendrik Dienemann, Thomas Muley, Arne Warth
Journal: Journal of Thoracic Oncology (2017)
Abstract 17153: Smooth Muscle Cells Regulate the Capacity for Endothelial Regeneration by Coordinating Notch1 Mediated Metabolism, Histone Acetylation and Gene Regulation in a BMPR2 Dependent Manner
Authors: Kazuya Miyagawa, Jan K Hennigs, Caiyun G Li, Pin-I Chen, Mouer Wang, Shalina Taylor, Silin Sa, Aiqin Cao, Lingli Wang, Marlene Rabinovitch
Journal: Circulation (2016)

Maintaining endothelial cells (EC) as a monolayer in the vessel wall, depends on a profile of gene expression and on the metabolic state, features influenced by contact with cells such as pericytes and smooth muscle cells (SMC). Dysregulation of BMP receptor 2 (BMPR2) signaling disrupts pulmonary artery (PA) EC metabolism and monolayer formation and is associated with vascular diseases such as pulmonary arterial hypertension. Here we show that BMPR2 signaling in either EC or SMC is required to maintain contact-dependent production of collagen IV, triggering integrin linked kinase to target p-JNK to caveolin1, and activate γ-secretase. Notch1 activation by the γ-secretase produces the Notch1 intracellular domain (N1ICD) that is responsible for increasing glycolysis, mitochondrial mass, and oxidative phosphorylation in association with an increase in the enzyme, 6-phosphofructo-2-kinase (PFKFB3). The increase in PFKFB3 is responsible for elevated levels of the mitochondrial citrate transporter that generates acetyl CoA and for heightened acetylation of histones H3K27 and H3K9. The latter are associated with the transcription of N1ICD target genes Hey1, HES1 and c-Myc, and for the Hey1/HES1 mediated repression of migratory genes Neuropilin1 and 2. This maintains the Notch1-dependent ‘stalk cell’ phenotype that retains the capacity to proliferate but not migrate. As a result there is rapid re-endothelialization of the PAEC monolayer in a scratch wound healing assay that is impaired with loss of BMPR2 in both PAEC and PASMC in contact co-cultures. Consistent with this, a mouse heterozygous knockout for BMPR2 has impaired re-endothelialization following wire injury of the carotid artery and neointimal formation is greatly enhanced. Taken together our data provide novel evidence for the role of BMPR2 in EC and SMC myoendothelial junctions in maintaining the proliferative capacity of EC in response to injury and thereby in limiting occlusive changes (Figure A and B).
Minimal residual disease by either flow cytometry or cytogenetics prior to an allogeneic hematopoietic stem cell transplant is associated with poor outcome in acute myeloid leukemia
Authors: Maxim Norkin, Lakshmikanth Katragadda, Fei Zou, Sican Xiong, Myron Chang, Yunfeng Dai, Jack W. Hsu, Jan S. Moreb, Helen Leather, Hemant S. Murthy, Nosha Farhadfar, Ying Li, Robert Hromas, Randy A. Brown, Christopher R. Cogle, John R. Wingard
Journal: Blood Cancer Journal (2017)

Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC), conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are routinely performed on bone marrow specimens prior to HCT to assess disease status. We questioned the extent by which pre-HCT evidence of minimal residual disease (MRD) detected by these standard assays, corresponded with post-HCT relapse. We conducted a single center, retrospective study of 166 AML patients who underwent HCT. Thirty-eight of one hundred sixty-six (23%) patients in complete remission (CR) or CR with incomplete count recovery (CRi) had MRD detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had significantly longer overall survival (OS) and relapse-free survival than patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In patients with MRDpos prior to HCT, the presence of acute graft vs. host disease (GVHD) (grade ≥ 2) or chronic GVHD significantly improved progression free survival (PFS) (hazard ratio (HR) = 0.053 (95% confidence interval (CI): 0.01-0.279), P = 0.0005) and OS (HR = 0.211 (95% CI: 0.081-0.547), P = 0.0014).
A rs4374383 Single Nucleotide Polymorphisms of MERTK gene is linked to a higher likelihood of hepatocellular carcinoma in patients with HCV cirrhosis
Authors: V. Di Marco, V. Calvaruso, S. Grimaudo, D. Ferraro, M. Bavetta, A. Di Cristina, G. Cabibbo, E. Conte, A. Craxi
Journal: Hepatology (2013)
Marcada disminución de la tos ferina a partir del restablecimiento de la vacunación contra la tos ferina en Suecia
Authors: P Olin, H O Hallander
Journal: Eurosurveillance (1999)

En enero de 1996, 17 anos despues de la retirada de la vacuna de celulas completas en 1979 (1), se introdujo la inmunizacion con vacuna acelular contra la tos ferina en el programa de vacunacion sueco, para ser administrada a ninos de 3, 5 y 12 meses. En pocos meses, la cobertura alcanzo al menos un 95%, principalmente con una vacuna contra la tos ferina de tres antigenos componentes asociada a la vacuna combinada contra la difteria y el tetanos (DTPa). En algunas regiones se administro una vacuna acelular contra la tos ferina de tres antigenos a preescolares mas mayores y en una region (Gotemburgo y alrededores) se puso en marcha una campana de barrido con una vacuna contra la tos ferina de un antigeno, como parte de un ensayo clinico (2).
Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons
Authors: Qiang Wang, Shu-Ling Chiu, Eleftheria Koropouli, Ingie Hong, Sarah Mitchell, Teresa P. Easwaran, Natalie R. Hamilton, Ahleah S. Gustina, Qianwen Zhu, David D. Ginty, Richard L. Huganir, Alex L. Kolodkin
Journal: Neuron (2017)