tbuckley/cabot-search huggingface dataset:
Thermoresponsive Supramolecular Chemotherapy by “V”‐Shaped Armed β‐Cyclodextrin Star Polymer to Overcome Drug Resistance
Authors: Xiaoshan Fan, Hongwei Cheng, Xiaoyuan Wang, Enyi Ye, Xian Jun Loh, Yun‐Long Wu, Zibiao Li
Journal: Advanced Healthcare Materials (2017)

Abstract Pump mediated drug efflux is the key reason to result in the failure of chemotherapy. Herein, a novel star polymer β‐CD‐ v ‐(PEG‐β‐PNIPAAm) 7 consisting of a β‐CD core, grafted with thermo‐responsive poly( N ‐isopropylacrylamide) (PNIPAAm) and biocompatible poly(ethylene glycol) (PEG) in the multiple “V”‐shaped arms is designed and further fabricated into supramolecular nanocarriers for drug resistant cancer therapy. The star polymer could encapsulate chemotherapeutics between β‐cyclodextrin and anti‐cancer drug via inclusion complex (IC). Furthermore, the temperature induced chain association of PNIPAAm segments facilitated the IC to form supramolecular nanoparticles at 37 °C, whereas the presence of PEG impart great stability to the self‐assemblies. When incubated with MDR‐1 membrane pump regulated drug resistant tumor cells, much higher and faster cellular uptake of the supramolecular nanoparticles were detected, and the enhanced intracellular retention of drugs could lead to significant inhibition of cell growth. Further in vivo evaluation showed high therapeutic efficacy in suppressing drug resistant tumor growth without a significant impact on the normal functions of main organs. This work signifies thermo‐responsive supramolecular chemotherapy is promising in combating pump mediated drug resistance in both in vitro and in vivo models, which may be encouraging for the advanced drug delivery platform design to overcome drug resistant cancer.
18F-FDG-PET/CT for the Visualization of Inflammatory Component of Radiation-Induced Lung Injury After Stereotactic Radiotherapy
Authors: Olarn Roengvoraphoj, Montserrat Pazos-Escudero, Chukwuka Eze, Maurice Dantes, Farkhad Manapov
Journal: Clinical Nuclear Medicine (2017)

Visualization and metabolic analysis of acute inflammation in the lung parenchyma plays a crucial role for the prediction and diagnosis of radiation-induced lung injury and is particularly important in medically inoperable patients because of a priori very limited pulmonary function. This case confirms that a radiation-induced lung injury is accompanied by acute inflammatory reaction in the lung parenchyma irradiated with a total dose of 12-40 Gy. This well-defined inflammation component could be exactly characterized with FDG-PET/CT.
Abstract 13480: High Resolution MRI for Characterization of Inflammation within Abdominal Aortic Aneurysm
Authors: Chengcheng Zhu, Thomas A Hope, Henrik Haraldsson, Farshid Faraji, David Saloner, Michael Hope
Journal: Circulation (2016)

Background: Abdominal aortic aneurysms (AAAs) with focal inflammation have been reported to grow 3 times faster than those without. Ultrasmall superparamagnetic iron oxide (USPIO) particles can identify inflammation (macrophages) in vivo using MRI. USPIOs induce both T1 and T2* shortening. Previous studies used 2D T2* mapping methods, which had limited slice resolution (5mm). We aim to evaluate 3D higher resolution techniques for inflammation imaging. Hypothesis: 3D MRI can identify AAA inflammation with high resolution. Methods: Four MRI sequences were evaluated at 3T: traditional 2D T2* mapping (5mm slice); black blood fast-spin-echo (FSE) and ultra-short-TE (UTE) sequences with 1.3mm isotropic resolution, scan time 7 and 4 minutes; gradient echo (GRE) with 1.3x1.3x2.6mm 3 resolution in a breathhold (17s). Sequences were firstly tested in saline phantoms with USPIO concentrations 0.94mg Fe/L to 600mg Fe/L. 27 patients (all male, age 69±4.7, diameter 4.3±1.0cm) underwent MRI before and 2-3 days after USPIO injection. All patients had T2* and FSE scans. GRE and UTE were preliminary tested in 8 and 5 patients. Results: Phantom Study: UTE signal continually rises with increasing USPIO concentrations, whereas T2* values drop. Both FSE and GRE show signal increase-and-drop curves, however with different peaks (7.5 versus 60mg Fe/L). Patient study: In 27 patients, 10 patients were inflammation positive (T2* value decrease &gt;60%, Figure 1 ), and all showed FSE signal change: 3 drop, 3 increases, 4 both). GRE and UTE showed signal enhance ( Figure 1b ). 6 of them (60%) underwent intervention. Of the 17 negative patients, only 1 had intervention (p=0.004). Conclusion: 3D high resolution MRI can be used to identify USPIO uptake within AAA, with good agreement with traditional 2D T2* mapping method. AAA inflammation is related to progressive disease. These methods may help risk stratify patients with AAA disease by characterizing and quantifying inflammation.
Abstract 16861: Liposomal Prednisolone Aggravates Atherosclerosis by Promoting Lipotoxicity in Macrophages
Authors: Fleur van der Valk, Dominik Schulte, Menno de Winther, Esther Lutgens, Josbert Metselaar, Erik Stroes, Anouk Hamers
Journal: Circulation (2015)

Background: Whereas liposomal nanoparticles loaded with prednisolone phosphate (LN-PLP) reduced arterial wall inflammation in an atherosclerotic rabbit model, an unanticipated increase in arterial wall inflammation was observed in patients with atherosclerosis following LN-PLP infusions, despite proof of local accumulation in plaque macrophages. We hypothesized that this apparent discrepancy relates to the lipid-rich environment, and aimed to unravel the effect of LN-PLP upon local accumulation in lipid-laden macrophages. Methods &amp; Results: LN-PLP administration for two weeks (10mg/kg biweekly) in LDLR-/- mice on a high fat diet (n=15/group) resulted in increased influx of CD11b+ monocytes (11±6%) in the plaque, compared to empty LN and PBS (&lt;6%, p&lt;0.01), assessed with flow cytometry. Monocyte staining (ER-MP58) was also increased in the plaque (24±11%) after LN-PLP, whereas monocyte number in plasma decreased. After six weeks of LN-PLP administration, plaque stages progressed more rapidly (40% of plaques in stage V) in LDLR-/- mice (n=15/group) compared to free PLP, empty LN and PBS (for all &lt;10% of plaques in stage V). Immunohistochemical staining showed an increased macrophage content after LN-PLP (25±13% positivity for MAC3) compared to free PLP, empty LN or PBS (14%, p&lt;0.01). Necrotic core area was also higher after LN-PLP (68±4%) compared to free PLP, empty LN and PBS (&lt;50±3%, p2.00%, p&lt;0.01), (ii) increased expression of ER stress (e.g. PERK 2.5±0.2 after LN-PLP versus &lt;0.7±0.01 after empty LN or control, p&lt;0.05), and (iii) 23% of macrophages underwent apoptosis compared to &lt;3% of the macrophages in control conditions. Conclusion: Prednisolone, delivered locally in lipid-rich plaque macrophages, elicits a pro-atherogenic, lipotoxic effect, leading to more unstable plaques with larger necrotic core area and augmented macrophage apoptosis. These data bear direct consequences for future drug candidates aiming to target plaque macrophages; these require multifaceted screening taking the lipid-rich atherosclerotic milieu into account.
Primary Cancer vs Competing Causes of Death in Survivors of Head and Neck Cancer
Authors: Matthew C. Simpson, Sean T. Massa, Eric Adjei Boakye, Jastin L. Antisdel, Katherine A. Stamatakis, Mark A. Varvares, Nosayaba Osazuwa-Peters
Journal: JAMA Oncology (2017)

fornia Association of Health Plans opposed this bill, asserting that by releasing panelists' names they would be subject to lobbying
Infectious complications associated with the use of immune checkpoint inhibitors in oncology: reactivation of tuberculosis after anti PD-1 treatment
Authors: H. Picchi, C. Mateus, C. Chouaid, B. Besse, A. Marabelle, J.M. Michot, S. Champiat, A.L. Voisin, O. Lambotte
Journal: Clinical Microbiology and Infection (2017)
Extended-Duration Betrixaban Reduces the Risk of Rehospitalization Associated With Venous Thromboembolism Among Acutely Ill Hospitalized Medical Patients
Authors: Gerald Chi, Megan K. Yee, Alpesh N. Amin, Samuel Z. Goldhaber, Adrian F. Hernandez, Russell D. Hull, Alexander T. Cohen, Robert A. Harrington, C. Michael Gibson
Journal: Circulation (2017)
Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration
Authors: Bjoern O. Schroeder, George M.H. Birchenough, Marcus Ståhlman, Liisa Arike, Malin E.V. Johansson, Gunnar C. Hansson, Fredrik Bäckhed
Journal: Cell Host & Microbe (2017)
Abstract 16548: The Association of Mature Proprotein Convertase Subtilisin/Kexin Type 9 With Atherosclerotic Coronary Artery Disease in Patients With Familial Hypercholesteremia
Authors: Kazuhiro Nakao, Yu Kataoka, Teruo Noguchi, Hiroaki Hattori, Masatsune Ogura, Satohi Yasuda, Mariko Harada-Shiba
Journal: Circulation (2016)

Background:  Familial hypercholesterolemia (FH) increases a risk of premature atherosclerotic coronary artery disease (CAD). Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to LDL metabolism in FH, has been shown to promote atherosclerosis. While PCSK9 circulates as two subtypes: mature and furin-cleaved forms, their atherogenic effects remain to be elucidated. We analyzed the relationship of PCSK9 subtypes with atherosclerotic CAD in FH cases.   Method:  Serum mature and furin-cleaved PCSK9 levels were measured in 137 FH subjects receiving a statin by commercially available ELISA (BML.Inc, Tokyo, Japan). CAD was defined as the presence of significant coronary artery stenosis requiring revascularization. The association of mature and furin-cleaved PCSK9 with prevalence of CAD were analyzed, respectively.   Results:  Under lipid lowering therapies (high-intensity statin=52%, ezetimibe=22%), LDL-C, median mature and furin-cleaved PCSK9 levels were 128±36 mg/dl, 287 and 53 ng/ml, respectively. Mature PCSK9 was correlated with triglycerides (r=0.20, p=0.02). Furthermore, an elevated mature PCSK9 level was significantly associated with a higher prevalence of CAD [odds ratio (OR) for an increase per standard deviation=1.47, 95%CI 1.02-2.13, p=0.03]. By contrast, there were no significant relationships between furin-cleaved PCSK9 and prevalence of CAD. The association of mature PCSK9 with CAD was further analyzed by using its tertile (Figure). On multivariate analysis, mature PCSK9 level >383 ng/ml (=upper tertile) was an independent predictor for the presence of CAD [lower v. upper tertile: OR=3.92, 95%CI 1.33-11.6, p=0.01, lower v. mid tertile: OR=1.18, 95%CI 0.38-3.65, p=0.78].   Conclusion:  Higher prevalence of atherosclerotic CAD was observed in association with mature PCSK9 level. Our findings indicate mature PCSK9 as a potential risk marker to identify high-risk FH subjects harboring atherosclerotic CAD.
Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group
Authors: Brian M Alexander, Paul D Brown, Manmeet S Ahluwalia, Hidefumi Aoyama, Brigitta G Baumert, Susan M Chang, Laurie E Gaspar, Steven N Kalkanis, David R Macdonald, Minesh P Mehta, Riccardo Soffietti, John H Suh, Martin J van den Bent, Michael A Vogelbaum, Jeffrey S Wefel, Eudocia Q Lee, Patrick Y Wen
Journal: The Lancet Oncology (2017)
Scleroderma fibroblasts suppress angiogenesis via TGF-β/caveolin-1 dependent secretion of pigment epithelium-derived factor
Authors: Vasiliki Liakouli, Jacobo Elies, Yasser Mohamed El-Sherbiny, Margherita Scarcia, Gary Grant, Giuseppina Abignano, Emma C Derrett-Smith, Filomena Esteves, Paola Cipriani, Paul Emery, Christopher P Denton, Roberto Giacomelli, Georgia Mavria, Francesco Del Galdo
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Systemic sclerosis (SSc) is characterised by tissue fibrosis and vasculopathy with defective angiogenesis. Transforming growth factor beta (TGF-β) plays a major role in tissue fibrosis, including downregulation of caveolin-1 (Cav-1); however, its role in defective angiogenesis is less clear. Pigment epithelium-derived factor (PEDF), a major antiangiogenic factor, is abundantly secreted by SSc fibroblasts. Here, we investigated the effect of TGF-β and Cav-1 on PEDF expression and the role of PEDF in the ability of SSc fibroblasts to modulate angiogenesis. Methods PEDF and Cav-1 expression in fibroblasts and endothelial cells were evaluated by means of immunohistochemistry on human and mouse skin biopsies. PEDF and Cav-1 were silenced in cultured SSc and control fibroblasts using lentiviral short-hairpin RNAs. Organotypic fibroblast–endothelial cell co-cultures and matrigel assays were employed to assess angiogenesis. Results PEDF is highly expressed in myofibroblasts and reticular fibroblasts with low Cav-1 expression in SSc skin biopsies, and it is induced by TGF-β in vitro. SSc fibroblasts suppress angiogenesis in an organotypic model. This model is reproduced by silencing Cav-1 in normal dermal fibroblasts. Conversely, silencing PEDF in SSc fibroblasts rescues their antiangiogenic phenotype. Consistently, transgenic mice with TGF-β receptor hyperactivation show lower Cav-1 and higher PEDF expression levels in skin biopsies accompanied by reduced blood vessel density. Conclusions Our data reveal a new pathway by which TGF-β suppresses angiogenesis in SSc, through decreased fibroblast Cav-1 expression and subsequent PEDF secretion. This pathway may present a promising target for new therapeutic interventions in SSc.
La Región Europea de la OMS ha sido declarada libre de polio
Authors: M. S. Vilayleck
Journal: Eurosurveillance (2002)

La Region Europea de la OMS* fue oficialmente declarada libre de poliomielitis en la reunion celebrada en Copenhague, Dinamarca, el 21 de junio de 2002. Esta informacion fue publicada por la Comision Nacional Europea para la Certificacion de la Erradicacion de la Poliomielitis.
Human Tumor Stem-Cell Assay
Journal: New England Journal of Medicine (1983)

Author(s): Salmon, SE; Alberts, DS; Meyskens, FL; Moon, TE; Aapro, MS; Eliason, JR; Umbach, GE; Spitzer, G; Hug, V; Atkinson, EN; Plasse, TF; Weisenthal, LM; Balk, S; Selby, P; Buick, R; Tannock, I | Abstract: To the Editor: Since our group first reported on the potential clinical applications of the human tumor stem-cell, or clonogenic, assay in the Journal,1 we think some comment from us is warranted regarding the recent article by Selby et al.2 and the editorial by Von Hoff.3 We clearly agree that it is important to plate good single-cell suspensions, that drug-sensitivity criteria are still in the developmental stages,4 that some drugs may require the evaluation of various exposure times, that inappropriate drug concentrations may be misleading, that drugs requiring bioactivation present special problems, that radiation-survival curves with plateaus at. © 1983, Massachusetts Medical Society. All rights reserved.
The feasibility of an encapsulated cell approach in an animal deafness model
Authors: Anette Fransson, Jens Tornøe, Lars U. Wahlberg, Mats Ulfendahl
Journal: Journal of Controlled Release (2017)

For patients with profound hearing loss a cochlear implant (CI) is the only treatment today. The function of a CI depends in part of the function and survival of the remaining spiral ganglion neurons (SGN). It is well known from animal models that inner ear infusion of neurotrophic factors prevents SGN degeneration and maintains electrical responsiveness in deafened animals. The purpose with this study was to investigate the effects of a novel encapsulated cell (EC) device releasing neurotrophic factors in the deafened guinea pig. The results showed that an EC device releasing glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) implanted for four weeks in deafened guinea pigs significantly preserved the SGNs and maintained their electrical responsiveness. There was a significant difference between BDNF and GDNF in favour of GDNF. This study, demonstrating positive structural and functional effects in the deafened inner ear, suggests that an implanted EC device releasing biologically protective substances offers a feasible approach for treating progressive hearing impairment.
Abstract 1005: Rac1 Deletion Impairs Ischemic Preconditioning In Mouse Hearts
Authors: Zheqing P Cai, Zhenyun Shen, Lewis C Becker
Journal: Circulation (2007)

The small GTPase Rac1 plays an important role in activation of NADPH oxidase, the major source of reactive oxygen species (ROS) in the heart following ischemia-reperfusion. The production of ROS is thought to be required for the induction of ischemic preconditioning (IPC). In this study, we examined whether Rac1 itself is essential for IPC cardioprotection. Temporally regulated cardiac-specific Rac1 deficient mice were generated by crossing Rac1 loxP/loxP  mice with MHC-MerCreMer +/+  mice, expressing a tamoxifen-inducible Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding domains (MerCreMer) under the control of the α-myosin heavy chain (MHC) promoter. Rac1 deletion was induced by intra-peritoneal injection of tamoxifen in the experimental mice (Rac1 loxP/+ ;MHC-MerCreMer +/−  ) and confirmed by Western blot analysis. Littermates with the same genotype were treated with vehicle as controls. No change in Rac1 levels occurred in the control mice. Wildtype mice were subjected to 30 min of ischemia (I-30) and 120 min of reperfusion (R-120) with or without IPC, which consisted of I-10/R-5. The conditional Rac1 deficient mice and their littermate controls were exposed to I-30/R-120 after IPC. IPC significantly reduced infarct size (IS) in the wildtype mouse hearts, expressed as a percent of the area at risk (RA) (IS/RA: no IPC/IPC = 46.0 ± 2.7/16.7 ± 3.8, p
Stromal PD-L1–Positive Regulatory T cells and PD-1–Positive CD8-Positive T cells Define the Response of Different Subsets of Non–Small Cell Lung Cancer to PD-1/PD-L1 Blockade Immunotherapy
Authors: Si-Pei Wu, Ri-Qiang Liao, Hai-Yan Tu, Wen-Jun Wang, Zhong-Yi Dong, Shu-Mei Huang, Wei-Bang Guo, Lan-Ying Gou, Hui-Wen Sun, Qi Zhang, Zhi Xie, Li-Xu Yan, Jian Su, Jin-Ji Yang, Wen-Zhao Zhong, Xu-Chao Zhang, Yi-Long Wu
Journal: Journal of Thoracic Oncology (2017)
Réponse aux lettres : Epidémies de parvovirus B19
Authors: G Gonçalves, A M Correia, P Palminha, Helena Rebelo-Andrade, A Alves
Journal: Eurosurveillance (2005)

We are grateful for the comments provided by Kelly and Leydon, and Bernard J Cohen. They seem to share our previously expressed opinion that ’in the context of measles and rubella elimination programs, study protocols should include data collection proced
Anti–sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia
Authors: Bradley Wallace, Amelie Peisl, Gregory Seedorf, Taylor Nowlin, Christina Kim, Jennifer Bosco, Jon Kenniston, Dennis Keefe, Steven H. Abman
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Pregnancies complicated by antenatal stress, including preeclampsia (PE) and chorioamnionitis (CA), increase the risk for bronchopulmonary dysplasia (BPD) in preterm infants, but biologic mechanisms linking prenatal factors with BPD are uncertain. Levels of sFlt-1 (soluble fms-like tyrosine kinase 1), an endogenous antagonist to VEGF (vascular endothelial growth factor), are increased in amniotic fluid and maternal blood in PE and associated with CA.Because impaired VEGF signaling has been implicated in the pathogenesis of BPD, we hypothesized that fetal exposure to sFlt-1 decreases lung growth and causes abnormal lung structure and pulmonary hypertension during infancy.To test this hypothesis, we studied the effects of anti-sFlt-1 monoclonal antibody (mAb) treatment on lung growth in two established antenatal models of BPD that mimic PE and CA induced by intraamniotic (i.a.) injections of sFlt-1 or endotoxin, respectively. In experimental PE, mAb was administered by three different approaches, including antenatal treatment by either i.a. instillation or maternal uterine artery infusion, or by postnatal intraperitoneal injections.With each strategy, mAb therapy improved infant lung structure as assessed by radial alveolar count, vessel density, right ventricular hypertrophy, and lung function. As found in the PE model, the adverse lung effects of i.a. endotoxin were also reduced by antenatal or postnatal mAb therapy.We conclude that treatment with anti-sFlt-1 mAb preserves lung structure and function and prevents right ventricular hypertrophy in two rat models of BPD of antenatal stress and speculate that early mAb therapy may provide a novel strategy for the prevention of BPD.
The Autologous Serum Skin Test as a Prognostic Factor for the Severity and Duration of Chronic Urticaria after five years of Follow-up
Authors: Karen Milena Lozano Mosquera, Beatriz Moya Camacho, Ruth Mielgo Ballesteros, Alicia Enriquez Matas, Miguel Angel Díaz, Consuelo Fernández Rodríguez, Lys Herraez
Journal: Journal of Allergy and Clinical Immunology (2018)
Recent Improvements In Survival In Light Chain Amyloidosis and the Importance of An Early Mortality Risk Score
Authors: Shaji Kumar, Morie Gertz, Martha Lacy, David Dingli, Suzanne R. Hayman, Francis Buadi, Kristen Detweiler-Short, Steven Zeldenrust, Nelson Leung, Philip R. Greipp, John Lust, Stephen Russell, Robert Kyle, Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2010)
Ventriculoperitoneal-Shunt Placement for Normal-Pressure Hydrocephalus
Authors: Mahmoud A AbdelRazek, Nagagopal Venna
Journal: New England Journal of Medicine (2017)

A 70-year-old woman presented with a 2-year history of gait disturbance, urinary incontinence, and cognitive impairment and had radiologic findings of normal-pressure hydrocephalus. After placement of a ventriculoperitoneal shunt, her condition improved substantially.
Review: In patients with a first VTE, extended testing for undiagnosed cancer does not reduce mortality
Authors: Alexander Gallus
Journal: Annals of Internal Medicine (2017)

Source Citation Robertson L, Yeoh SE, Stansby G, Agarwal R. Effect of testing for cancer on cancer- and venous thromboembolism (VTE)-related mortality and morbidity in people with unprovoked VTE. Cochrane Database Syst Rev. 2017;8:CD010837. 28832905