tbuckley/cabot-search huggingface dataset:
Anti-IL-6 treatment in two pediatric patients with severe persistent asthma with the IL4R 576 variant
Authors: Brittany Esty, Lisa M. Bartnikas, Louis M. Charbonnier, Amir Hossein Massoud, Carmen Leon-Astudillo, Gary Visner, Meera Subramaniam, Wanda Phipatanakul, Talal A. Chatila
Journal: Journal of Allergy and Clinical Immunology (2018)

The Interleukin-4 receptor alpha chain variant R576 (IL-4Ra-R576) is associated with severe asthma characterized by a mixed TH2-TH17 response. Past research demonstrated that treatment of Il4raR576 mice with anti-IL-6 antibody protected against severe airway inflammation. We analyzed the response of two patients with severe persistent asthma with the IL4RR576allelic variant treated with tocilizumab. Patient 1: 6-year-old with severe persistent, non-atopic asthma with homozygous IL4RR576 variant. He had ongoing severe exacerbations despite ICS/LABA, montelukast, prednisolone, azithromycin, theophylline, and IVIG. He started tocilizumab on 10/2016 at 10mg/kg/dose Q4wks then changed to 8mg/kg/dose Q2wks. Patient 2: 5-year-old with severe persistent, non-atopic asthma with heterozygous IL4RR576 variant. Patient had ongoing symptoms despite ICS/LABA, montelukast, and prednisolone. He had behavioral side effects with theophylline and lack of benefit with azithromycin. He started tocilizumab on 2/2017 at 10mg/kg/dose Q4wks then changed to 8mg/kg/dose Q2wks. Patient 1 had one hospital admission (ICU) after starting tocilizumab, a 66.7% reduction in admissions from year prior and 75% reduction from two years prior. FEV1 increased from 0.9L to 1.16L and C-ACT improved from 21 to 27. Patient 2 had one hospital admission after tocilizumab, a 50% reduction from year prior. FEV1 increased from 1.22L to 1.33L and was able to discontinue oral steroids. Flow cytometric analysis on patient 1 revealed increased circulating TH17 and TH2 cells at baseline that sharply declined following tocilizumab therapy, while those on patient 2 are currently pending. Tocilizumab may be an effective therapy for patients with severe persistent asthma associated with the IL4RR576 allelic variant.
Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study
Authors: Courtney D DiNardo, Keith W Pratz, Anthony Letai, Brian A Jonas, Andrew H Wei, Michael Thirman, Martha Arellano, Mark G Frattini, Hagop Kantarjian, Relja Popovic, Brenda Chyla, Tu Xu, Martin Dunbar, Suresh K Agarwal, Rod Humerickhouse, Mack Mabry, Jalaja Potluri, Marina Konopleva, Daniel A Pollyea
Journal: The Lancet Oncology (2018)
Trump administration allows states to deny Medicaid to unemployed people
Authors: Owen Dyer
Journal: BMJ (2018)

Under new guidance from the Trump administration, US states will be able to deny coverage by Medicaid—the publicly funded health insurance programme for US residents living near the poverty line—to able bodied adults who are not working or seeking employment.

Within hours of the guidance being issued,1 Kentucky became the first state to announce a new work requirement. The “community engagement and employment initiative” will be phased in during the second half of 2018, Matt Bevin, the state’s Republican governor, told a press conference. It will require able bodied Kentuckian adults to be in or seeking work or to be a student, volunteer, or caregiver, to qualify for Medicaid benefits.

Kentucky Medicaid recipients …
The Treatment of Bacterial Endocarditis with Penicillin
Authors: Manson Meads, H. William Harris, Maxwell Finland
Journal: New England Journal of Medicine (1945)

FLEMING,1 in his original studies on the antibacterial action of cultures of his strain of Penicillium, included some strains of Streptococcus viridans, which he found to vary considerably in their susceptibility. Others2 3 4 5 6 7 8 have since confirmed these findings with more purified preparations of penicillin in vitro, noting the wide differences in susceptibility of single strains and finding some to be relatively resistant. Clinical trials in the treatment of subacute bacterial endocarditis were begun in 1942. The earliest reports were somewhat discouraging,9 10 11 12 13 14 15 16 but they did suggest the possibility that larger doses of penicillin given over a longer time might produce better results. . . .
Dinaciclib induces immunogenic cell death and enhances anti-PD1–mediated tumor suppression
Authors: Dewan Md Sakib Hossain, Sarah Javaid, Mingmei Cai, Chunsheng Zhang, Anandi Sawant, Marlene Hinton, Manjiri Sathe, Jeff Grein, Wendy Blumenschein, Elaine M. Pinheiro, Alissa Chackerian
Journal: Journal of Clinical Investigation (2018)

Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1. Here, we observed antitumor activity following combinatorial therapy with anti-PD1 Ab and the cyclin-dependent kinase inhibitor dinaciclib in immunocompetent mouse tumor models. Dinaciclib induced a type I IFN gene signature within the tumor, leading us to hypothesize that dinaciclib potentiates the effects of anti-PD1 by eliciting ICD. Indeed, tumor cells treated with dinaciclib showed the hallmarks of ICD including surface calreticulin expression and release of high mobility group box 1 (HMGB1) and ATP. Mice treated with both anti-PD1 and dinaciclib showed increased T cell infiltration and DC activation within the tumor, indicating that this combination improves the overall quality of the immune response generated. These findings identify a potential mechanism for the observed benefit of combining dinaciclib and anti-PD1, in which dinaciclib induces ICD, thereby converting the tumor cell into an endogenous vaccine and boosting the effects of anti-PD1.
No Prognostic Significance of CD1a+ Dendritic Cells and CD8+ Tumor Infiltrating Lymphocytes in Mycosis Fungoides
Authors: G. Goteri, A. Filosa, L. M. ria Tarquini, R. Capretti, D. Stramazzotti, M. Offidani, G. Tucci, G. Filosa, M. Giangiacomi, S. Rupoli, P. Leoni
Journal: Blood (2002)
Ixazomib-Lenalidomide-Dexamethasone (IRd) Combination before and after Autologous Stem Cell Transplantation (ASCT) Followed By Ixazomib Maintenance Is a Safe and Effective Strategy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Phase 2 Study from the Intergroupe Francophone Du MyéLome (IFM)
Authors: Philippe Moreau, Cyrille Hulin, Denis Caillot, Gerald Marit, Aurore Perrot, Laurent Garderet, Thierry Facon, Lofti Benboubker, Lionel Karlin, Mourad Tiab, Bertrand Arnulf, Xavier Leleu, Cyrille Touzeau, Murielle Roussel, Lucie Planche, Hervé Avet-Loiseau, Thomas Dejoie, Michel Attal
Journal: Blood (2017)
Pulmonary Fibrous Nodule with Ossifications May Indicate Vascular Ehlers-Danlos Syndrome with Missense Mutation in <i>COL3A1</i>
Authors: Sabina Berezowska, Andreas Christe, Deborah Bartholdi, Markus Koch, Christophe von Garnier
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Epidermal melanocytes in segmental vitiligo show altered expression of E‐cadherin, but not P‐cadherin
Authors: C. Grill, L. Benzekri, A. Rubod, Z. Aktary, K. Ezzedine, A. Taïeb, Y. Gauthier, L. Larue, V. Delmas
Journal: British Journal of Dermatology (2018)

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Abstract 10859: Preventive Effects of Neopterin on Atherosclerosis
Authors: Remina Shirai, Kengo Sato, Kaho Watanabe, Rena Watanabe, Taka-aki Matsuyama, Shinji Koba, Tsutomu Hirano, Takuya Watanabe
Journal: Circulation (2015)

Introduction: Neopterin, a GTP metabolite produced by activated macrophages after stimulation by interferon-γ released by T cells, is expressed at high levels in the carotid atherosclerotic lesions in patients with angina pectoris. However, the modulatory effect of neopterin on atherogenesis has not yet been reported. Objective and Methods: We aimed to clarify the effects of neopterin on atherogenesis. We investigated the atheroprotective effects of neopterin on human umbilical vein endothelial cells (HUVECs), human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs) in vitro , and aortic lesions in ApoE -/- mice in vivo . Plasma neopterin levels were compared between 25 patients with acute coronary syndrome (ACS) and 15 healthy volunteers. Results: Neopterin attenuated TNF-α-mediated monocyte adhesion to HUVECs. Neopterin suppressed TNF-α-induced upregulation of MCP-1, ICAM-1, and VCAM-1 in HUVECs. Neopterin shifted the phenotype overwhelmingly to anti-inflammatory M2 rather than inflammatory M1 via NF-κB downregulation during differentiation of human monocytes into macrophages. Neoptein significantly suppressed oxidized LDL-induced foam cell formation associated with reduced CD36 expression and increased both expressions and activities of ABCA1 and ABCG1 in human monocyte-derived macrophages. Neopterin significantly suppressed angiotensin II-induced migration of HASMCs, but increased fibronectin and MMP2 expressions accompanied with enhanced MMP2 activity in HASMCs. Four-week-infusion of neopterin into ApoE -/- mice significantly retarded the development of aortic atherosclerotic lesions with reduced monocyte/macrophage infiltration and lowered plasma levels of total cholesterol. In addition, plasma neopterin levels were markedly increased in ACS patients than healthy volunteers, suggesting that neopterin increased to counteract the formation of atherothrombosis. Conclusions: Our results indicate that neopterin prevents atherogenesis by suppressing monocyte adhesion to endothelial cells, macrophage foam cell formation, and VSMC migration. Thus, neopterin could serve as a novel therapeutic target and potential biomarker for atherosclerotic cardiovascular diseases.
O Basic Surveillance Network, uma base de dados para os dados de vigilância das doenças transmissivéis
Authors: A Ternhag, A Tegnell, B Lesko, K Skaerlund, P Penttinen
Journal: Eurosurveillance (2004)

O Basic Surveillance Network comecou em 2000 e faz parte das redes sobre as doencas transmissiveis financiadas pela Commissao Europeia. A rede recolha e pom a disposicao dados de vigilância fundamental sobre doencas transmissiveis de todos os Estados membros da 'antiga' Uniao Europeia (antes de 2004). O objectivo e de fornecer um acesso comodo aos dados descriptivos ja disponiveis nas bases de dados nacionais, facilitando assim a monitorizacao e comparacao das tendencias da incidencia das doencas infecciosas nos Estados membros da UE. 
A lista das doencas infecciosas cobertas pela rede foi recentemente extendida das 10 doencas 'pilotas' iniciais a mais de 40 doencas que devem ser vigiladas. Os novos Estados membros vao ser convidados proximamente a participar a rede. 
Os dados sao basados sobre os casos e comprendem a data de aparicao da doenca, a idade e o sexo. So se recolhem algumas variaveis complementarias muito raras specificas para certas doencas, como o pais de contaminacao e o estatuto vacinal. A classificacao em casos possiveis, provaveis e confirmados corresponde as definicoes da UE. 
Os participantes podem aceder a um sitio Internet onde todos os dados estao presentados em forma de tabelas e graficos. Alem disso, existe um sitio acessivel ao publico https://www.eubsn.org./BSN/
High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients
Authors: Anne G. Vedel, Frederik Holmgaard, Lars S. Rasmussen, Annika Langkilde, Olaf B. Paulson, Theis Lange, Carsten Thomsen, Peter Skov Olsen, Hanne Berg Ravn, Jens C. Nilsson
Journal: Circulation (2018)

Background: Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. Methods: In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70–80 mm Hg) or lower (40–50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min −1 ·m −2 . The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging–evaluated total number of new ischemic lesions. Results: Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group ( P =0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm 3 (interquartile range, 0–118 mm 3 ; range, 0–25 261 mm 3 ) in the low-target group versus 29 mm 3 (interquartile range, 0–143 mm 3 ; range, 0–22 116 mm 3 ) in the high-target group (median difference estimate, 0; 95% confidence interval, −25 to 0.028; P =0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0–2; range, 0–24] versus 1 [interquartile range, 0–2; range, 0–29] respectively; median difference estimate, 0; 95% confidence interval, 0–0; P =0.71). No significant difference was observed in frequency of severe adverse events. Conclusions: Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02185885.
Soft Artificial Bladder Detrusor
Authors: Xuxu Yang, Chengrui An, Shuting Liu, Tingyu Cheng, Varitsara Bunpetch, Yixiao Liu, Shurong Dong, Shijian Li, Xiaohui Zou, Tiefeng Li, Hongwei Ouyang, Zhaohui Wu, Wei Yang
Journal: Advanced Healthcare Materials (2018)

Abstract Developing soft devices for invasive procedures bears great importance for human health. The softness and large strain actuation of responsive hydrogels promise the potential to fabricate soft devices, which can attach on and assist to the function of organs. The key challenges lie in the fabrication of soft devices with robust actuating ability and biocompatibility to the attached organ. This paper presents a solution that integrates the thermoresponsive hydrogel membrane with flexible electronics and silk scaffold into a balloon‐like soft device. As an example, the actuation assisting function of this soft device for shrinking an animal bladder is presented. The mechanical behaviors of the balloon‐like soft device are experimentally and theoretically investigated. The concepts are applicable to other applications such as soft implants, soft robotics, and microfluidics.
Speciated Pollen Season Parameters, Trends, and Associations with Temperature in the Contiguous United States
Authors: Jeremy J. Hess, Fiona Lo, Claudia L. Brown, Kristie L. Ebi, Arie Manangan, George Luber, Shubhayu Saha, Paul J. Schramm, Lewis Ziska, Cecilia Bitz
Journal: Journal of Allergy and Clinical Immunology (2018)
Cross-infection risk in patients with bronchiectasis: a position statement from the European Bronchiectasis Network (EMBARC), EMBARC/ELF patient advisory group and European Reference Network (ERN-Lung) Bronchiectasis Network
Authors: James D. Chalmers, Felix C. Ringshausen, Bridget Harris, J. Stuart Elborn, Annette Posthumus, Charles S. Haworth, Nicola Pilkington, Eva Polverino, Thomas Ruddy, Stefano Aliberti, Pieter C. Goeminne, Craig Winstanley, Anthony De Soyza
Journal: European Respiratory Journal (2018)

Involving patients in the design, conduct and dissemination of clinical research, clinical guidelines and education projects is highly beneficial, and is a priority for funders and societies such as the European Respiratory Society (ERS) [1]. Bronchiectasis is a lung condition associated with chronic cough and sputum production that is rapidly increasing in prevalence in Europe [2]. It is a neglected disease, but recent initiatives including the European Bronchiectasis Registry and research network (EMBARC) and the European Union supported European Reference Network for Rare Pulmonary Diseases (ERN-LUNG) are beginning to raise the diseases profile and stimulate new research [3, 4]. Patient involvement has been, and remains, central to these projects including the recently published European bronchiectasis guidelines which were developed with patients as members of the panel [5]. Risks of cross-infection in bronchiectasis are small, and should not currently restrict access to specialised care <http://ow.ly/dkVl30hcu5p> We acknowledge the EMBARC registry steering committee, the ERN-Lung bronchiectasis core network and ERN-Lung steering committee who approved this document. Bridget Harris, Nicola Pilkington, Annette Posthumus and Thomas Ruddy are representatives of the broader EMBARC/ELF bronchiectasis patient advisory group.
Investigating the Intracellular Behaviors of Liposomal Nanohybrids <i>via</i> SERS: Insights into the Influence of Metal Nanoparticles
Authors: Dan Zhu, Zhuyuan Wang, Shenfei Zong, Yizhi Zhang, Chen Chen, Ruohu Zhang, Binfeng Yun, Yiping Cui
Journal: Theranostics (2018)

The recent proposition to combine liposomes with nanoparticles presents great opportunities to develop multifunctional drug delivery platforms.Although impressive progress has been made, attempts to elucidate the role nanoparticles play in the integral nanohybrids are still rather limited.Here, using surface-enhanced Raman scattering (SERS) technique, we investigate the influence of metal nanoparticles on the liposomal properties, ranging from drug release to intracellular movement.Specifically, we prepared SERS-active nanohybrids by attaching metal nanoparticles to liposomes and employed SERS signals to explore the intracellular behavior of the nanohybrids.Once deposited on the cell membrane, the nanohybrids entered tumor cells via clathrin-mediated endocytosis and then moved to lysosomes.In comparison with pure liposomes, metal nanoparticles in the nanohybrids had little influence on the properties of liposomes.This study fills the gap of the function of nanoparticles in the overall nanohybrids, which provides a significant prerequisite for efficient drug delivery in therapeutic applications.
Abstract 13151: Can Depth of Chest Compressions Be Estimated From Compression-Induced Artifacts in the Thoracic Impedance or ECG Signal?
Authors: Chenguang Liu, Dawn Jorgenson, Stacy Gehman, Vijay Aditya Tadipatri
Journal: Circulation (2016)

Objective: To explore the feasibility of estimating chest compression depth (CD) by analyzing the compression-induced artifacts in the thoracic impedance (TI) or ECG signals from out-of-hospital cardiac arrest (OHCA) patients who receive manual CPR. Methods: Data from 641 OHCA patients was recorded by Philips MRx defibrillators with Q-CPR meters in 2011 and 2012. For each of the 94,566 extracted segments (6 seconds long) with chest compressions, the CD from the Q-CPR meter and the peak-peak value of TI signal (PPV-TI) were obtained. Univariate linear regression was performed between PPV-TI and CD for the whole population and the coefficient of determination ( R 2 ) was calculated. Linear regression was also performed in each of the individual patients who received at least 5 minutes of chest compressions (n=450). A subset of segments (n=608) were analyzed from asystolic patients (n=215), where the signals in the ECG were assumed to be compression-induced artifacts. In these segments, the CD and the peak-peak value of ECG signal (PPV-ECG) were obtained and linear regression was performed. Results: CD was 47 ± 11 mm (mean ± standard deviation). The R 2 between PPV-TI and CD was 0.05 (Figure 1A). For the segments with the 5% smallest PPV-TI, 18% of the compressions were deeper than 50 mm. The mean of R 2 between PPV-TI and CD in individual patients was 0.25 (Figure 1B), and 35.3% of the patients had an R 2 value smaller than 0.1. The R 2 between PPV-ECG and CD was 0.001 (Figure 1C). Conclusions: The linear correlation between PPV-TI and CD was low for the entire population. There was almost no correlation between PPV-ECG and CD. These results suggest that it is unreliable to estimate compression depth from the compression-induced artifacts in either the TI or ECG signal. Within individual patients, the R 2 of PPV-TI varied and was below 0.1 in &gt;35% of the patients, which suggests that estimating the trend of compression depth from the change of TI is not feasible in many patients.
Immunogenicity and safety of the multicomponent meningococcal B vaccine (4CMenB) in children and adolescents: a systematic review and meta-analysis
Authors: Maria Elena Flacco, Lamberto Manzoli, Annalisa Rosso, Carolina Marzuillo, Mauro Bergamini, Armando Stefanati, Rosario Cultrera, Paolo Villari, Walter Ricciardi, John P A Ioannidis, Despina G Contopoulos-Ioannidis
Journal: The Lancet Infectious Diseases (2018)
Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors
Authors: Erhao Zhang, Jieyi Gu, Hanmei Xu
Journal: Molecular Cancer (2018)

The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. This review focuses on different aspects of multiple mechanisms of immunosuppression in solid tumors. We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication.