tbuckley/cabot-search huggingface dataset:
A Mucin1 C-terminal Subunit-directed Monoclonal Antibody Targets Overexpressed Mucin1 in Breast Cancer
Authors: Guang Wu, Dongbum Kim, Jung Nam Kim, Sangkyu Park, Sony Maharjan, Heeju Koh, Kyungduk Moon, Younghee Lee, Hyung-Joo Kwon
Journal: Theranostics (2017)

Background: Mucin1 (MUC1) is a highly glycosylated transmembrane protein that has gained attention because of its overexpression in various cancers. However, MUC1-targeted therapeutic antibodies have not yet been approved for cancer therapy. MUC1 is cleaved to two subunits, MUC1-N and MCU1-C. MUC1-N is released from the cell surface, making MUC1-C a more reasonable target for cancer therapy. Therefore, we produced a monoclonal antibody (anti-hMUC1) specific to the extracellular region of MUC1-C and evaluated its effects in vitro and in vivo. Methods: We produced a monoclonal antibody (anti-hMUC1) using a purified recombinant human MUC1 polypeptide and our novel immunization protocol. The reactivity of anti-hMUC1 was characterized by ELISA, western blotting and immunoprecipitation analyses. The localization of the antibody in the breast cancer cells after binding was determined by confocal image analysis. The effects of the antibody on the growth of cells were also investigated. We injected anti-hMUC1 and performed in vivo tracing analysis in xenograft mouse models. In addition, expression of MUC1 in tissue sections from patients with breast cancer was assessed by immunohistochemistry with anti-hMUC1. Results: The anti-hMUC1 antibody recognized recombinant MUC1 as well as native MUC1-C protein in breast cancer cells. Anti-hMUC1 binds to the membrane surface of cells that express MUC1 and is internalized in some cancer cell lines. Treatment with anti-hMUC1 significantly reduced proliferation of cells in which anti-hMUC1 antibody is internalized. Furthermore, the anti-hMUC1 antibody was specifically localized in the MUC1-expressing breast cancer cell-derived tumors in xenograft mouse models. Based on immunohistochemistry analysis, we detected significantly higher expression of MUC1 in cancer tissues than in normal control tissues. Conclusion: Our results reveal that the anti-hMUC1 antibody targets the extracellular region of MUC1-C subunit and may have utility in future applications as an anti-breast cancer agent.
Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis
Authors: Kutaiba Alhaj Hussen, Thien-Phong Vu Manh, Fabien Guimiot, Elisabeth Nelson, Emna Chabaane, Marc Delord, Maxime Barbier, Claire Berthault, Nicolas Dulphy, Antonio José Alberdi, Odile Burlen-Defranoux, Gerard Socié, Jean Christophe Bories, Jerôme Larghero, Valérie Vanneaux, Els Verhoeyen, Thierry Wirth, Marc Dalod, Jean Claude Gluckman, Ana Cumano, Bruno Canque
Journal: Immunity (2017)
Timeliness of Receipt of Early Childhood Vaccinations Among Children of Immigrants — Minnesota, 2016
Authors: Maureen Leeds, Miriam Halstead Muscoplat
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Receiving recommended childhood vaccinations on schedule is the best way to prevent the occurrence and spread of vaccine-preventable diseases (1). Vaccination coverage among children aged 19-35 months in the United States exceeds 90% for most recommended vaccines in the early childhood series (2); however, previous studies have found that few children receive all recommended vaccine doses on time (3). The Minnesota Department of Health (MDH), using information from the Minnesota Immunization Information Connection (MIIC) and the MDH Office of Vital Records, examined early childhood immunization rates and found that children with at least one foreign-born parent were less likely to be up-to-date on recommended immunizations at ages 2, 6, 18, and 36 months than were children with two U.S.-born parents. Vaccination coverage at age 36 months varied by mother's region of origin, ranging from 77.5% among children born to mothers from Central and South America and the Caribbean to 44.2% among children born to mothers from Somalia. Low vaccination coverage in these communities puts susceptible children and adults at risk for outbreaks of vaccine-preventable diseases, as evidenced by the recent measles outbreak in Minnesota (4). Increased outreach to immigrant, migrant, and refugee populations and other populations with low up-to-date vaccination rates might improve timely vaccination in these communities.
TCT-768 Risk Adjustment Model for 30-Day Mortality After Transcatheter Aortic Valve Replacement. A Report from the STS/ACC TVT RegistryTM
Authors: Suzanne Arnold, Sean O'Brien, Sreekanth Vemulapalli, David Cohen, Amanda Stebbins, Rosemarie Hakim, David Holmes, Vinod Thourani, Fred Edwards
Journal: Journal of the American College of Cardiology (2017)
Investigating the molecular dissolution process of binary solid dispersions by molecular dynamics simulations
Authors: TengIan Chan, Defang Ouyang
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Dissolution molecular mechanism of solid dispersions still remains unclear despite thousands of reports about this technique. The aim of current research was to investigate the molecular dissolution mechanism of solid dispersions by molecular dynamics simulations. The formation of ibuprofen/polymer solid dispersions was modeled by the simulated annealing method. After that, the models of solid dispersions were immersed into the water box with 25–30 Å thicknesses and 50–100 ns MD simulations were performed to all systems. Simulation results showed various dissolution behaviors in different particle sizes and various polymers of solid dispersions. Small-sized particles of solid dispersions dissolved quickly in the water, while the large particles of PEG or PVP-containing solid dispersions gradually swelled in the dissolution process and drug molecules may aggregate together. In the dissolution process, the carboxylic groups of ibuprofen molecules turned its direction from polymer molecules to external water box and then the drug molecules left the polymer coils. At the same time, polymer coils gradually relaxed and became free polymer chains in the solution. In addition, solid dispersion with poloxamer could prevent the precipitate of drug molecules in the dissolution process, which is different from those of PEG or PVP-containing systems. This research provided us clear images of dissolution process of solid dispersions at the molecular level.
TCT-724 Impact of Coronary Calcification Severity on Clinical Outcomes After Contemporary PCI – Insights From the CHAMPION PHOENIX Trial
Authors: Philippe Genereux, Bjorn Redfors, Gregg Stone, Philippe Gabriel Steg, C. Michael Gibson, Christian Hamm, Matthew Price, Jayne Prats, Harvey White, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2017)
Long-Term Results of the FOLL05 Trial Comparing R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Symptomatic Follicular Lymphoma
Authors: Stefano Luminari, Angela Ferrari, Martina Manni, Alessandra Dondi, Annalisa Chiarenza, Francesco Merli, Chiara Rusconi, Vittoria Tarantino, Alessandra Tucci, Umberto Vitolo, Sofia Kovalchuk, Emanuele Angelucci, Alessandro Pulsoni, Luca Arcaini, Francesco Angrilli, Gianluca Gaidano, Caterina Stelitano, Giovanni Bertoldero, Nicola Cascavilla, Flavia Salvi, Andrés J.M. Ferreri, Daniele Vallisa, Luigi Marcheselli, Massimo Federico
Journal: Journal of Clinical Oncology (2017)

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy.
Abstract 14789: A Rare Case of Primary Cardiac Leiomyosarcoma Involving the Left Ventricle
Authors: Hafiz D Khalid, Danielle S Grunloh, Ahsan M Bhatti, Benjamin J Rhee, Sarwar Orakzai
Journal: Circulation (2014)

Case Report: A 73 year old female was admitted to our hospital with complaints of acute shortness of breath on exertion and chest tightness accompanied with non-exertional left arm pain. Her prior history was significant for hypertension. Vital signs were significant for tachycardia. EKG revealed sinus tachycardia and low voltage QRS complexes. Cardiac Biomarkers were negative. CXR on admission showed massive cardiomegaly. (A) Echocardiography, Off Axis, Apical long axis view showing a large mass attached to the LV apex surrounded by large pericardial effusion. Pericardiocentesis was performed and 1200ml of bloody fluid was removed. (B) Cardiac MRI was performed which revealed a mass arising from the inferolateral wall of Left Ventricle measuring 6.5x4.9x6.2 cm Left thoracotomy, wedge biopsy of left ventricular mass was performed. (C, D)Pathological analysis confirmed well differentiated Leiomyosarcoma (grade 1 of 3) FNCLCC grading system. Tumor was strongly positive for vimentin, smooth muscle myosin and desmin.
Mathematical coupling causes spurious correlation within the conventional acute-to-chronic workload ratio calculations
Authors: Lorenzo Lolli, Alan M Batterham, Richard Hawkins, David M Kelly, Anthony J Strudwick, Robin Thorpe, Warren Gregson, Greg Atkinson
Journal: British Journal of Sports Medicine (2017)

The monitoring of training loads is now a much-researched topic in team sports.1 Within this topic, researchers and practitioners are particularly interested in the impact of relatively short (acute) periods of higher training loads normalised for the prior and longer term (chronic) loads. In recent years, a well-established approach for normalising this acute ‘spike’ to chronic  has been by calculating the ‘acute:chronic workload ratio’ (ACWR). Importantly, the term load was retained given its common use in this research area. Both this index and chronic  itself have been reported to be independent predictors of training-related injuries.2 It has also been reported, particularly in team sports competitors, that there are associations between acute spikes in training loads (relative to chronic loads) and time-loss injuries.1

The ACWR is usually calculated as the simple ratio of recent (ie, 1 week) to longer term (ie, 4 weeks) training loads.1 While it is important for the numerator and denominator of any ratio to be correlated only through biological mechanisms,3 one aspect of the ACWR calculation is that the acute  also constitutes a substantial …
Abstract 19440: Dichloroacetate Fails to Improve Exaggerated Chronic-Hypoxia Induced Pulmonary Hypertension in Sirtuin 1 Mutant Mice
Authors: Mohamad Taha, Yupu Deng, Michael W McBurney, Duncan J Stewart
Journal: Circulation (2016)

Background: Pulmonary Hypertension (PH) is caused by remodelling of pulmonary arterioles, leading to increased pulmonary vascular resistance, right ventricle hypertrophy and eventually heart failur...
TCT-153 Clinical, social, and behavioral predictors of the increased risk of cardiac events after PCI in minority women: A subanalysis of the PLATINUM Diversity study
Authors: Scott Davis, Sandeep Nathan, Roger Hill, Steven Hearne, Vince Vismara, Jerome Williams, Robert Pyo, Elie Gharib, Zafir Hawa, Paul Underwood, Dominic Allocco, Wayne Batchelor, Roxana Mehran
Journal: Journal of the American College of Cardiology (2017)
Effect of Patient Navigation and Financial Incentives on Smoking Cessation Among Primary Care Patients at an Urban Safety-Net Hospital
Authors: Karen E. Lasser, Lisa M. Quintiliani, Ve Truong, Ziming Xuan, Jennifer Murillo, Cheryl Jean, Lori Pbert
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> While the proportion of adults who smoke cigarettes has declined substantially in the past decade, socioeconomic disparities in cigarette smoking remain. Few interventions have targeted low socioeconomic status (SES) and minority smokers in primary care settings. <h3>Objective</h3> To evaluate a multicomponent intervention to promote smoking cessation among low-SES and minority smokers. <h3>Design, Setting, and Participants</h3> For this prospective, unblinded, randomized clinical trial conducted between May 1, 2015, and September 4, 2017, adults 18 years and older who spoke English, smoked 10 or more cigarettes per day in the past week, were contemplating or preparing to quit smoking, and had a primary care clinician were recruited from general internal medicine and family medicine practices at 1 large safety-net hospital in Boston, Massachusetts. <h3>Interventions</h3> Patients were randomized to a control group that received an enhancement of usual care (n = 175 participants) or to an intervention group that received up to 4 hours of patient navigation delivered over 6 months in addition to usual care, as well as financial incentives for biochemically confirmed smoking cessation at 6 and 12 months following enrollment (n = 177 participants). <h3>Main Outcomes and Measures</h3> The primary outcome determined a priori was biochemically confirmed smoking cessation at 12 months. <h3>Results</h3> Among 352 patients who were randomized (mean [SD] age, 50.0 [11.0] years; 191 women [54.3%]; 197 participants who identified as non–Hispanic black [56.0%]; 40 participants who identified as Hispanic of any race [11.4%]), all were included in the intention-to-treat analysis. At 12 months following enrollment, 21 participants [11.9%] in the navigation and incentives group, compared with 4 participants [2.3%] in the control group, had quit smoking (odds ratio, 5.8; 95% CI, 1.9-17.1; number needed to treat, 10.4;<i>P</i> &lt; .001). In prespecified subgroup analyses, the intervention was particularly beneficial for older participants (19 [19.8%] vs 1 [1.0%];<i>P</i> &lt; .001), women (17 [16.8%] vs 2 [2.2%];<i>P</i> &lt; .001), participants with household yearly income of $20 000 or less (15 [15.5%] vs 3 [3.1%];<i>P</i> = .003), and nonwhite participants (21 [15.2%] vs 4 [3.0%];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this study of adult daily smokers at 1 large urban safety-net hospital, patient navigation and financial incentives for smoking cessation significantly increased the rates of smoking cessation. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02351609
Sputum cell IL-1 receptor expression level is a marker of airway neutrophilia and airflow obstruction in asthmatic patients
Authors: Michael D. Evans, Stephane Esnault, Loren C. Denlinger, Nizar N. Jarjour
Journal: Journal of Allergy and Clinical Immunology (2017)

Various clinical, biologic, or physiologic markers of asthma have been used to identify patient clusters and potential targets for therapy. However, these identifiers frequently overlap among the different asthma groups. For instance, both eosinophil and neutrophil counts are often increased in the airways of asthmatic patients despite their typical association with type 2 and type 17 immune response, respectively.We sought to determine whether inflammatory gene expression is related to patterns of airway inflammation and lung function and identify molecular markers for neutrophilic asthma.Expression levels of 17 genes characterizing type 1, type 2, and type 17 lymphocytes were measured in sputum samples from 48 participants with asthma. The relationships between gene expression levels and sputum cell differentials or measures of pulmonary function were examined by using partial least squares regression.Gene expression levels were strongly associated with cell differentials, explaining 71% of variation in eosinophil counts and 64% of variation in neutrophil counts. The 3 genes with the strongest relationships to sputum neutrophil counts were IL1R1 (standardized regression coefficient [β] = +0.27, P = .005), IL1RAP (β = +0.32, P = .0004), and IL4R (β = +0.29, P = .002). Higher expression levels of IL1R1, IL1RAP, and IL4R were associated with reduced FEV1/forced vital capacity ratio (β = -0.11, -0.08, and -0.10; P = .005, .07, and .05).IL-1 receptor appears to be a marker of neutrophilic inflammation and airflow obstruction in patients with asthma, who have a wide range of disease severity. The IL-1 pathway might contribute to airway neutrophilia and is a potential therapeutic target in patients with neutrophilic asthma.
Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair <i>via </i>Modulation of Macrophages
Authors: Jingli Chen, Jun Yang, Ruiyuan Liu, Chenmeng Qiao, Zhiguo Lu, Yuanjie Shi, Zhanming Fan, Zhenzhong Zhang, Xin Zhang
Journal: Theranostics (2017)

Currently unsatisfactory treatment of myocardial infarction (MI) is due to the unbridled inflammation and the delayed diagnosis at the early stage. To address these problems, firstly, phosphatidylserine (PS) was used to modulate the phenotypes of macrophages (MΦ) and resolve the early inflammation via binding to PS receptors (PSR) on macrophage surface. Secondly, highly-sensitive magnetic iron oxide nanocubes (MIONs) were adopted to realize the early visualization via magnetic resonance imaging (MRI). However, the major drawback for MIONs as contrast agents was their hydrophobic properties and insufficient delivery. Hence, zwitterionic biodegradable copolymer poly(lactide)-polycarboxybetaine (PLA-PCB, PP), companied with PS, was used to provide a good colloidal stability and long blood circulation for the nanocubes. Given the above, a theranostic nanosystem (PP/PS@MIONs) was constructed for early treatment of MI. With external magnetic field-induced targeting and PS targeting, the nanosystem enhanced the accumulation in infarcted area, and accelerated the resolution of early inflammatory responses. Moreover, the nanocubes in system were promoted to escape from endosomes/lysosomes via protonation of PCB, which contributes to accurate MRI. This nanosystem showed good inflammation-resolving effects and imaging ability in MI model rats. Therefore, this theranostic nanosystem can realize accurate visualization and significantly improve the treatment efficacy of MI at early stage.
Dual-targeting Wnt and uPA receptors using peptide conjugated ultra-small nanoparticle drug carriers inhibited cancer stem-cell phenotype in chemo-resistant breast cancer
Authors: Jasmine Miller-Kleinhenz, Xiangxue Guo, Weiping Qian, Hongyu Zhou, Erica N. Bozeman, Lei Zhu, Xin Ji, Y.Andrew Wang, Toncred Styblo, Ruth O'Regan, Hui Mao, Lily Yang
Journal: Biomaterials (2017)
Randomized phase II open-label study of abiraterone acetate (AA) plus low-dose prednisone (P) with or without exemestane (E) in postmenopausal women with ER+ metastatic breast cancer (MBC) progressing after letrozole or anastrozole therapy.
Authors: Joyce O'Shaughnessy, Margaret K. Yu, Jill Kearney, Julie S. Larsen, Arturo Molina, Stephen R. D. Johnston
Journal: Journal of Clinical Oncology (2012)

TPS666 Background: AA plus P treatment in men with metastatic castration-resistant prostate cancer has demonstrated a survival advantage over P alone. Circulating adrenal steroids including DHEA and DHEA-sulfate can stimulate proliferation of breast cancer cell lines in a low-estrogen environment. Thus, it is hypothesized that depletion of adrenal androgens as well as estrogens by AA, a potent CYP17 inhibitor, inhibits tumor growth by disruption of ER-dependent growth signaling. In a previously reported phase I study of AA in patients (pts) with breast cancer (Basu, ASCO 2011), 2/21 pts who were ER+ were on study for ≥ 11 months; 1 had a confirmed PR and continued on treatment &gt; 14 months. Mechanism-based adverse event of grade 3/4 hypokalemia occurred in 4 pts and was managed with potassium supplementation and low dose corticosteroids. Methods: In the current study, 300 postmenopausal women with ER+ Her2- MBC progressing after letrozole or anastrozole are randomized to either AA 1000 mg + P 5 mg daily or AA + P + E 25 mg daily vs E. Disease must have been sensitive to a non-steroidal aromatase inhibitor (AI) prior to study entry. Subjects are stratified by number of prior therapies and by AI use in adjuvant or metastatic setting. Central review of tissue is required prior to randomization. Gene expression profiling (GEP) (AR, ER, PR, Her2, CYP17, Ki-67, CYP 19, and 3-β-HSD) will be performed on FFPE archival tissue. Pre- and post-treatment circulating tumor cells and fresh tumor biopsies will also be obtained for GEP in a subset of pts. Primary endpoint is PFS. Secondary endpoints are OS, ORR, patient reported outcomes, changes in endocrine markers, and PK characterization of AA and E. Subjects randomized to E may crossover to AA + P at time of disease progression. One interim analysis is scheduled after 50% of PFS events have occurred. After review of interim data, the Data Review Committee will make recommendations regarding study continuation. 23pts from 45 active sites have been randomized as of January 24,2012. (ClinicalTrials.gov Identifier: NCT01381874)
Vigilância da listeriose na Europa
Authors: H de Valk, C Jacquet, V Goulet, V Vaillant, A Perra, F Simon, J C Desenclos, P Martin
Journal: Eurosurveillance (2005)

Alem do impacto economico e da ameaca associada com os surtos, a listeriose representa um problema importante de saude publica, devido a sua taxa de letalidade entre as mais altas de todas as infeccoes transmitidas por alimentos (20-30%), e ao seu alto potencial epidemico. A evolucao dos metodos de producao dos alimentos, tal como a distribuicao e o armazenamento, facilitaram a ocorrencia de surtos afetando numerosos paises. Em 2002, um estudo foi levado a cabo para avaliar a necessidade e a viabilidade de uma rede europeia sobre as infeccoes humanas por Listeria. Os dados sobre os sistemas de vigilância e os metodos de laboratorio foram recolhidos por meio de dois questionarios mandados aos Centros nacionais de vigilância de doencas transmissiveis e aos laboratorios de referencia de Listeria. Em 16 paises entre os 17 questionados, existiam sistemas de vigilância da listeriose e 16 paises tinham um laboratorio nacional de referencia (LNR). Em todos os paises, a definicao de caso estava basada no isolamento de Listeria monocytogenes. Quatorze LNR realizavam ao menos um metodo de tipificacao das estirpes humanas. Treze paises ao menos ja levavam a cabo, ou iam faze-lo, a caracterizacao dos isolados das estirpes humanas por electroforese em campo pulsatil (PFGE) seguindo um protocolo estandardizado. Para os paises participantes, a existencia de uma rede de vigilância europeia da listeriose seria um verdadeiro valor acrescentado, especialmente para a deteccao e a investigacao de surtos. Tambem confirmaram a viabilidade de uma rede de vigilância basada nos programas nacionais existentes.