tbuckley/cabot-search huggingface dataset:
A Multifunctional Micellar Nanoplatform with pH‐Triggered Cell Penetration and Nuclear Targeting for Effective Cancer Therapy and Inhibition to Lung Metastasis
Authors: Yuting Jing, Xiang Xiong, Yang Ming, Jingya Zhao, Xing Guo, Guang Yang, Shaobing Zhou
Journal: Advanced Healthcare Materials (2018)

Abstract The enhancement of cellular internalization and subsequent achievement of a nuclear targeting of nanocarriers play an important role in maximizing the therapeutic potency and minimizing the side effects of encapsulated drugs. Herein, a multifunctional micellar nanoplatform simultaneously with high cell penetration and nuclear targeting through pH‐triggered surface charge reversal is presented. The miscellar system is constructed from poly(ethylene glycol)‐poly(ε‐caprolactone) with 2,3‐dimethylmaleic anhydride‐Tat decoration (PECL/DA‐Tat). DA groups are used to mask the positive charge of Tat to prolong blood circulation of the nanocarriers. In the mildly acidic environment of tumor tissue, the system exhibits ultrasensitive negative to positive charge reversal, facilitating the cell internalization and subsequent nuclear targeting. The chemotherapeutic 10‐hydroxycamptothecin conjugated to methoxy polyethylene glycol, which is loaded in this micelle, obviously enhances cytotoxicity against tumor cells. The in vivo therapy in mice bearing 4T1 breast tumor reveals that the system has a significant enhancement of both the endocytosis and nuclear enrichment, showing a highly effective antitumor efficacy and inhibition to lung metastasis.
N-cadherin suppresses AKT and enhances ERK activation to promote mammary tumor invasion and metastasis
Authors: su chung, James Hulit, Kimita Suyama, Rachel Hazan
Journal: Cancer Research (2008)

5359   N-cadherin is a cell-cell adhesion molecule that was shown to promote motility, invasion, and metastasis. N-cadherin is upregulated in invasive breast cancer cell lines and tumors. However, the mechanism by which N-cadherin promotes metastasis remains to be further elucidated. In vitro studies have suggested that N-cadherin maybe enhancing metastasis by potentiating the FGFR-ERK-MMP-9 signaling axis. These findings were validated in vivo in the polyoma middle T (PyMT) tumor model, in which N-cadherin mammary expression led to increased lung metastasis. This effect was due to ERK pathway activation by N-cadherin leading to matrix metalloproteinase 9 (MMP-9) expression and cellular invasion.  How N-cadherin precisely regulates metastasis remains to be further addressed. It appears that in addition to activating the ERK pathway, N-cadherin is also suppressing AKT1 activation, which has been shown to suppress motility and invasion. In the PyMT model, mammary tumor lysates from PyMT-N-cad expressed reduced levels of phosphorylated AKT compared to PyMT controls. Moreover, overexpression of N-cadherin into a PyMT tumor cell line suppressed AKT phosphorylation while it increased invasiveness in vitro. Consistent with these data, treating a breast cancer cell line overexpressing N-cadherin (MCF-7-N-cad cells) with LY294002, a PI3K inhibitor, leads to increases in FGF stimulated ERK phosphorylation, MMP-9 expression, and invasion. In conclusion, our data suggests that the activation of the ERK pathway and the suppression of the AKT pathway by N-cadherin promote metastasis in vivo.
Greater Treatment Benefit with Omalizumab in Children with Increased Asthma Severity: Exploratory Analyses from the Inner-City Anti-IgE Therapy for Asthma (ICATA) Study
Authors: William W. Busse, Tmirah Haselkorn, Karin Rosén, Benjamin L. Trzaskoma, Benjamin Ortiz, Stanley J. Szefler
Journal: Journal of Allergy and Clinical Immunology (2018)
Sputum cytology during late‐phase responses to inhalation challenge with different allergens
Authors: J. A. Revez, K. J. Killian, P. M. O'Byrne, L.‐P. Boulet, J. W. Upham, G. M. Gauvreau, M. A. R. Ferreira
Journal: Allergy (2018)

Abstract Background In mouse models of allergic asthma, exposure to different allergens can trigger distinct inflammatory subtypes in the airways. We investigated whether this observation extends to humans. Methods We compared the frequency of sputum inflammatory subtypes between mild allergic asthma subjects (n = 129) exposed to different allergens in inhalation challenge tests. These tests were performed using a standardized protocol as part of clinical trials of experimental treatments for asthma, prior to drug randomization. Five allergen types were represented: the house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae , ragweed, grass, and cat. Results Of 118 individuals with a sputum sample collected before allergen challenge (baseline), 45 (38%) had paucigranulocytic, 51 (43%) eosinophilic, 11 (9%) neutrophilic, and 11 (9%) mixed granulocytic sputum. Of note, most individuals with baseline paucigranulocytic sputum developed eosinophilic (48%) or mixed granulocytic (43%) sputum 7 hours after allergen challenge, highlighting the dynamic nature of sputum inflammatory subtype in asthma. Overall, there was no difference in the frequency of sputum inflammatory subtypes following challenge with different allergen types. Similar results were observed at 24 hours after allergen challenge. Conclusions Unlike reported in mice, in humans the sputum inflammatory subtype observed after an allergen‐induced asthma exacerbation is unlikely to be influenced by the type of allergen used.
Agent-Based Modeling in Public Health: Current Applications and Future Directions
Authors: Melissa Tracy, Magdalena Cerdá, Katherine M. Keyes
Journal: Annual Review of Public Health (2018)

Agent-based modeling is a computational approach in which agents with a specified set of characteristics interact with each other and with their environment according to predefined rules. We review key areas in public health where agent-based modeling has been adopted, including both communicable and noncommunicable disease, health behaviors, and social epidemiology. We also describe the main strengths and limitations of this approach for questions with public health relevance. Finally, we describe both methodologic and substantive future directions that we believe will enhance the value of agent-based modeling for public health. In particular, advances in model validation, comparisons with other causal modeling procedures, and the expansion of the models to consider comorbidity and joint influences more systematically will improve the utility of this approach to inform public health research, practice, and policy.
Erratum: Corrigendum: High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma
Authors: Carsten Linnemann, Marit M van Buuren, Laura Bies, Els M E Verdegaal, Remko Schotte, Jorg J A Calis, Sam Behjati, Arno Velds, Henk Hilkmann, Dris el Atmioui, Marten Visser, Michael R Stratton, John B A G Haanen, Hergen Spits, Sjoerd H van der Burg, Ton N M Schumacher
Journal: Nature Medicine (2016)
Long Noncoding RNA pancEts-1 Promotes Neuroblastoma Progression through hnRNPK-Mediated β-Catenin Stabilization
Authors: Dan Li, Xiaojing Wang, Hong Mei, Erhu Fang, Lin Ye, Huajie Song, Feng Yang, Huanhuan Li, Kai Huang, Liduan Zheng, Qiangsong Tong
Journal: Cancer Research (2018)

Long noncoding RNAs (lncRNA) play essential roles in tumor progression. However, the functions of lncRNAs in the tumorigenesis and aggressiveness of neuroblastoma still remain to be determined. Here, we report the identification of lncRNA pancEts-1 as a novel driver of neuroblastoma progression by using a public microarray dataset. LncRNA pancEts-1 promoted the growth, invasion, and metastasis of neuroblastoma cells in vitro and in vivo Mechanistically, pancEts-1 bound to hnRNPK to facilitate its physical interaction with β-catenin, whereas hnRNPK stabilized the β-catenin by inhibiting proteasome-mediated degradation, resulting in transcriptional alteration of target genes associated with neuroblastoma progression. Both pancEts-1 and hnRNPK were upregulated in clinical neuroblastoma tissues, and were associated with unfavorable outcome of patients. Overall, our results define an oncogenic role of pancEts-1 in neuroblastoma progression through hnRNPK-mediated β-catenin stabilization, with potential implications for the clinical therapeutics of neuroblastoma.Significance: These findings reveal the oncogenic functions of a long noncoding RNA in neuroblastoma progression, offering a potential target for clinical therapeutics. Cancer Res; 78(5); 1169-83. ©2018 AACR.
How Much Do We Spend? Creating Historical Estimates of Public Health Expenditures in the United States at the Federal, State, and Local Levels
Authors: Jonathon P. Leider, Beth Resnick, David Bishai, F. Douglas Scutchfield
Journal: Annual Review of Public Health (2018)

The United States has a complex governmental public health system. Agencies at the federal, state, and local levels all contribute to the protection and promotion of the population's health. Whether the modern public health system is well situated to deliver essential public health services, however, is an open question. In some part, its readiness relates to how agencies are funded and to what ends. A mix of Federalism, home rule, and happenstance has contributed to a siloed funding system in the United States, whereby health agencies are given particular dollars for particular tasks. Little discretionary funding remains. Furthermore, tracking how much is spent, by whom, and on what is notoriously challenging. This review both outlines the challenges associated with estimating public health spending and explains the known sources of funding that are used to estimate and demonstrate the value of public health spending.
Correction: Covered vs. uncovered self-expandable metal stents for malignant distal biliary strictures: a systematic review and meta-analysis
Authors: Alberto Tringali, Cesare Hassan, Matteo Rota, Marta Rossi, Massimiliano Mutignani, Lars Aabakken
Journal: Endoscopy (2018)

Corrected by: Covered vs. uncovered self-expandable metal stents for malignant distal biliary strictures: a systematic review and meta-analysisEndoscopy 2018; 50(06): 631-641DOI: 10.1055/s-0043-125062
Association of Lower Diagnostic Yield With High Users of CT Pulmonary Angiogram
Authors: Jaron Chong, Todd C. Lee, Armen Attarian, Lojan Sivakumaran, Jean-Marc Troquet, Emily G. McDonald, Benoît Gallix
Journal: JAMA Internal Medicine (2018)

This study examines interphysician variability of diagnostic yield in computed tomographic pulmonary angiogram for pulmonary emboli.
A phase 1 study of eribulin mesylate (E7389), a novel microtubule targeting chemotherapeutic agent in children with refractory or recurrent solid tumors (excluding CNS), including lymphomas: a Children's Oncology Group Phase 1 Consortium study (ADVL1314).
Authors: Eric Schafer, Rachel E. Rau, Xiaowei Liu, Charles G. Minard, David R. D'Adamo, Rachael Scott, Larisa Reyderman, Gresel Minette V. Martinez, Elizabeth Fox, Brenda Weigel, Susan Blaney
Journal: Journal of Clinical Oncology (2016)

2567 Background: Eribulin mesylate, a synthetic analog of Halichondrin B, is a novel microtubule dynamics inhibitor. It inhibits microtubule growth without effects on microtubule shortening and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid tumors, including lymphomas. Methods: Eribulin was administered intravenously on days 1 and 8 in 21-day cycles. Three dose levels (1.1, 1.4 and 1.8 mg/m2/dose) were evaluated using the rolling-6 design with additional patients enrolled into a PK expansion cohort at the MTD/recommended phase 2 dose (RP2D). PK samples were obtained following the Day 1 dose of cycle 1. Results: To date, 23 patients ages 3-17 (median 14) years have been enrolled, with 21 fully evaluable for toxicity. Subjects enrolled with 10 unique tumor types the most common of which were osteosarcoma (n = 9) and Ewing sarcoma (n = 4). During the dose escalation phase, DLTs occurred in 0/6 and 1/6 subjects at 1.1 and 1.4 mg/m2/dose, respectively. At 1.8 mg/m2/dose 2/5 subjects experienced dose-limiting (grade 4) neutropenia. The DLTs, which occurred in a single patient at 1.4 mg/m2/dose, included Grade 4 neutropenia and Grade 3 fatigue. No further DLTs have been observed in the expansion cohort at 1.4 mg/m2/dose. Grade 3/4 non-DLT non-hematologic toxicities across all dose levels and cycles included increases in ALT and AST, anorexia, nausea and hypokalemia. No episodes of ≥ Gr 2 QTc prolongation or peripheral neuropathy were reported. Eribulin exposure was dose-dependent and elimination half-life was ~36hr. Conclusions: Eribulin was well-tolerated in children with refractory/recurrent solid tumors with neutropenia identified as the primary DLT. The RP2D of eribulin mesylate is 1.4 mg/m2/dose on days 1 and 8 of a 21-day cycle. Clinical trial information: NCT02171260.
The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans
Authors: Sarah Ringold, Peter A. Nigrovic, Brian M. Feldman, George A. Tomlinson, Emily von Scheven, Carol A. Wallace, Adam M. Huber, Laura E. Schanberg, Suzanne C. Li, Pamela F. Weiss, Robert C. Fuhlbrigge, Esi M. Morgan, Yukiko Kimura
Journal: Arthritis & Rheumatology (2018)

The pediatric rheumatic diseases are a heterogeneous group of rare diseases, posing a number of challenges for the use of traditional clinical and translational research methods. Innovative comparative effectiveness approaches are needed to efficiently study treatment strategies and disease outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the consensus treatment plan (CTP) approach as a comparative effectiveness tool for research in pediatric rheumatology. CTPs are treatment strategies, developed by consensus methods among CARRA members, intended to reduce variation in treatment approaches, standardize outcome measurements, and allow for comparison of the effectiveness of different approaches with the goal of improving disease outcomes. To date, CTPs have been published for 8 different diseases and disease manifestations. The approach has been successfully piloted for juvenile localized scleroderma, systemic juvenile idiopathic arthritis (JIA), polyarticular JIA, dermatomyositis, and lupus nephritis. Large-scale studies are underway for systemic JIA and polyarticular JIA, with the CARRA patient registry serving as the data collection platform. These studies have been designed with stakeholder involvement, including active input from CARRA providers, patients, and parents, with the goal of increasing feasibility and ensuring the relevance of the outcomes. These studies include ancillary biologic specimen collection intended to support additional translational and mechanistic studies. Data from these ongoing CTP studies will provide more information on the ability of this approach to identify effective treatment strategies and improve outcomes in the pediatric rheumatic diseases.
Changes in Hospital–Physician Affiliations in U.S. Hospitals
Authors: Alan R. Ertle
Journal: Annals of Internal Medicine (2018)

Letters16 January 2018Changes in Hospital–Physician Affiliations in U.S. HospitalsAlan R. Ertle, MD, MPH, MBAAlan R. Ertle, MD, MPH, MBAMercy Medical Group, Sacramento, California (A.R.E.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0684 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Scott and colleagues' findings (1) are not particularly surprising. Employment by hospital systems alone does not necessarily affect the quality of care provided. Belief that it does is partly based on the authors' false assumption that hospital-employed physicians “are less likely to focus on generating revenue to maintain an independent practice and more likely to focus on patient care.” This statement seems to assume that these employment arrangements are based on salary rather than productivity. In general, physician employment agreements with hospitals remain largely productivity-based (dependent on, for example, encounters and work relative value units). On the ...Reference1. Scott KW, Orav EJ, Cutler DM, Jha AK. Changes in hospital–physician affiliations in U.S. hospitals and their effect on quality of care. Ann Intern Med. 2017;166:1-8. [PMID: 27654704]. doi:10.7326/M16-0125 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Mercy Medical Group, Sacramento, California (A.R.E.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0684. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoChanges in Hospital–Physician Affiliations in U.S. Hospitals and Their Effect on Quality of Care Kirstin W. Scott , E. John Orav , David M. Cutler , and Ashish K. Jha Changes in Hospital–Physician Affiliations in U.S. Hospitals Russell L. Bedsole Changes in Hospital–Physician Affiliations in U.S. Hospitals Kirstin W. Scott , E. John Orav , David M. Cutler , and Ashish K. Jha Changes in Hospital–Physician Affiliations in U.S. Hospitals Edward Ringel Metrics 16 January 2018Volume 168, Issue 2Page: 155-156KeywordsConflicts of interestDisclosureHealth care qualityPatientsRivers ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cytokines (IL-15, IL-18, IFNγ) and Vitamin D3 Increase Expression of Inducible Nitric Oxide Synthase (iNOS) by Monocytes from IgE+ Adults with Asthma
Authors: Maja Nowakowski, Brian Goodman, Adam El Sehamy, Stephen R. McCormick, Seto M. Chice, Helen G. Durkin, Rauno O. Joks
Journal: Journal of Allergy and Clinical Immunology (2018)
Gelatin- hydroxyapatite- calcium sulphate based biomaterial for long term sustained delivery of bone morphogenic protein-2 and zoledronic acid for increased bone formation: In-vitro and in-vivo carrier properties
Authors: Deepak Bushan Raina, David Larsson, Filip Mrkonjic, Hanna Isaksson, Ashok Kumar, Lars Lidgren, Magnus Tägil
Journal: Journal of Controlled Release (2018)
Regulatory Variants of ATF3, CDH17 and FAM71A are Risk Factors for Diisocyanate Induced Occupational Asthma (DA)
Authors: Zana L. Lummus, Banu Kesavalu, Kenneth Kaufman, Jianbo Yao, Matthew T. Weirauch, Leah C. Kottyan, Daniel Miller, André Cartier, Maria-Jesus Cruz, Catherine Lemiere, Xavier Muñoz, Santiago Quirce, Joaquin Sastre, Susan M. Tarlo, David I. Bernstein
Journal: Journal of Allergy and Clinical Immunology (2018)
96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection
Authors: Kosh Agarwal, Maurizia Brunetto, Wai Kay Seto, Young-Suk Lim, Scott Fung, Patrick Marcellin, Sang Hoon Ahn, Namiki Izumi, Wan–Long Chuang, Ho Bae, Manoj Sharma, Harry L.A. Janssen, Calvin Q. Pan, Mustafa Kemal Çelen, Norihiro Furusyo, Dr. Shalimar, Ki Tae Yoon, Huy Trinh, John F. Flaherty, Anuj Gaggar, Audrey H. Lau, Andrea L. Cathcart, Lanjia Lin, Neeru Bhardwaj, Vithika Suri, G. Mani Subramanian, Edward J. Gane, Maria Buti, Henry L.Y. Chan
Journal: Journal of Hepatology (2018)
Enzyme‐Based Glucose Sensor: From Invasive to Wearable Device
Authors: Hyunjae Lee, Yongseok Joseph Hong, Seungmin Baik, Taeghwan Hyeon, Dae‐Hyeong Kim
Journal: Advanced Healthcare Materials (2018)

Abstract Blood glucose concentration is a key indicator of patients' health, particularly for symptoms associated with diabetes mellitus. Because of the large number of diabetic patients, many approaches for glucose measurement have been studied to enable continuous and accurate glucose level monitoring. Among them, electrochemical analysis is prominent because it is simple and quantitative. This technology has been incorporated into commercialized and research‐level devices from simple test strips to wearable devices and implantable systems. Although directly monitoring blood glucose assures accurate information, the invasive needle‐pinching step to collect blood often results in patients (particularly young patients) being reluctant to adopt the process. An implantable glucose sensor may avoid the burden of repeated blood collections, but it is quite invasive and requires periodic replacement of the sensor owing to biofouling and its short lifetime. Therefore, noninvasive methods to estimate blood glucose levels from tears, saliva, interstitial fluid (ISF), and sweat are currently being studied. This review discusses the evolution of enzyme‐based electrochemical glucose sensors, including materials, device structures, fabrication processes, and system engineering. Furthermore, invasive and noninvasive blood glucose monitoring methods using various biofluids or blood are described, highlighting the recent progress in the development of enzyme‐based glucose sensors and their integrated systems.
A Web-Based System for Bayesian Benchmark Dose Estimation
Authors: Kan Shao, Andrew J. Shapiro
Journal: Environmental Health Perspectives (2018)

Benchmark dose (BMD) modeling is an important step in human health risk assessment and is used as the default approach to identify the point of departure for risk assessment. A probabilistic framework for dose-response assessment has been proposed and advocated by various institutions and organizations; therefore, a reliable tool is needed to provide distributional estimates for BMD and other important quantities in dose-response assessment.We developed an online system for Bayesian BMD (BBMD) estimation and compared results from this software with U.S. Environmental Protection Agency's (EPA's) Benchmark Dose Software (BMDS).The system is built on a Bayesian framework featuring the application of Markov chain Monte Carlo (MCMC) sampling for model parameter estimation and BMD calculation, which makes the BBMD system fundamentally different from the currently prevailing BMD software packages. In addition to estimating the traditional BMDs for dichotomous and continuous data, the developed system is also capable of computing model-averaged BMD estimates.A total of 518 dichotomous and 108 continuous data sets extracted from the U.S. EPA's Integrated Risk Information System (IRIS) database (and similar databases) were used as testing data to compare the estimates from the BBMD and BMDS programs. The results suggest that the BBMD system may outperform the BMDS program in a number of aspects, including fewer failed BMD and BMDL calculations and estimates.The BBMD system is a useful alternative tool for estimating BMD with additional functionalities for BMD analysis based on most recent research. Most importantly, the BBMD has the potential to incorporate prior information to make dose-response modeling more reliable and can provide distributional estimates for important quantities in dose-response assessment, which greatly facilitates the current trend for probabilistic risk assessment. https://doi.org/10.1289/EHP1289.