tbuckley/cabot-search huggingface dataset:
Plus Disease in Retinopathy of Prematurity
Authors: J. Peter Campbell, Jayashree Kalpathy-Cramer, Deniz Erdogmus, Peng Tian, Dharanish Kedarisetti, Chace Moleta, James D. Reynolds, Kelly Hutcheson, Michael J. Shapiro, Michael X. Repka, Philip Ferrone, Kimberly Drenser, Jason Horowitz, Kemal Sonmez, Ryan Swan, Susan Ostmo, Karyn E. Jonas, R.V. Paul Chan, Michael F. Chiang, Michael F. Chiang, Susan Ostmo, Kemal Sonmez, J. Peter Campbell, R.V. Paul Chan, Karyn Jonas, Jason Horowitz, Osode Coki, Cheryl-Ann Eccles, Leora Sarna, Audina Berrocal, Catherin Negron, Kimberly Denser, Kristi Cumming, Tammy Osentoski, Tammy Check, Mary Zajechowski, Thomas Lee, Evan Kruger, Kathryn McGovern, Charles Simmons, Raghu Murthy, Sharon Galvis, Jerome Rotter, Ida Chen, Xiaohui Li, Kent Taylor, Kaye Roll, Jayashree Kalpathy-Cramer, Deniz Erdogmus, Maria Ana Martinez-Castellanos, Samantha Salinas-Longoria, Rafael Romero, Andrea Arriola, Francisco Olguin-Manriquez, Miroslava Meraz-Gutierrez, Carlos M. Dulanto-Reinoso, Cristina Montero-Mendoza
Journal: Ophthalmology (2016)
KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma
Authors: Katherine N. Cahill, Howard R. Katz, Jing Cui, Juying Lai, Shamsah Kazani, Allison Crosby-Thompson, Denise Garofalo, Mario Castro, Nizar Jarjour, Emily DiMango, Serpil Erzurum, Jennifer L. Trevor, Kartik Shenoy, Vernon M. Chinchilli, Michael E. Wechsler, Tanya M. Laidlaw, Joshua A. Boyce, Elliot Israel
Journal: New England Journal of Medicine (2017)

Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma.We conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy.Among the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P=0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P=0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group.In patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01097694 .).
Studies of Tissue Response to Injections of Enzymes
Authors: SAMUEL T. SCHLAMOWITZ, ARTHUR C. DEGRAFF, MAXWELL SCHURERT
Journal: Circulation (1950)

Since 1893, activation of the serum proteolytic enzymes has been accomplished by a variety of methods and agents. Activation of the serum proteolytic enzyme by means of streptokinase, the beta hemolytic streptococcal kinase, has been recently demonstrated. The significant plasma and tissue hexosamine changes, as well as the subcutaneous "nodules" which developed at the injection sites, resemble those observed in the trypsin treated group. Although trypsin and the serum proteolytic enzyme are not identical, they have many characteristics in common.
Safety of Magnetic Resonance Imaging in Patients With Cardiovascular Devices
Authors: Glenn N. Levine, Antoinette S. Gomes, Andrew E. Arai, David A. Bluemke, Scott D. Flamm, Emanuel Kanal, Warren J. Manning, Edward T. Martin, J. Michael Smith, Norbert Wilke, Frank S. Shellock
Journal: Circulation (2007)

Advances in magnetic resonance (MR) imaging over the past 2 decades have led to MR becoming an increasingly attractive imaging modality. With the growing number of patients treated with permanent implanted or temporary cardiovascular devices, it is becoming ever more important to clarify safety issues in regard to the performance of MR examinations in patients with these devices. Extensive, although not complete, ex vivo, animal, and clinical data are available from which to generate recommendations regarding the safe performance of MR examination in patients with cardiovascular devices, as well as to ascertain caveats and contraindications regarding MR examination for such patients. Safe MR imaging involves a careful initial patient screening, accurate determination of the permanent implanted or temporary cardiovascular device and its properties, a thoughtful analysis of the risks and benefits of performing the examination at that time, and, when indicated, appropriate physician management and supervision. This scientific statement is intended to summarize and clarify issues regarding the safety of MR imaging in patients with cardiovascular devices.
Final Report of a Randomized Study of Decitabine Versus Conventional Care (CC) for Maintenance Therapy in Patients with Intermediate and High Risk Acute Myeloid Leukemia (AML) in First or Subsequent Complete Remission (CR)
Authors: Yanis Boumber, Jean-Pierre Issa, Jeffrey L. Jorgensen, Stefan Faderl, Ryan J Castoro, Jane Autry, Guillermo Garcia-Manero, Gautam Borthakur, Elias Jabbour, Zeev Estrov, Jorge E. Cortes, Hagop M. Kantarjian, Farhad Ravandi
Journal: Blood (2011)
Multifunctional Liposomes for Image‐Guided Intratumoral Chemo‐Phototherapy
Authors: Dyego Miranda, Kevin Carter, Dandan Luo, Shuai Shao, Jumin Geng, Changning Li, Upendra Chitgupi, Steven G. Turowski, Nasi Li, G. Ekin Atilla‐Gokcumen, Joseph A. Spernyak, Jonathan F. Lovell
Journal: Advanced Healthcare Materials (2017)

Intratumoral (IT) drug injections reduce systemic toxicity, but delivered volumes and distribution can be inconsistent. To improve IT delivery paradigms, porphyrin-phospholipid (PoP) liposomes are passively loaded with three hydrophilic cargos: sulforhodamine B, a fluorophore; gadolinium-gadopentetic acid, a magnetic resonance (MR) agent; and oxaliplatin, a colorectal cancer chemotherapeutic. Liposome composition is optimized so that cargo is retained in serum and storage, but is released in less than 1 min with exposure to near infrared light. Light-triggered release occurs with PoP-induced photooxidation of unsaturated lipids and all cargos release concurrently. In subcutaneous murine colorectal tumors, drainage of released cargo is delayed when laser treatment occurs 24 h after IT injection, at doses orders of magnitude lower than systemic ones. Delayed light-triggering results in substantial tumor shrinkage relative to controls a week following treatment, although regrowth occurs subsequently. MR imaging reveals that over this time frame, pools of liposomes within the tumor migrate to adjacent regions, possibly leading to altered spatial distribution during triggered drug release. Although further characterization of cargo loading and release is required, this proof-of-principle study suggests that multimodal theranostic IT delivery approaches hold potential to both guide injections and interpret outcomes, in particular when combined with chemo-phototherapy.
Hell on earth? Equatorial peaks of heat, poverty, and aggression
Authors: Evert Van de Vliert, Serge Daan
Journal: Behavioral and Brain Sciences (2017)

Abstract Van Lange et al.'s global CLASH model overemphasizes climatic origins and underemphasizes economic origins of aggression. Our 167-country analysis of latitudinal gradients of heat, poverty, and aggression finds that heat-induced aggression is mediated by poverty and that heat tempers rather than fuels poverty-induced aggression. More importantly, the CLASH model hints at latitudinal, equatorial, and hemispheric upgradings of climato-economic modeling of human behavior.
Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis
Authors: Thomas Pembroke, Marc Deschenes, Bertrand Lebouché, Amine Benmassaoud, Maida Sewitch, Peter Ghali, Philip Wong, Alex Halme, Elise Vuille-Lessard, Costa Pexos, Marina B. Klein, Giada Sebastiani
Journal: Journal of Hepatology (2017)
Abstract P299: Gender-Based Differences in Ozone-Induced Cardiac Dysfunction
Authors: Rajat Sethi, Rama Perepu, Carlos Garcia, David Dostal
Journal: Circulation Research (2011)

Sex related differences have been noted in cardiovascular disease where females have a lower incidence of heart failure, and a higher rate of heart failure survival. On-the-other-hand, some studies have reported increased mortality in women compared with men. Recent data also suggest that women have an increased risk of death due to O 3 air pollution, which is in contrast to reports that short-term variations in gaseous pollutants are associated with an increase in hospitalization for cardiac disease that is not modified by gender. It has been speculated that because of the nature of the photochemical equilibrium of O 3 in the ambient environment and due to other confounding factors epidemiological investigations of the health effects of O 3 may be using O 3 as an exposure surrogate for other oxidants or co-pollutants, some of which may be interfering with response to O 3 . The present study in a controlled exposure protocol tested the hypothesis that female rats compared to male have decreased sensitivity to cardiac injury subsequent to O 3 exposure. Age matched male/female rats were exposed 8 hrs/day for 28 and 56 days to filtered air or 0.8 ppm O 3 . In order to assess the chronic effects to O 3 , in-vivo cardiac function was assessed, 24 hrs after termination of the O 3 exposure. Compared to female rats, LVDP values significantly decreased in O 3 exposed male rats. This enhanced attenuation of cardiac function in male animals was associated with increased myocardial TNF-alpha (TNF-α) levels and decreased myocardial activities of superoxidase dismutase (SOD). These novel findings suggest that decreased attenuation of cardiac function in O 3 exposed females compared to males exposed to similar conditions was associated with decreased inflammatory mediator production and decreased oxidative stress. Identifying the underlying factors for gender based variations in ozone response is very important to recognize at-risk groups who would benefit from preventive strategies. In addition identification of those at risk, their degree of sensitivity will assist with the cost-benefit analysis of “safe” exposure levels in the public health setting. The long-term goal of this study is in guiding regulatory policies for reduced environmental related health costs.
Unusual Sites of Involvement by Hematologic Malignancies
Authors: Magdolna Solti, P. Dileep Kumar, Samir Abraksia
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.19.3991 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11579121 Unusual Sites of Involvement by Hematologic Malignancies Case 2. Meningeal Mycloma With Cord Compression Magdolna SoltixMagdolna SoltiSearch for articles by this author , P. Dileep KumarxP. Dileep KumarSearch for articles by this author , Samir AbraksiaxSamir AbraksiaSearch for articles by this author Show More Huron Hospital and Cancer Center, South Pointe Hospital, Cleveland Clinic Health System, Cleveland, OH https://doi.org/10.1200/JCO.2001.19.19.3991 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Detection of soluble EpCAM in malignant ascites to predict overall survival in patients treated with catumaxomab.
Authors: Andreas Seeber, Ioana Braicu, Gerold Untergasser, Mani Nassir, Normann Steiner, Dominic Fong, Laura Botta, Guenther Gastl, Heidi Fiegl, Alain G Zeimet, Agnieszka Martowicz, Jalid Sehouli, Gilbert Spizzo
Journal: Journal of Clinical Oncology (2014)

e15173 Background: The EpCAM-specific antibody catumaxomab has been approved for intraperitoneal treatment of patients suffering from malignant ascites. New prognostic markers are necessary to select patients that mostly benefit from catumaxomab. This exploratory retrospective analysis was performed on ascites samples to evaluate the predictive role of soluble EpCAM (sEpCAM) in catumaxomab-treated patients. Methods: Sixty-six patients with an available archived ascites sample were included in this study and tested for sEpCAM by an in-house developed and validated ELISA. All probes were sampled before the start of treatment and all patients received at least one catumaxomab infusion. Overall survival and puncture-free survival were compared between sEpCAM-positive and -negative patients. Antibody-dependent cell-mediated cytotoxicity assay (ADCC) was performed to investigate the interaction between sEpCAM and catumaxomab. Results: The ELISA showed a high specificity, accuracy and reproducibility for sEpCAM in ascites as biological matrix. We detected sEpCAM in ascites samples of 9 patients (13.6%). These patients showed a significantly shortened overall survival (p=0.028). The prognostic power of sEpCAM was particularly strong in patients with ovarian cancer (p=0.016). Puncture-free survival was not significantly different between sEpCAM-positive and -negative patients (p=0.18). In vitro analysis with ADCC assay showed a neutralization of catumaxomab due to the blocking effect of sEpCAM. Conclusions: We propose sEpCAM in ascites as a potential predictive marker in cancer patients treated with intraperitoneal catumaxomab. Prospective studies with larger patient cohorts are urgently needed to confirm these findings and exploration of dose-intensified catumaxomab in patients with sEpCAM-positive ascites should be envisaged.
A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma
Authors: Wojciech Jurczak, Moreira Ilidia, Kanaka Setty Govindbabu, Munhoz Eduardo, Echeveste Maria Ascuncion, Pratyush Giri, Castro Nelson, Pereira Juliana, Akria Luiza, Alexeev Sergey, Osmanov Dzhelil, Philippe Pultar, Azzeddine Cherfi, Peijuan Zhu, Jutta Amersdorffer
Journal: Blood (2016)
Abstract 173: Expanded Role for Thrombin/PAR1 Signaling in Cardiac Fibroblast Activation
Authors: Aaron N Snead, Paul A Insel
Journal: Circulation Research (2012)

Cardiac fibrosis is a feature of numerous types of heart disease that lead to disability and death and is characterized by the transformation of cardiac fibroblasts (CFs) to myofibroblasts (myofibs) that synthesize and release large amounts of collagen-rich extracellular matrix (ECM), thereby resulting in reduced cardiac function and eventually heart failure. CFs are the most abundant cell type in the heart and regulate the production of ECM as a normal part of wound repair but disease can result if CFs become overactive, at least in part by increased transformation to myofibs. Cardiac fibrosis can occur spontaneously in advanced age, after acute injury (e.g., myocardial infarction) and in disease states (e.g., diabetes mellitus and heart failure). We sought to identify novel therapeutic targets for cardiac fibrosis by using an unbiased approach (RT-PCR array) to define the most abundantly expressed G protein-coupled receptors (GPCRs) predicted to regulate the CF/myofib transformation. Certain GPCRs, e.g. angiotensin and endothelin receptors, can promote cardiac fibrosis but few others are known to do this. We hypothesized that previously unrecognized GPCRs play an important role in regulating the function of CFs. Using the RT-PCR GPCR array, we found that the protease-activated receptor 1 (PAR1) is the most abundant GPCR in adult rat CFs (rCFs). Thrombin activation of PAR1 in rCFs elevates (with distinct kinetics) the expression of a variety of pro-fibrotic markers, induces morphological changes to the myofib phenotype and stimulates synthesis of collagen, the primary ECM component without affecting cell proliferation. The thrombin-induced initiation of a proliferation-independent pro-fibrotic response in adult rCFs contrasts with effects of thrombin in neonatal rCFs, suggesting a differential wound repair response in the adult versus the still-developing heart. By defining the level of expression of GPCRs in rCFs and revealing an expanded role for PAR1 in the wound repair response of the heart, the data provide a proof-of-principle that our approach can identify novel functional and disease-relevant GPCRs in CFs-- and likely in other cardiovascular cells as well.
Open Label Maintenance Following Milk Oral Immunotherapy (MOIT) for IgE Mediated Cow's Milk Allergy
Authors: S.D. Narisety, J.M. Skripak, P. Steele, R.G. Hamilton, E.C. Matsui, A.W. Burks, R.A. Wood
Journal: Journal of Allergy and Clinical Immunology (2009)
Application of Combination High‐Throughput Phenotypic Screening and Target Identification Methods for the Discovery of Natural Product‐Based Combination Drugs
Authors: Monica Isgut, Mukkavilli Rao, Chunhua Yang, Vangala Subrahmanyam, Padmashree C. G. Rida, Ritu Aneja
Journal: Medicinal Research Reviews (2017)

Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple targets and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural products in drug discovery. Natural products consist of a multitude of constituents that can act on a variety of targets in the body to induce pharmacodynamic responses that may together culminate in an additive or synergistic therapeutic effect. Although natural products cannot be patented, they can be used as starting points in the discovery of potent combination therapeutics. The optimal mix of bioactive ingredients in natural products can be determined via phenotypic screening. The targets and molecular mechanisms of action of these active ingredients can then be determined using chemical proteomics, and by implementing a reverse pharmacokinetics approach. This review article provides evidence supporting the potential benefits of natural product-based combination drugs, and summarizes drug discovery methods that can be applied to this class of drugs.
Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein
Authors: Javier Guenaga, Fernando Garces, Natalia de Val, Robyn L. Stanfield, Viktoriya Dubrovskaya, Brett Higgins, Barbara Carrette, Andrew B. Ward, Ian A. Wilson, Richard T. Wyatt
Journal: Immunity (2017)

Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers and high-resolution clade A, B, and G structures and elicit neutralizing antibodies. However, a high-resolution clade C structure is critical, as this subtype accounts for the majority of HIV infections worldwide, but well-ordered clade C Env trimers are more challenging to produce due to their instability. Based on targeted glycine substitutions in the Env fusion machinery, we defined a general approach that disfavors helical transitions leading to post-fusion conformations, thereby favoring the pre-fusion state. We generated a stabilized, soluble clade C Env (16055 NFL) and determined its crystal structure at 3.9 Å. Its overall conformation is similar to SOSIP.664 and native Env trimers but includes a covalent linker between gp120 and gp41, an engineered 201-433 disulfide bond, and density corresponding to 22 N-glycans. Env-structure-guided design strategies resulted in multiple homogeneous cross-clade immunogens with the potential to advance HIV vaccine development.
Preoperative Chitinase 3-like-1, Galectin-3, and Activin Aplasma levels: A novel diagnostic panel for colorectal cancer.
Authors: Hmc Shantha Kumara, Hiromichi Miyagaki, Sajith A Herath, David Gaita, Xiaohong Yan, Linda Njoh, Vesna Cekic, Nipa Dilip Gandhi, Richard L Whelan
Journal: Journal of Clinical Oncology (2015)

546 Background: Colorectal cancers (CRC) expressChitinase 3-Like-1(Chi3L1), Galectin-3 (Gal-3) and Activin A (Act-A). Chi3L1, indirectly, via IL8 and MCP-1, promotes tumor angiogenesis and progression. Gal-3 promotes tumor cell invasion and angiogenesis while Act-A supports cancer cell migration. This study’s goal was to assess the diagnostic value of plasma levels of Chi3L1, Gal-3 and Act-A, alone or together, for CRC. Methods: PreOp plasma samples were obtained from consenting CRC and benign pathology (BP) patients (pts) undergoing elective resection (IRB approved tissue bank). Plasma levels of Chi3L1, Gal-3 (ng/ml), and Act-A (pg/ml) were determined via ELISA and reported as median + 95% CI. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the CRC diagnostic value of single and multiple plasma protein levels. The Mann-Whitney test was used for statistical analysis (significance p&lt;0.05). Results: A total of 118 CRC (81% colon, 19% rectal) and 42 BP pts (adenoma 31%, diverticulitis 53%, other 16%) were studied. The CRC median plasma protein levels were significantly higher vs. the BP group results [Chi3L1: 120.1, CI: 95.0, 146.6 vs. 36.8, CI; 29.3, 44.4; Gal-3: 12.0, CI: 10.5, 13.3 vs. 7.7, CI: 7.2, 9.9; Act-A: 368.0 CI: 341.0, 421.6 vs. 272.1, CI: 196.0, 327.3 [p&lt;0.001 for all]). The AUC value for the ROC curve for Chi3L1, Gal-3 and Act-A were 0.850, 0.724 and 0.734 respectively with 76%, 52% and 38% specificity. The AUC for the combination of these 3 proteins was 0.890 with 88% specificity. Conclusions: Themedian Chi3L1, Gal-3 and Act-1 values in CRC pts were significantly higher (226%, 55% and 35%) then BP levels. The 3 protein combination had improved AUC and specificity vs single protein results and may have value as a diagnostic panel. A larger study is needed.
Inherited Arrhythmogenic Diseases
Authors: Silvia G. Priori
Journal: Circulation Research (2004)

Twelve years after the identification of the molecular bases of the long-QT syndrome, it is now possible to express some considerations on the impact that genetic findings have had in the understanding of inherited arrhythmogenic diseases. Along with the excitement for the emerging data on genotype/phenotype correlation and for the development of the first recommendations for gene-specific management of patients, it is also important to acknowledge the unexpected complexity that has emerged. The focus of this article is to analyze the elusive aspects of the relationship between genetic defects and clinical manifestations and to propose some research directions that may provide the needed answers to move forward in the understanding of the genetics of heart rhythm abnormalities.
A short course of l-arginine improves exercise capacity and endothelial function in chronic heart failure: A prospective, randomised, double blind trial
Authors: M Yousufuddin, M Flather, W Shamim, Z Yousef, M Marber, M Amrani, N Banner, M Kemp, J Hooper, A J S Coats
Journal: Journal of the American College of Cardiology (2001)