tbuckley/cabot-search huggingface dataset:
Follow-up of patients with uncontrolled asthma: clinical features of asthma patients according to the level of control achieved (the COAS study)
Authors: Rosa Munoz-Cano, Alfons Torrego, Joan Bartra, Jaime Sanchez-Lopez, Rosa Palomino, Cesar Picado, Antonio Valero
Journal: European Respiratory Journal (2017)

Our aim was to study the asthma control achieved in patients with uncontrolled asthma who had received appropriate treatment according to the Global Initiative for Asthma (GINA) 2010 (valid at the time the study was designed), and to analyse the factors associated with a lack of asthma control. This was a multicentre study in routine clinical practice performed in patients with uncontrolled asthma according to GINA 2010. At visit 1, we recorded demographics, asthma characteristics and spirometry. We assessed asthma control using GINA 2010 criteria and the Asthma Control Test (ACT). Treatment was optimised according to GINA 2010. At visit 2, 3 months later, we reassessed spirometry, asthma control and factors associated with failure to achieve control. We recruited 1299 patients with uncontrolled asthma (mean age 46.5±17.3 years, 60.7% women, 25.8% obese). The mean percentage of predicted forced expiratory volume in 1 s was 76.4±12.8% and the mean post-bronchodilator increase was 14.9±6.8%. We observed poor agreement between ACT and GINA 2010 when evaluating asthma control (kappa = −0.151). At visit 2, asthma in 71.2% of patients was still not fully controlled. Patients whose asthma remained uncontrolled were older, had a higher body mass index, greater disease severity, longer disease evolution and worse lung function. After treatment optimisation, most patients did not achieve optimal control according to GINA 2010. Risk factors for failure to achieve asthma control were time of disease evolution, severity, age, weight and lung function impairment (excluded in the GINA 2014).
Return to play criteria after hamstring muscle injury in professional football: a Delphi consensus study
Authors: Mattia Zambaldi, Ian Beasley, Alison Rushton
Journal: British Journal of Sports Medicine (2017)

Background Hamstring muscle injury (HMI) is the most common injury in professional football and has a high re-injury rate. Despite this, there are no validated criteria to support return to play (RTP) decisions. Aim To use the Delphi method to reach expert consensus on RTP criteria after HMI in professional football. Methods All professional football clubs in England (n=92) were invited to participate in a 3-round Delphi study. Round 1 requested a list of criteria used for RTP decisions after HMI. Responses were independently collated by 2 researchers under univocal definitions of RTP criteria. In round 2 participants rated their agreement for each RTP criterion on a 1–5 Likert Scale. In round 3 participants re-rated the criteria that had reached consensus in round 2. Descriptive statistics and Kendall's coefficient of concordance enabled interpretation of consensus. Results Participation rate was limited at 21.7% (n=20), while retention rate was high throughout the 3 rounds (90.0%, 85.0%, 90.0%). Round 1 identified 108 entries with varying definitions that were collated into a list of 14 RTP criteria. Rounds 2 and 3 identified 13 and 12 criteria reaching consensus, respectively. Five domains of RTP assessment were identified: functional performance, strength, flexibility, pain and player's confidence. The highest-rated criteria were in the functional performance domain, with particular importance given to sprint ability. Conclusion This study defined a list of consensually agreed RTP criteria for HMI in professional football. Further work is now required to determine the validity of the identified criteria.
A Phase 3 Pilot Study of Continuous Imatinib Versus Pulsed Imatinib with or without G-CSF in Patients with Chronic Phase CML Who Have Achieved a Complete Cytogenetic Response to Imatinib.
Authors: Nicholas Heaney, Mark Drummond, Jaspal Kaeda, Franck Nicolini, Richard Clark, George Wilson, Pat Shepherd, Jane Tighe, Lorna McLintock, Timothy Hughes, Tessa L. Holyoake
Journal: Blood (2007)
Inflammatory Events in Early Posttransplantation Period Are Associated with the Relapse Kinetics of Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Sung-Yong Kim, Chang-Ki Min, Mi-Jin Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Hee-Je Kim, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Jong-Won Park, Chun-Choo Kim
Journal: Blood (2006)
Evaluation of a Novel Anti-P-Selectin Aptamer ARC5690 On Venous Inflammation Following Acute Venous Thrombosis.
Authors: Jose Antonio Diaz, Patrick A Lester, Jeffrey C Kurz, Shirley K Wrobleski, Angela E Hawley, Robert E Sigler, Thomas W Wakefield, Robert G Schaub, Daniel Myers
Journal: Blood (2009)
Up-regulation of stromal cell-derived factor by il-17 and il-18 via PI3K dependent pathway.
Authors: Inhye Ahn, Ji Hyeon Ju
Journal: Journal of Clinical Oncology (2013)

3046 Background: Stromal cell-derived factor-1 (SDF-1) is a versatile chemotactic cytokine and a sole ligand of CXCR4. SDF-1-CXCR4 axis is the most commonly expressed pathway in cancer cells, and is also responsible for metastasis, homing of stem cell, HIV infection, and autoimmune diseases. Interleukin (IL)-17 plays a key role in the pathogenesis of inflammation by inducing SDF-1 to propagate inflammation and vascular endothelial growth factor to provoke angiogenesis. Recent studies revealed that IL-17 pathway is interwoven with multiple cytokines and downstream pathways. Members of the IL-1β family, including IL-18, have recently gained attention. By measuring SDF-1 production regulated by individual and simultaneous cytokine stimulations, two cytokines were explored to define their effects, their downstream signal transduction pathways, and the impact of their antibodies. Methods: Synovial tissue was obtained from patients with rheumatoid arthritis and their age- and sex-matched controls with osteoarthritis. Fibroblast-like synoviocytes (FLS) were isolated and stimulated with a combination of IL-17 and IL-18 and quantified SDF-1 production with ELISA and their transcripts with RT-PCR. Another subset of FLS were preconditioned with PI3K inhibitor, 100 nM wortmannin, and stimulated with either 5 ng/mL of IL-17, 10 ng/mL of IL-18, or combination of both cytokines. Mann-Whitney test was adopted for statistical analysis. Results: Both IL-17 and IL-18 increased SDF-1 level and its mRNA transcript, not only individually but also synergistically (p &lt;0.05). In the group where PI3K inihibitor was applied, the individual and synergistic promotion of SDF-1 production by IL-17 and IL-18 were inhibited (p&lt;0.05). Concomitant application of anti-IL-17 and anti-IL-18 led to further decline of SDF-1 production (p&lt;0.01). Conclusions: This is the first report of PI3K-dependent synergism between IL-18 and IL-17, and adds a novel perspective of the role of IL-18 in immune regulation. The individual effects of these two cytokines, and their interaction through PI3K, suggest an interrelationship between the IL-1 family and IL-17.
Neutrophil to Lymphocyte Ratio at Diagnosis Is an Independent Prognostic Factor in Diffuse Large B-Cell Lymphoma: Results of a Large Multicenter Study Involving 931 Patients
Authors: Luigi Marcheselli, Alessia Bari, Raffaella Marcheselli, Tamar Tadmor, Samantha Pozzi, Maria Christina Cox, Luca Baldini, Angela Ferrari, Paola Ferri, Massimo Federico, Aaron Polliack, Stefano Sacchi
Journal: Blood (2015)
Pilot study evaluating presence of crown-like structures in high grade endometrial carcinoma.
Authors: Catherine A. Shu, Neil M. Iyengar, Dilip D. Giri, Sarah Chiang, Samantha Williams, Jason A. Konner, Carol Aghajanian, Clifford A. Hudis, Andrew Dannenberg, Vicky Makker
Journal: Journal of Clinical Oncology (2015)

e16504 Background: Obesity is associated with an increased incidence of Type I & II endometrial cancer (EC), decreased recurrence-free interval, and significantly increased mortality rate in EC. Obesity-induced pro-inflammatory state, hyperglycemia, elevated IGF-1, and subsequent mTOR pathway activation are all implicated in endometrial carcinogenesis. Crown-like structures (CLS), consisting of dead or dying adipocytes surrounded by macrophages, are a marker of obesity-associated white adipose tissue (WAT) inflammation (WATi). Their presence in EC has never been examined. Methods: From 2009-2012, women with stage III or IV Grade 3 endometrioid or serous EC who underwent primary surgery at MSKCC and consented to an institutional tissue-banking protocol were identified. WAT was examined in perinodal tissue and omentum and subjected to immunostain with the macrophage marker, CD68, in order to detect CLS by light microscopy. WAT area was measured with NIH Image J in order to provide a standardized measurement. Clinicopathologic data was collected, including body mass index (BMI), and sub-divided into normal (BMI < 25), overweight (BMI 25-30), and obese (BMI ≥ 30) categories. All statistics were descriptive in nature. Results: 28 patients were identified, with a median age of 65.5 (IQR 60.8-72.3) at diagnosis. There were 8 lean (28.6%), 8 overweight (28.6%), and 12 obese (42.9%) patients. There were 14 serous (50.0%), 13 grade 3 endometrioid (46.4%), and 1 mixed serous/grade 3 endometrioid (3.6%) EC. There were 23 stage III (82.1%) and 5 stage IV (17.9%) cancers. Of the 28 patients, only 24 had available perinodal tissue, and 21 had available omental tissue. Two women, both obese, displayed CLS in perinodal WAT. Eight women, 3/5 overweight and 5/8 obese, had CLS in omental WAT. No CLS were observed in normal BMI women. CLS were observed in both serous and endometrioid histologies. Conclusions: For the first time, we have shown that WATi, manifested as CLS, are present in both perinodal and omental WAT of EC patients. In this pilot study, CLS were found more frequently in overweight/obese subjects and appeared to be independent of tumor histology. Prospective studies of the impact of WATi on EC development and progression are planned.
Ex Vivo Expansion of Cord Blood NK Cell Have In Vivo Efficacy Against Leukemia.
Authors: Dongxia Xing, Wendy Fang, William K. Decker, Sufang Li, Simon N. Robinson, Hong Yang, David Steiner, Michael Thomas, Richard E. Champlin, John D. McMannis, Elizabeth J. Shpall, Patrick A. Zweidler-Mckay
Journal: Blood (2007)
The Impact of Antithrombin Deficiency on Women's Reproductive Health Experiences and Healthcare Decision-Making: A Qualitative Patient-Oriented Survey Study
Authors: Ariela L. Marshall, Juliana Perez Botero, John A. Heit, Aneel A. Ashrani, Rajiv K. Pruthi, Ashish V. Chintakuntlawar, Jennifer Guenther, Mrinal M Patnaik
Journal: Blood (2016)
Pembrolizumab, a PD-1 Inhibitor, in Patients with Myelodysplastic Syndrome (MDS) after Failure of Hypomethylating Agent Treatment
Authors: Guillermo Garcia-Manero, Martin S. Tallman, Giovanni Martinelli, Vincent Ribrag, Hui Yang, Arun Balakumaran, Sabine Chlosta, Yayan Zhang, B. Douglas Smith
Journal: Blood (2016)
Abstract P3-04-25: Role of <i>H19</i>, a long non-coding RNA, in development of resistance to endocrine therapy in breast cancer cells
Authors: P Basak, S Chatterjee, V Bhat, H Jin, A Su, LC Murphy, A Raouf
Journal: Cancer Research (2017)

Abstract Introduction: Majority of breast cancer tumors are Estrogen receptor positive (ER+) where antiestrogen therapies (endocrine therapies) are the best therapeutic strategy to treat this type of tumors. However, eventually over 30% of patients will develop resistance to endocrine therapies resulting in disease relapse. We recently showed that the long noncoding RNA, H19, is an estrogen target gene that plays a significant role in estrogen-induced proliferation of the normal and malignant ER+ cells. We therefore hypothesize that H19 expression is also important to the proliferation of endocrine therapy resistant cells. In this study, we examined if estrogen-independent H19 expression is important to the development of endocrine therapy resistance. Objective: The overall objective of this project is to use therapy sensitive (MCF-7) and therapy-resistant (LCC9) breast cancer cells as model systems to examine the role of long non-coding RNA H19 in development and maintenance of resistance to endocrine therapy. Methodology and Results: We examined the expression of H19 in ER+ breast cancer cells (MCF7) that under the selective pressure of fulvesterant (ICI, ER down regulator) acquire resistance to ICI. We observed that while H19 expression was initially decreased as expected, its expression subsequently increased in the ICI-resistant MCF7 cells. Interestingly, H19 knockdown in MCF7 cells significantly decrease their proliferation as determined by Flowcytometry and made them more sensitive to ICI. We also examined H19 expression in the ICI-resistant LCC9 cells and found that ICI treatment increased H19 expression. Interestingly, H19 knockdown in the LCC9 cells decreased their proliferation and surprisingly made them sensitive to ICI treatment. Previous observations indicate that NOTCH4 receptor (NR4) may be involved in endocrine therapy resistance. Interestingly we found that in presence of ICI, NR4 expression is increased and that forced activation of NR4 markedly increases H19 expression in LCC9 cells. Conclusion: Altogether these observations suggest that H19 plays an important role in the development of endocrine therapy resistance and further our understanding of the cellular and molecular mechanisms involved in endocrine therapy resistance. These and similar studies could potentially lead to the development of new therapies to treat therapy resistant tumor cells. Further experiments would reveal if signalling pathways that regulate H19 expression independent of estrogen are useful therapies against endocrine therapy resistant tumors. Citation Format: Basak P, Chatterjee S, Bhat V, Jin H, Su A, Murphy LC, Raouf A. Role of H19, a long non-coding RNA, in development of resistance to endocrine therapy in breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-25.
Screening for Gynecologic Conditions With Pelvic Examination
Authors: Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Michael J. Barry, Karina W. Davidson, Chyke A. Doubeni, John W. Epling, Francisco A. R. García, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, William R. Phillips, Maureen G. Phipps, Michael Silverstein, Melissa Simon, Albert L. Siu, Chien-Wen Tseng
Journal: JAMA (2017)

<h3>Importance</h3> Many conditions that can affect women's health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality. <h3>Objective</h3> To issue a new US Preventive Services Task Force (USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition. <h3>Findings</h3> Overall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women. <h3>Conclusions and Recommendation</h3> The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women. (I statement) This statement does not apply to specific disorders for which the USPSTF already recommends screening (ie, screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia).
Patterns of Clonal Evolution in Ph’-Positive Chronic Myelogenous Leukemia (CML) during Chronic Phase: Overall Incidence, Type, Multiplicity, Development Time, Effect on Subsequent Genetic Instability, Sokal Risk, Type of bcr/abl Transcript and Hematological Evolution.
Authors: Debora Luzi, Lorenzo Falchi, Rita Emili, Ilaria Angeletti, Paolo Prontera, Giovanna Venti, Alessandra Bassetti, Marta Gubbiotti, Vincenzo Capparella, Erminia Gentileschi, Emilio Donti, Anna Marina Liberati
Journal: Blood (2006)
An open-label study of sunitinib (SU) plus exemestane (E) in the first-line treatment of hormone receptor (HR)-positive metastatic breast cancer (MBC)
Authors: P. Ahlgren, M. Thirlwell, R. O’Regan, C. Mormont, L. Levesque, R. Gaspo, M. Woloj, A. Bello, B. Martell, B. Leyland-Jones
Journal: Journal of Clinical Oncology (2009)

e12019 Background: SU, an oral multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET has activity in heavily pretreated pts with MBC. The aromatase inhibitor (AI), E, has proven 1st-line activity that compares favorably with tamoxifen in pts with HR+ BC in the adjuvant setting (Jones et al. 2008). Combining agents that target different signaling pathways may have additive/synergistic activity; combining the AI letrozole with the anti-VEGF agent bevacizumab prolonged progression-free survival to &gt;14 mos as 1st-line therapy for HR+ MBC (Dickler et al. 2008). An open-label, phase I, dose-finding study of first-line SU + E was conducted in HR+ MBC pts. Methods: Eligible pts (postmenopausal; female; ≥18 yrs) had an ECOG PS ≤1, LVEF ≥50% and locally recurrent (unresectable) or MBC. Exclusion criteria included HER2+ BC (unless pt had progressed after trastuzumab) and prior treatment in the metastatic setting. Pts received SU 37.5 mg/d + E 25 mg/d on a continuous daily dosing regimen; if dose-limiting toxicities (DLTs) were experienced by &gt;1/6 pts in the first 8 wks then further pts would be enrolled at SU 25 mg/d + E 25 mg/d. Pharmacokinetic (PK) analyses were performed for each drug and the active SU metabolite SU12662. Results: As of December 2008, enrollment was completed (N=6; mean age 59 ± 11 yrs; 50% of pts had ≥3 metastatic sites). No DLTs were observed and no dose reductions were required throughout the treatment period. An overview of key data is shown below. One death occurred on study (non treatment-related Enterobacter sepsis). No treatment-related G4/5 AEs occurred. PK parameter values determined for SU and E suggested increases in the systemic exposure of both drugs when administered concurrently. Conclusions: These data indicate that SU + E was tolerable with manageable toxicities, with increases in PK parameters and a similar AE profile to that of either single agent alone. This combination should be considered in future clinical trials. [Table: see text] [Table: see text]
Abstract P4-03-15: Joint influence by paracrine adipocyte signals and metabolic conditions on breast cancer
Authors: AH Rosendahl, M Bergqvist, B Lettiero, S Kimbung, S Borgquist
Journal: Cancer Research (2017)

Abstract Background: The growing global population of overweight and obese people represents a pressing public health concern. A higher percentage of body fat is linked to an altered metabolic state and an increased risk of chronic metabolic disorders and cancer. Although, the mechanistic explanations for how obesity affects the development, progression and prognosis of cancer is incompletely mapped. Purpose: To investigate the joint influence by adipocytes and metabolic pressure on breast cancer cell expansion. Experimental Design: In vitro differentiated 3T3-L1 adipocytes were exposed to metabolic glucoselow/high and insulinlow/high pressure in order to mimic normal, pre-diabetic, overt diabetic and late diabetic conditions. Adipocyte-conditioned medium was collected and paracrine effects by adipocyte-derived factors on estrogen receptor (ER)-positive (T47D, MCF-7) and ER-negative (MDA-MB-231) breast cancer cell proliferation, molecular adaptations, and cell motility were subsequently analyzed using sulforhodamine B, Western immunoblotting and migration assays. Results: Under normal metabolic conditions, adipocytes stimulated the growth of ER+ (1.1-2.0-fold; P&amp;lt;0.001) and to a greater extent, ER- breast cancer cells (3.1-fold; P&amp;lt;0.001), compared with controls. The joint effects by adipocyte paracrine signals and higher metabolic pressure (overt or late diabetic conditions), further enhanced the proliferative response in both ER+ and ER- cells (1.3-3.5-fold; P&amp;lt;0.01), compared with controls. Furthermore, adipocyte-derived factors induced morphological changes, protrusion extensions and cell migration in the low invasive T47D cells. Additional acquisition of molecular epithelial-mesenchymal transition features were observed in breast cancer cells following co-culturing with adipocyte-derived factors. Conclusion: These study results support the hypothesis that paracrine signals by adipocytes significantly stimulate the proliferation and induction of a more motile phenotype of human breast cancer cells, which is further enhanced under obesity-associated metabolic conditions. Citation Format: Rosendahl AH, Bergqvist M, Lettiero B, Kimbung S, Borgquist S. Joint influence by paracrine adipocyte signals and metabolic conditions on breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-15.