tbuckley/cabot-search huggingface dataset:
ATP and cough reflex hypersensitivity: a confusion of goals?
Authors: Maria G. Belvisi, Jaclyn A. Smith
Journal: European Respiratory Journal (2017)

The term "cough hypersensitivity syndrome" (CHS) has been proposed by a European Respiratory Society Task Force as a clinical syndrome characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in patients presenting with chronic cough [1]. There are no agreed clinical criteria defining this syndrome or diagnostic tests to confirm its presence. However, it is often assumed that this syndrome must be linked to a hypersensitivity of the vagal afferent nerves and an intrinsic defect in the nerves themselves, which may not be the case [2]. The paper by Fowles et al . [3] describes a tussive challenge study with ATP and AMP in healthy volunteers and unselected patients attending a cough clinic, demonstrating the greater potency of ATP versus AMP, and that chronic cough patients had a greater cough response at lower concentrations of ATP. The degree of hypersensitivity demonstrated in chronic cough patients did not appear to be greater in magnitude than seen previously with capsaicin challenge (the only other example where an intervention against a specific challenge agent has been tested) [4–6]. However, a TRPV1 receptor antagonist did not impact on cough in this patient group despite a greater sensitivity to capsaicin challenge [6]. The authors have concluded, therefore, that 1) a similar shift in sensitivity in the ATP challenge does not explain the efficacy of the P2X3 antagonist (AF-219/MK-7264) and that 2) it is not a peripheral response to ATP that underlies the increased coughing in these patients. The term "cough hypersensitivity syndrome" describes exaggerated cough but not necessarily the mechanisms involved <http://ow.ly/Wk0n30bWmAy>
Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank
Authors: Donald M. Lyall, Carlos Celis-Morales, Joey Ward, Stamatina Iliodromiti, Jana J. Anderson, Jason M. R. Gill, Daniel J. Smith, Uduakobong Efanga Ntuk, Daniel F. Mackay, Michael V. Holmes, Naveed Sattar, Jill P. Pell
Journal: JAMA Cardiology (2017)

Higher body mass index (BMI) is a risk factor for cardiometabolic disease; however, the underlying causal associations remain unclear.To use UK Biobank data to report causal estimates of the association between BMI and cardiometabolic disease outcomes and traits, such as pulse rate, using mendelian randomization.Cross-sectional baseline data from a population-based cohort study including 119 859 UK Biobank participants with complete phenotypic (medical and sociodemographic) and genetic data. Participants attended 1 of 22 assessment centers across the United Kingdom between 2006 and 2010. The present study was conducted from May 1 to July 11, 2016.Prevalence of hypertension, coronary heart disease, and type 2 diabetes were determined at assessment, based on self-report. Blood pressure was measured clinically. Participants self-reported sociodemographic information pertaining to relevant confounders. A polygenic risk score comprising 93 single-nucleotide polymorphisms associated with BMI from previous genome-wide association studies was constructed, and the genetic risk score was applied to derive causal estimates using a mendelian randomization approach.Of the 119 859 individuals included in the study, 56 816 (47.4%) were men; mean (SD) age was 56.87 (7.93) years. Mendelian randomization analysis showed significant positive associations between genetically instrumented higher BMI and risk of hypertension (odds ratio [OR] per 1-SD higher BMI, 1.64; 95% CI, 1.48-1.83; P = 1.1 × 10-19), coronary heart disease (OR, 1.35; 95% CI, 1.09-1.69; P = .007) and type 2 diabetes (OR, 2.53; 95% CI, 2.04-3.13; P = 1.5 × 10-17), as well as systolic blood pressure (β = 1.65 mm Hg; 95% CI, 0.78-2.52 mm Hg; P = 2.0 × 10-04) and diastolic blood pressure (β = 1.37 mm Hg; 95% CI, 0.88-1.85 mm Hg; P = 3.6 × 10-08). These associations were independent of age, sex, Townsend deprivation scores, alcohol intake, and smoking history.The results of this study add to the burgeoning evidence of an association between higher BMI and increased risk of cardiometabolic diseases. This finding has relevance for public health policies in many countries with increasing obesity levels.
Postlumpectomy loco-regional breast cancer therapy with liposomal therapeutic agents: Retention and distribution in nude rats
Authors: S. Li, B. Goins, W. T. Phillips, M. Saenz, P. Otto, A. Bao
Journal: Journal of Clinical Oncology (2009)

e11562 Background: Post-lumpectomy loco-regional radiation therapy, such as brachytherapy, has been shown to decrease breast cancer recurrence and increase patient survival. Limitations of current brachytherapy are the relatively high radiation absorbed dose delivered to normal breast and the inability to treat potentially involved lymph nodes. Locally administered liposomes are being investigated for delivery of drugs and therapeutic radionuclides. We propose a new post-lumpectomy loco-regional therapy with liposome-carried therapeutic agents. To investigate, radiolabeled liposomes were injected into the surgical cavity of a nude rat model one day following surgical removal of the breast tumor, and in vivo retention and distribution were monitored with nuclear imaging and post- mortem dissection. Methods: Six liposome formulations containing 0.2% molar ratio Rhodamine B-lipid and cationic, neutral, or anionic surface charges were manufactured at diameters of 400 or 100 nm and characterized. Breast cancer xenograft model in female nude rats was set up by inoculating MDA-MB-231 cells into the fat pad of the left breast of each rat. When tumor volumes reached 1.9 cm 3 on average, the majority of each tumor was surgically removed, leaving ∼0.05 cm 3 tumor tissue in the cavity. Then, each rat (3–4 rats/group) was intracavitarily injected with 0.5 ml of 99m Tc-liposomes (4 mCi., 30 mg total lipids/kg body weight). In vivo distribution of 99m Tc-activity was measured with planar gamma camera and SPECT imaging at various times. Post-mortem stereo fluorescent images of surgical cavity and the surrounding lymph nodes at 44 h were acquired. Results: All 99m Tc-liposome formulations had approximately ≥ 50% retention in the surgical cavity at 44 h after injection. 99m Tc-anionic liposomes of 100 nm diameter had an optimal lymph node targeting with ∼6%/g tissue in the surrounding lymph nodes at 44 h. Fluorescence imaging of the liposomes clearly showed their clearance through surrounding lymphatics and retention in lymph nodes. Conclusions: Anionic liposomes of 100 nm diameter are promising carriers for the simultaneous treatment of the surgical cavity and its draining lymph nodes. No significant financial relationships to disclose.
Characterization of germline and tumor genomic profile in unselected young black breast cancer patients.
Authors: Tuya Pal, Deborah Cragun, Xuefeng Wang, Sean J. Yoder, Tania MESA, Marilin Rosa, Ann Tezak, Anne Weidner, Susan Thomas Vadaparampil, Catherine Phelan
Journal: Journal of Clinical Oncology (2017)

e13090 Background: Young black women bear a disproportionate burden of breast cancer (BC), yet there is limited characterization of these cancers based on BRCA1 and BRCA2 ( BRCA) status and tumor genomics. In this pilot study, we characterized: tumor and clinical characteristics based on BRCA carrier status and overlap of basal-like (BL) and triple negative (TN) BC. Methods: A population-based sample of 481 black women diagnosed with invasive BC &lt; age 50 were recruited through the Florida Cancer Registry (FCR). BRCA status was determined based on germline testing. TN status was determined based on pathology reports and FCR data. Among a subset of 90 participants, gene expression profiling (GEP) was conducted on tumor samples through PAM50 analyses to classify intrinsic subtypes and risk of recurrence (ROR) scores. Results: Mean age at BC diagnosis was 41.9 (range: 25-50) and mean ROR score was 49.6 (range: 8.7-80.7). Participants included 7 BRCA1 carriers, 5 BRCA2 carriers, 67 non-carriers (NC), and 11 with no confirmed testing. Of 46 BL tumors, 33 were TN (71.7%) constituting 94.3% of TN tumors (the remaining 5.7% were Luminal A). All BRCA1 carriers had BL tumors, of which 5 were TN. Sensitivity, positive predictive value, and negative predictive value in identifying BRCA1 carrier was higher based on BL compared to TN status (Table 1). BRCA2-associated tumors included 3 Luminal A, 1 Luminal B, and 1 BL. Mean ROR score was highest among BRCA1 carriers (57.7), followed by NC (50.5) and BRCA2 carriers (41.5). Conclusions: Study findings suggest BL status predicted BRCA1 positivity better than TN status. BRCA2- (compared to BRCA1-) associated tumors were more heterogeneous with over half being Luminal A, which may explain the lower ROR among BRCA2 carriers. Additional follow-up and expansion of this cohort with collection of clinical outcomes will be useful in assessing the predictive utility of ROR scores among young black women with BC. [Table: see text]
Third Party CMV-Specific Cytotoxic T Cells for Treatment of Antiviral Resistant CMV Infection after Hematopoietic Stem Cell Transplant
Authors: Susan Prockop, Ekaterina Doubrovina, Aisha N Hasan, Parastoo B Dahi, Sergio Giralt, Guenther Koehne, Nancy A. Kernan, Esperanza B Papadopoulos, Rachel Lehrman, Irene Rodriguez-Sanchez, Richard J. O'Reilly
Journal: Blood (2016)
PD-1+ Polyfunctional T Cells Dominate the Periphery after Tumor-Infiltrating Lymphocyte Therapy for Cancer
Authors: Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Barbara Szomolay, Sascha Ott, Garry Dolton, Rikke Lyngaa, Sine Reker Hadrup, Andrew K. Sewell, Inge Marie Svane
Journal: Clinical Cancer Research (2017)

Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TIL) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs 1 month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here, we studied the dynamics of bulk tumor-reactive CD8+ T-cell populations in patients with metastatic melanoma following treatment with TILs.Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8+ T cells contained in serial blood samples of 16 patients treated with TILs.Results: Polyfunctional tumor-reactive CD8+ T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD-1, and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8+ T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year after infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8+ T cells, further analyses showed that CD8+ T cells specific for defined tumor antigens had similar differentiation status.Conclusions: We demonstrated that tumor-reactive CD8+ T-cell subsets that persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype, and express high levels of PD-1. These partially differentiated PD-1+ polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2-mediated inhibition. Clin Cancer Res; 23(19); 5779-88. ©2017 AACR.
Features of the metabolic syndrome and survival after a diagnosis of breast cancer in the Women’s Health Initiative (WHI).
Authors: Jennifer Lynn Beebe-Dimmer, Theresa Hastert, Daniel Silbiger, Julie Ruterbusch, Elizabeth Cespedes, Rowan T. Chlebowski, Jo L Freudenheim, JoAnn E Manson, Marian Neuhouser, Gloria Ho, Marcia L. Stefanick, Howard D. Strickler, Bette Jane Caan, Michael S. Simon
Journal: Journal of Clinical Oncology (2016)

1517 Background: Metabolic Syndrome (MetS) refers to a cluster of conditions typically associated with cardiovascular disease. Evidence suggests that MetS is associated with an increased risk for several tumors, including breast cancer, however few studies have evaluated the relationship between MetS with outcomes after a breast cancer diagnosis. Methods: We evaluated the relationship between MetS and both breast cancer-specific and overall mortality among women with invasive breast cancer in the WHI Observational Study (OS). Individual MetS features measured prior to diagnosis included waist circumference and blood pressure, self-reported history of high-cholesterol and diabetes. MetS was defined as having ≥ 3 of 4 individual features, modified from Adult Treatment Panel III criteria to accommodate available data. Eligible women were followed until date of death or last follow-up. Cox proportional hazards models were used to estimate hazard ratios for the association between each individual feature and MetS with both breast cancer-specific and overall survival. Results: 4,347 eligible women with breast cancer were followed for an average of 9.9 years, with 956 deaths including 303 due to breast cancer. We found higher all-cause, but not breast cancer-specific mortality among breast cancer patients with MetS (HR = 1.69, 95% CI = 1.30 – 2.21), with a significant trend of higher risk with additional MetS features (p-trend < 0.001). Abdominal adiposity was associated with both increased overall and breast cancer-specific mortality (HR = 1.31, 95% CI = 1.14-1.50 and HR = 1.27, 95% CI = 1.00-1.61, respectively). While the prevalence of MetS was higher in African American women (15%) compared to white women (4%) with breast cancer, there was inadequate power to determine if racial differences exist between MetS and survival. Conclusions: MetS was associated with overall, but not breast cancer-specific survival among women participating in the WHI OS, while abdominal obesity was associated with both all cause and breast cancer-specific mortality. Further study is necessary to determine if there are racial differences in disease-specific mortality associated with MetS in women with breast cancer.
Dose finding phase Ib study of FOLFOXIRI plus ramucirumab as first-line therapy for patients with metastatic colorectal cancer: The initial safety analysis
Authors: Hironaga Satake, Yosuke Kito, Hiroya Taniguchi, Yoshiki Horie, Takeshi Yamada, Taito Esaki, Tadamichi Denda, Keita Mori, Kentaro Yamazaki
Journal: Annals of Oncology (2017)
Combined pulmonary fibrosis and emphysema: bad and ugly all the same?
Authors: Vincent Cottin
Journal: European Respiratory Journal (2017)

Emphysema is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF) [1] and interstitial lung disease (ILD) associated with rheumatoid arthritis [2], conditions linked to tobacco smoking [3]. The combination of pulmonary fibrosis and emphysema (CPFE) has been suggested to be a syndrome [4, 5], based on distinctive clinical, radiological, functional and outcome features [6]. Indeed, patients with CPFE reproducibly present with a distinct functional profile consisting of relative preservation of lung volumes and greater reduction in diffusing capacity of the lung for carbon monoxide ( D LCO) [4]. In a pioneering study, Wells et al. [7] showed that patients with IPF and emphysema had higher lung volumes by 5–10% and lower D LCO by ∼15% as compared to subjects with IPF alone, after adjustment for the extent of ILD. Patients with CPFE have the same prognosis as those with IPF, despite having generally less extensive fibrosis <http://ow.ly/hxSe30c43um>
Adipose‐derived exosomal MicroRNAs orchestrate gene regulation in the liver: Is this the missing link in nonalcoholic fatty liver disease?
Authors: Hannelie Korf, Schalk van der Merwe
Journal: Hepatology (2017)

1Laboratory of Hepatology, Department of Clinical and Experimental MedicineKULeuvenLeuvenBelgium 2Department of Gastroenterology and HepatologyUZLeuvenLeuvenBelgium
Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children (Retracted article. See vol 375, pg 445, 2010)
Authors: AJ Wakefield, SH Murch, A Anthony, J Linnell, DM Casson, M Malik, M Berelowitz, AP Dhillon, MA Thomson, P Harvey, A Valentine, SE Davies, JA Walker-Smith
Journal: The Lancet (1998)
Abstract P328: β-Blockers Can Enhance Short-Term Receptor Sensitivity in Silico and in Vitro
Authors: Robert Amanfu, Jeffrey Saucerman
Journal: Circulation Research (2011)

A key feature of heart failure is the chronic elevation of circulating catecholamines which desensitizes the β-adrenergic receptor signaling pathway, rendering patients incapable of increasing cardiac output in response to acute stress (eg. exercise). β-adrenergic receptor blockers (β-blockers) are commonly used to treat this condition, but precisely how they work is still controversial and poorly understood. Two opposing theories are that β-blockers work by 1) blocking the harmful consequences of chronic signaling or 2) paradoxically increasing receptor sensitivity. To investigate whether β-blockers function by increasing receptor sensitivity, we extended a published computational model of the β 1 -adrenergic receptor signaling pathway developed in our lab by using a ternary complex receptor module. This receptor model includes the spontaneous switching between the active and inactive conformations of the receptor that is crucial for accurate representation of β-blockers. Parameter values were determined from literature to model 11 agonists and 10 β-blockers. The new receptor model was validated against ligand binding studies and adenylyl cyclase assays from literature. Chronic and acute stresses were modeled as low and high (100X greater) concentrations of the agonist isoproterenol. Simulations indicate that when the β-blocker propranolol is present during chronic stress, cAMP levels are increased upon application of an acute stress, elevating intracellular calcium levels and contractility. This suggests that in addition to blocking the harmful consequences of chronic signaling, β-blockers may sensitize the response to acute stress. Preliminary data from calcium imaging experiments in isolated cardiac ventricular cells confirm this prediction. Simulations with a range of commonly used β-blockers indicate that individual drugs differ significantly in their ability to enhance receptor sensitivity. In addition, simulation of the Gly389Arg polymorphism suggests that the Arg389 variant has reduced sensitization to acute stress in the presence of propranolol. These simulations are a first step towards evaluating personalized β-blocker therapies with computational models.
Life expectancy 20 years after cisplatin-based treatment for testicular cancer (TC).
Authors: Sjoukje Lubberts, Lara M. Kruyt, Lars Christiaan Steggink, Gerrie Steursma, Janine Nuver, Sjoukje Oosting, Robert J. van Ginkel, Igle J. de Jong, Christine Eulenburg, Joop D. Lefrandt, Coby Meijer, Wim J. Sluiter, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2017)

4550 Background: Four decades have passed since the introduction of cisplatin-based chemotherapy for metastatic TC, providing the opportunity to evaluate very long-term survival. Although 80-90% of the patients are cured, the effect of treatment on residual life span is unknown. Aim of the study was to investigate life expectancy after TC treatment: from prolonging survival after cancer diagnosis, focus shifts to regaining a normal residual life span. Methods: Patients with metastatic TC treated with cisplatin-based chemotherapy &gt; 20 years ago (1977 - 1996) at the University Medical Center Groningen were included. Survival status and cause of death were obtained from medical records, Netherlands Cancer Registry and general practitioners. Events were defined as death due to any cause (overall mortality) and death due to TC or TC treatment complications (TC specific mortality). Standardized mortality ratios (SMR) were calculated as ratio between observed and expected deaths, derived from the age-matched nationwide male population (Dutch Central Office of Statistics). SMRs were calculated for overall mortality, non TC specific mortality (censoring death from TC or treatment-related complications), mortality from cardiovascular disease (censoring death from other causes than cardiovascular disease (ICD-10 I0-I99)) and mortality from secondary malignancies (censoring death from other causes than secondary malignancies (ICD-10 C0-C99 excluding C62: TC)). Results: We included 321 metastatic TC patients with a median age of 28 years (range 16 - 64) at start of chemotherapy. After a median follow-up of 25 years (range 0 - 38) 106 patients died (33%). SMR for overall mortality was 4.0 (95% CI 3.6 - 4.4) and for non TC specific mortality 1.5 (95% CI 1.1 - 1.9). SMR for secondary malignancies was 1.7 (95% CI 1.0 - 2.2) and for cardiovascular diseases 1.5 (95% CI 0.7 - 2.2). Median age at death was 5-10 years lower in TC patients than expected. Conclusions: Twenty years after cisplatin-based chemotherapy, TC patients have a 50% increased risk of dying from non TC causes compared to the general population. These findings suggest that cisplatin-based treatment for TC comes at the expense of about 7.5 life years and induces early aging.
Failure to rescue in living donor liver transplantation: Patterns and predictors
Authors: Abu Bakar Hafeez Bhatti, Faisal Saud Dar, Ammal Imran Qureshi, Nusrat Yar Khan, Haseeb Haider Zia, Eitzaz ud din Khan, Nasir Ayub Khan, Mohammad Salih, Najmul Hassan Shah
Journal: International Journal of Surgery (2017)
"ERS/ESTS CLINICAL GUIDELINES ON FITNESS FOR RADICAL THERAPY IN LUNG CANCER PATIENTS (SURGERY AND CHEMO-RADIOTHERAPY)". A. BRUNELLI, A. CHARLOUX, C.T. BOLLIGER, G. ROCCO, J-P. SCULIER, G. VARELA, M. LICKER, M.K. FERGUSON, C. FAIVRE-FINN, R.M. HUBER, E.M. CLINI, T. WIN, D. DE RUYSSCHER AND L. GOLDMAN ON BEHALF OF THE EUROPEAN RESPIRATORY SOCIETY AND EUROPEAN SOCIETY OF THORACIC SURGEONS JOINT TASK FORCE ON FITNESS FOR RADICAL THERAPY. EUR RESPIR J 2009; 34: 17-41.
Authors: G Sculier, M Varela, M Licker, C Ferguson, R Faivre-Finn, E Huber, T Clini, D Win, L De
Journal: European Respiratory Journal (2009)

Unfortunately, an incorrect value was given in the second paragraph of the Exercise tests section of the above manuscript.The penultimate sentence should have read as follows: ''Between both values, post-operative FEV1 and DL,CO were estimated and, in those cases having either one .40%and ppo-VO 2 ,peak .35%and .10mL?kg -1 ?min -1 , surgical resection was performed.''Additionally, in figure 2 of the above manuscript, two of the values relating to exercise testing peak oxygen consumption (VO 2 ) were presented incorrectly.