tbuckley/cabot-search huggingface dataset:
S133 The assessment of health related quality of life in interstitial lung disease with the King's brief interstitial lung disease questionnaire (K-BILD)
Authors: A. S. Patel, R. Siegert, K. Brignall, G. Keir, S. Bajwah, S. R. Desai, A. U. Wells, I. J. Higginson, S. S. Birring
Journal: Thorax (2011)

<h3>Introduction</h3> The King9s brief interstitial lung disease questionnaire (K-BILD) is a recently developed and validated 15 item HRQOL questionnaire comprising of 3 health domains (psychological, breathlessness and activities, and chest symptoms) and an overall HRQOL score. We set out to evaluate HRQOL in a large group of patients with interstitial lung diseases (ILD9s) and determine the factors that influence it. <h3>Methods</h3> 219 patients with ILD (60 idiopathic pulmonary fibrosis (IPF), 81 connective tissue associated ILD, 23 idiopathic non-specific interstitial pneumonitis (NSIP), 21 hypersensitivity pneumonitis, 10 organising pneumonia, 24 other) attending ILD clinics at King9s College and Royal Brompton Hospitals completed the K-BILD. The K-BILD Scores range from 0 to 100, with a higher score representing a better HRQOL. Demographic data, immunosuppressant medication, long-term oxygen therapy use, multi-disciplinary team ILD diagnosis and lung function were recorded. <h3>Results</h3> Patients had a mean (SEM) age of 60 (1) years, 75% of patients were Caucasian, 60% were females, mean (SEM) VC% predicted was 80 (24) % and TLCO % predicted was 47 (18)%. HRQOL was impaired in all domains, mean (SEM) scores: psychological 62 (2), breathlessness and activities 43 (2), chest symptoms 67 (2), total 59 (2). There were no significant associations between overall HRQOL and age (r=−0.007) or gender (p=0.13). There was a modest correlation between HRQOL and lung function (Abstract S133 table 1). HRQOL was significantly lower in IPF patients compared to other ILD9s (total score 51 (3) vs 62 (2); p&lt;0.01), those with UIP pattern vs NSIP (total score 51 (3) vs 62 (3); p&lt;0.01) and those prescribed long-term oxygen therapy (total score 38 (4) vs 63 (2); p&lt;0.01). IPF patients prescribed immunosuppressant medication had significantly worse overall HRQOL (48 (4) vs 74 (8); p=0.02). There was no significant difference between CTD-NSIP patients compared with idiopathic NSIP (total score 62 (3) vs 62 (5); p=0.91). <h3>Conclusions</h3> HRQOL is impaired in patients with ILD. The type of ILD, immunosuppressant medication, and lung function all influence HRQOL. This study provides further clinical validation of the K-BILD.
IRF5 promotes the proliferation of human thyroid cancer cells
Authors: Michele Massimino, Paolo Vigneri, Manuela Fallica, Annamaria Fidilio, Alessandra Aloisi, Francesco Frasca, Livia Manzella
Journal: Molecular Cancer (2012)

Abstract Background Interferon Regulatory Factor 5 is a transcription factor that regulates the expression of genes involved in the response to viral infection and in the stimulation of the immune system. Moreover, multiple studies have demonstrated that it negatively regulates cell growth and oncogenesis, favoring cell differentiation and apoptosis. Thyroid carcinoma represents 98% of all thyroid malignancies and has shown a steady increase in incidence in both the USA and western European countries. Findings We investigated the expression, localization and function of IRF5 in thyroid cancer cells and found that it is highly expressed in both primary and immortalized thyroid carcinomas but not in normal thyrocytes. IRF5 levels were variably modulated by Interferon alpha but IRF5 only localized in the cytoplasmic compartment, thus failing to induce p21 expression as previously reported in different cell models. Furthermore, ectopic IRF5 increased both the proliferation rate and the clonogenic potential of malignant thyroid cells, protecting them from the cytotoxic effects of DNA-damaging agents. These results were directly attributable to IRF5, as demonstrated by the reduction in colony-forming ability of thyroid cancer cells after IRF5 silencing. An IRF5-dependent induction of endogenous B-Raf observed in all thyroid cancer cells might contribute to these unexpected effects. Conclusions These findings suggest that, in thyroid malignancies, IRF5 displays tumor-promoting rather than tumor-suppressor activities.
Association of Pain in Knee Osteoarthritis With Distinct Patterns of Synovitis
Authors: B. J. E. de Lange‐Brokaar, A. Ioan‐Facsinay, E. Yusuf, A. W. Visser, H. M. Kroon, G. J. V. M. van Osch, A.‐M. Zuurmond, V. Stojanovic‐Susulic, J. L. Bloem, R. G. H. H. Nelissen, T. W. Huizinga, M. Kloppenburg
Journal: Arthritis & Rheumatology (2014)

To determine possible patterns of synovitis on contrast-enhanced magnetic resonance imaging (CE-MRI) and its relation to pain and severity in patients with radiographic knee osteoarthritis (OA).In total, 86 patients (mean age 62 years, 66% women, median body mass index 29 kg/m(2) ) with symptomatic knee OA (Kellgren/Lawrence radiographic score 3) were included. T1-weighted, gadolinium-chelate-enhanced MRI with fat suppression was used to semiquantitatively score the extent of synovitis at 11 knee sites (total score range 0-22). Self-reported pain was assessed with 3 standardized questionnaires. Principal components analysis (PCA) was used to investigate patterns (the location and severity) of synovitis. Subsequently, these patterns were assessed for associations with pain measures and radiographic severity in adjusted logistic regression models.Synovitis was observed in 86 patients and was found to be generally mild on CE-MRI (median total synovitis score 7, range 0-16). The median pain scores were 53 (range 0-96) on the visual analog scale for pain, 51.4 (range 2.8-97.2) on the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, 35 (range 0-75) on the Intermittent and Constant Osteoarthritis Pain (ICOAP) score for constant pain, and 40.6 (range 0-87.5) on the ICOAP score for intermittent pain. PCA resulted in extraction of 3 components, explaining 53.4% of the variance. Component 1 was characterized by synovitis at 7 sites (mainly medial parapatellar involvement) and was associated with scores on the KOOS pain subscale and the ICOAP constant pain subscale. Component 2 was characterized by synovitis at 4 sites (mainly the site adjacent to the anterior cruciate ligament), but was not associated with pain measures or with radiographic severity. Component 3, characterized by synovitis at 3 sites (mainly at the loose body site), was associated with radiographic severity.Different patterns of synovitis in knee OA were observed. The pattern that included several patellar sites was associated with pain, whereas other patterns showed no association, suggesting that pain perception in patients with knee OA is a localized response.
Interferon lambdas: the next cytokine storm
Authors: C. Kelly, P. Klenerman, E. Barnes
Journal: Gut (2011)

For two decades the scientific community has sought to understand why some people clear hepatitis C virus (HCV) and others do not. Recently, several large genome-wide association studies have identified single nucleotide polymorphisms (SNPs) linked to interferon lambda 3 (IFNλ3) that are associated with the spontaneous resolution and successful treatment of HCV infection. These observations are generating intense research activity; the hope is that IFNλ3 genetic variants may serve as important predictive biomarkers of treatment outcome and offer new insights into the biological pathways involved in viral control. A pharmacogenomic treatment approach for HCV can now be envisaged, with the incorporation of host genetic variants into a predictive treatment algorithm with other factors. The SNPs associated with the clinical outcome of HCV infection are located some distance from the IFNλ3 gene itself, and causal genetic variants have yet to be clearly defined. Locating these causal variants, mapping in detail the IFNλ3 signalling pathways and determining the downstream genetic signature so induced will clarify the role of IFNλ3 in the pathogenesis of HCV. Clinical studies assessing safety and efficacy in the treatment of HCV with exogenous IFNλ3 are currently underway. Early results suggest that IFNλ3 treatment inhibits HCV replication and is associated with a limited side effect profile. However, hepatotoxicity in both healthy volunteers and HCV-infected patients has been described. This review discusses the genetic studies that link IFNλ3 to both the spontaneous resolution and treatment-induced clearance of HCV and the potential impact of this in clinical practice, the biology of IFNλ3 as currently understood and how this may impact on HCV infection, and describes the early studies that assess the role of this cytokine in the treatment of patients with HCV.
Analysis of the storage and secretion of von Willebrand factor in blood outgrowth endothelial cells derived from patients with von Willebrand disease
Authors: Jiong-Wei Wang, Eveline A. M. Bouwens, Maria Carolina Pintao, Jan Voorberg, Huma Safdar, Karine M. Valentijn, Hetty C. de Boer, Koen Mertens, Pieter H. Reitsma, Jeroen Eikenboom
Journal: Blood (2013)
Some lasers are more equal than others
Authors: C.C. Harland
Journal: British Journal of Dermatology (2015)

Journal Article Some lasers are more equal than others Get access C.C. Harland C.C. Harland Department of Dermatology Epsom and St Helier University Hospitals NHS Trust Carshalton Surrey SM5 1AA U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 3, 1 March 2015, Pages 558–559, https://doi.org/10.1111/bjd.13528 Published: 01 March 2015
Randomized Phase III Trial of Retinoic Acid and Arsenic Trioxide Versus Retinoic Acid and Chemotherapy in Patients With Acute Promyelocytic Leukemia: Health-Related Quality-of-Life Outcomes
Authors: Fabio Efficace, Franco Mandelli, Giuseppe Avvisati, Francesco Cottone, Felicetto Ferrara, Eros Di Bona, Giorgina Specchia, Massimo Breccia, Alessandro Levis, Simona Sica, Olimpia Finizio, Maria Grazia Kropp, Giuseppe Fioritoni, Elisa Cerqui, Marco Vignetti, Sergio Amadori, Richard F. Schlenk, Uwe Platzbecker, Francesco Lo-Coco
Journal: Journal of Clinical Oncology (2014)

A randomized clinical trial compared efficacy and toxicity of standard all-trans-retinoic acid (ATRA) plus chemotherapy versus ATRA plus arsenic trioxide in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL). Here, we report health-related quality-of-life (HRQOL) results.HRQOL was a secondary end point of this trial. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 was used to assess HRQOL at end of induction and after consolidation therapy. All analyses were based on 156 patients who received at least one dose of treatment, with groups defined according to randomly assigned treatment. Primary analysis was performed, estimating mean HRQOL score over time and differences between treatment arms using a linear mixed model.Overall, 162 patients age 18 to 70 years were enrolled. Of these, 150 and 142 patients were evaluable for HRQOL after induction therapy and third consolidation course, respectively. Overall compliance with HRQOL forms was 80.1%. The largest difference, favoring patients treated with ATRA plus arsenic trioxide, was found for fatigue severity (mean score difference, -9.3; 95% CI, -17.8 to -0.7; P = .034) at end of induction therapy. This difference was also clinically relevant. HRQOL differences between treatment arms at end of consolidation showed that for several scales, differences between treatment arms were marginal.Overall, current HRQOL findings further support the use of ATRA plus arsenic trioxide as preferred first-line treatment in patients with low- or intermediate-risk APL.
Characteristics of the Frequency Spectrum in the Normal Electrocardiogram and in Subjects Following Myocardial Infarction
Authors: PAUL H. LANGNER, DAVID B. GESELOWITZ
Journal: Circulation Research (1960)

The results of a study of the sealar electrocardiogram, utilizing a wide-band recorder, expanded time scale and a low-pass filter, indicate that a recorder flat to at least 500 c.p.s. is required for faithful reproduction. With a high-pass filter, measurable residual signals are present at a cut-off frequency of 1,000 c.p.s., or higher. Therefore, to record these, an adequate response at 1,000 c.p.s. or more is reqnired. The high frequency energy of the electrocardiographic spectrum arises from the fast deflections contained in the original waveform. These may occur in a single fast deflection, notching, or both. Whereas, in the normal individual, high frequency energy usually arises from a relatively smooth, fast deflection, in abnormals the fast events may occur in conjunction with notching, and other deformities. Judging from the technic used in this experiment, a variable band-pass filter is valuable as an aid for studying the high frequency components of the electrocardiogram and establishing equipment requirements. Measurement of peak-to-peak voltage of residual signals gives partial but lot clear-cut separation of normal and abnormal subjects and would not seem to add to the value of high-fidelity electrocardiography per se in routine clinical diagnosis. It is possible that root mean square readings, reflecting the total energy content, might give a better separation between normal and abnormal subjects than peak-to-peak amplitude alone.
Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study
Authors: John R Teerlink, Cyril P Clarke, Khalil G Saikali, Jacqueline H Lee, Michael M Chen, Rafael D Escandon, Lyndsey Elliott, Rachel Bee, Mohammad Reza Habibzadeh, Jonathan H Goldman, Nelson B Schiller, Fady I Malik, Andrew A Wolff
Journal: The Lancet (2011)
Higher Frequency Phenomena in the Normal Ballistocardiogram
Authors: JOHN N. EDSON, ROBERT DICKES, GERALD H. FLAMM, MICHAEL TOBIN
Journal: Circulation Research (1953)

Physiologic higher frequency phenomena may be demonstrated in ballistocardiograms from normal subjects. These phenomena consist of notches or multiple oscillations on the H-I and K-L segments of the tracings. They may be demonstrated by recording the unfiltered output of an electromagnetic direct-body ballistocardiograph. They become more prominent as the transducer is applied closer to the source of cardiovascular forces, or by passing the output of the transducer through a band pass filter. The time relationship of these oscillations to simultaneously recorded heart sounds suggests their association with the ballistics of the closing heart valves.
Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an Important Prognostic Biomarker in Gliomas
Authors: Marc Sanson, Yannick Marie, Sophie Paris, Ahmed Idbaih, Julien Laffaire, François Ducray, Soufiane El Hallani, Blandine Boisselier, Karima Mokhtari, Khe Hoang-Xuan, Jean-Yves Delattre
Journal: Journal of Clinical Oncology (2009)

Unexpected mutations affecting the isocitrate dehydrogenase (IDH1) gene at codon 132 have been found in 12% of glioblastomas.IDH1 codon 132 sequencing was performed in a series of 404 patients with glioma (100 grade 2, 121 grade 3, and 183 grade 4 gliomas) and correlated with histology, genomic profile, methylguanyl methyltransferase (MGMT) promoter methylation status, and outcome.A total of 155 codon 132 mutations were found, of which 131 were Arg132His (88.5%). The IDH1 mutation was inversely correlated with grade, affecting 77% of grade 2, 55% of grade 3, and 6% of grade 4 gliomas (P < 10(-15)). The IDH1 mutation was tightly associated with a 1p19q codeleted genotype (P < 10(-14)) and an MGMT methylated status (P < .001) but mutually exclusive with EGFR amplification (P < 10(-15)) and loss of chromosome 10 (P < 10(-15)). The presence (v absence) of IDH1 mutation was associated with a better outcome in grade 2 (150.9 v 60.1 months, respectively; P = .01), grade 3 (81.1 v 19.4 months, respectively; P < .001), and grade 4 gliomas (27.4 v 14 months, respectively; P < .01). After adjustment for grade, age, MGMT status, genomic profile, and treatment, multivariate analysis confirmed that IDH1 mutation was an independent favorable prognostic marker (hazard ratio = 0.297; 95% CI, 0.157 to 0.564, P = .00021).This study indicates that IDH1 codon 132 mutation is closely linked to the genomic profile of the tumor and constitutes an important prognostic marker in grade 2 to 4 gliomas.
Genetic variation in chitinase 3-like 1 (CHI3L1) contributes to asthma severity and airway expression of YKL-40
Authors: Jose L. Gomez, Gina M. Crisafi, Carole T. Holm, Deborah A. Meyers, Gregory A. Hawkins, Eugene R. Bleecker, Nizar Jarjour, Lauren Cohn, Geoffrey L. Chupp
Journal: Journal of Allergy and Clinical Immunology (2015)
β-Arrestin-1 Drives Endothelin-1–Mediated Podocyte Activation and Sustains Renal Injury
Authors: Simona Buelli, Laura Rosanò, Elena Gagliardini, Daniela Corna, Lorena Longaretti, Anna Pezzotta, Luca Perico, Sara Conti, Paola Rizzo, Rubina Novelli, Marina Morigi, Carlamaria Zoja, Giuseppe Remuzzi, Anna Bagnato, Ariela Benigni
Journal: Journal of the American Society of Nephrology (2013)

Activation of endothelin-A receptor (ET(A)R) by endothelin-1 (ET-1) drives epithelial-to-mesenchymal transition in ovarian tumor cells through β-arrestin signaling. Here, we investigated whether this pathogenetic pathway could affect podocyte phenotype in proliferative glomerular disorders. In cultured mouse podocytes, ET-1 caused loss of the podocyte differentiation marker synaptopodin and acquisition of the mesenchymal marker α-smooth muscle actin. ET-1 promoted podocyte migration via ET(A)R activation and increased β-arrestin-1 expression. Activated ET(A)R recruited β-arrestin-1 to form a trimeric complex with Src leading to epithelial growth factor receptor (EGFR) transactivation and β-catenin phosphorylation, which promoted gene transcription of Snail. Increased Snail expression fostered ET-1-induced migration as confirmed by Snail knockdown experiments. Silencing of β-arrestin-1 prevented podocyte phenotypic changes and motility and inhibited ET(A)R-driven signaling. In vitro findings were confirmed in doxorubicin (Adriamycin)-induced nephropathy. Mice receiving Adriamycin developed renal injury with loss of podocytes and hyperplastic lesion formation; β-arrestin-1 expression increased in visceral podocytes and in podocytes entrapped in pseudo-crescents. Administration of the selective ET(A)R antagonist sitaxsentan prevented podocyte loss, formation of the hyperplastic lesions, and normalized expression of glomerular β-arrestin-1 and Snail. Increased β-arrestin-1 levels in podocytes retrieved from crescents of patients with proliferative glomerulopathies confirmed the translational relevance of these findings and suggest the therapeutic potential of ET(A)R antagonism for a group of diseases still needing a specific treatment.
Profiling Microdissected Epithelium and Stroma to Model Genomic Signatures for Cervical Carcinogenesis Accommodating for Covariates
Authors: David Gius, Margo C. Funk, Eric Y. Chuang, Sheng Feng, Phyllis C. Huettner, Loan Nguyen, C. Matthew Bradbury, Mark Mishra, Shuping Gao, Barbara M. Buttin, David E. Cohn, Matthew A. Powell, Neil S. Horowitz, Bradford P. Whitcomb, Janet S. Rader
Journal: Cancer Research (2007)

Abstract This study is the first comprehensive, integrated approach to examine grade-specific changes in gene expression along the entire neoplastic spectrum of cervical intraepithelial neoplasia (CIN) in the process of cervical carcinogenesis. This was accomplished by identifying gene expression signatures of disease progression using cDNA microarrays to analyze RNA from laser-captured microdissected epithelium and underlying stroma from normal cervix, graded CINs, cancer, and patient-matched normal cervical tissues. A separate set of samples were subsequently validated using a linear mixed model that is ideal to control for interpatient gene expression profile variation, such as age and race. These validated genes were ultimately used to propose a genomically based model of the early events in cervical neoplastic transformation. In this model, the CIN 1 transition coincides with a proproliferative/immunosuppression gene signature in the epithelium that probably represents the epithelial response to human papillomavirus infection. The CIN 2 transition coincides with a proangiogenic signature, suggesting a cooperative signaling interaction between stroma and tumor cells. Finally, the CIN 3 and squamous cell carcinoma antigen transition coincide with a proinvasive gene signature that may be a response to epithelial tumor cell overcrowding. This work strongly suggests that premalignant cells experience a series of microenvironmental stresses at the epithelium/stroma cell interface that must be overcome to progress into a transformed phenotype and identifies the order of these events in vivo and their association with specific CIN transitions. [Cancer Res 2007;67(15):7113–23]
Increased 24-h Energy Expenditure in Type 2 Diabetes
Authors: Christian Bitz, Søren Toubro, Thomas M. Larsen, Helle Harder, Kirsten L. Rennie, Susan A. Jebb, Arne Astrup
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to determine whether overweight and obese individuals with type 2 diabetes have higher basal and 24-h energy expenditure compared with healthy control subjects before and after adjustment for body composition, spontaneous physical activity (SPA), sex, and age. RESEARCH DESIGN AND METHODS—Data from 31 subjects with type 2 diabetes and 61 nondiabetic control subjects were analyzed. The 24-h energy expenditure, basal metabolic rate (BMR), and sleeping energy expenditure (EEsleep) between 1:00 a.m. and 6:00 a.m. were measured in whole-body respiratory chambers. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). RESULTS—No significant differences in unadjusted EEsleep, BMR, and 24-h energy expenditure were observed between the type 2 diabetic group and the control group. After adjustment for fat-free mass (FFM), fat mass, SPA, sex, and age, EEsleep and BMR were, respectively, 7.7 and 6.9% higher in the type 2 diabetic group compared with the control group. This was equivalent to 144 ± 40 kcal/day (P = 0.001) and 139 ± 61 kcal/day (P = 0.026), respectively. Adjusted 24-h energy expenditure was 6.5% higher in the type 2 diabetic group compared with the nondiabetic control subjects (2,679 ± 37 vs. 2,515 ± 23 kcal/day, P = 0.002). In multiple regression analyses, FFM, fat mass, SPA, and diabetes status were all significant determinants of EEsleep and 24-h energy expenditure, explaining 83 and 81% of the variation, respectively. CONCLUSIONS—This study confirms reports in Pima Indians that basal and 24-h energy expenditure adjusted for body composition, SPA, sex, and age are higher in individuals with type 2 diabetes compared with nondiabetic control subjects and may be even more pronounced in Caucasians.