tbuckley/cabot-search huggingface dataset:
External validation of the REVEAL risk score calculator for PAH survival: A French pulmonary hypertension network analysis
Authors: Olivier Sitbon, Marc Humbert, Gérald Simonneau, Jean-Christophe Lemarie, Dave Miller, Erwan Muros Le Rouzic, Virginie Gressin, David Badesch, Raymond Benza, C. Gregory Elliott, Adaani Frost, Michael McGoon
Journal: European Respiratory Journal (2012)

Introduction:  The French Pulmonary Hypertension Network (FPHN) and the Registry to EValuate Early And Long-term Pulmonary Arterial Hypertension (PAH) Disease Management (REVEAL) have recently developed predictive models for survival in patients with PAH.   Aims and objectives: The  REVEAL risk score calculator was assessed in a FPHN cohort to evaluate its generalizability in a different PAH population.   Methods:  French validation cohort was built to approximate the inclusion/exclusion criteria originally defined by REVEAL. For each patient, the risk score was evaluated using most recent assessment of risk at any clinic visit from November 2006 or later.   Results:  The French validation cohort had 1738 patients (pts) with group 1 PAH, mean ± standard deviation 6-min walk distance of 356 ± 130 m and 53% pts in functional class III. Observed 1-yr survival for patients with risk scores of 1-7, 8, 9, 10-11, or 12+ were 96.4%, 88.6%, 86.4%, 78.7%, and 62.1%, respectively (Figure) falling close to the predicted risk for each of these 5 pre-specified risk strata. The c-index for the risk calculator was .729.  Predicted versus observed 1-year survival in FPHN.   Conclusion:  The REVEAL risk score calculator was accurate and well calibrated in the FPHN, suggesting its prognostic generalizability in a different PAH population and in everyday clinical practice.
Ineffective Platelet Production in Thrombocytopenic Human Immunodeficiency Virus–Infected Patients
Authors: James L. Cole, Ulla M. Marzec, Clifford J. Gunthel, Simon Karpatkin, Lydia Worford, I. Birgitta Sundell, Jeffrey L. Lennox, Janet L. Nichol, Laurence A. Harker
Journal: Blood (1998)
Pulmonary involvement in Moldova lupus study
Authors: Cebanu Mariana, Mazur-Nicorici Lucia, Sadovici Victoria, Mazur Minodora, Caun Elena, Ancuta Codrina
Journal: European Respiratory Journal (2013)

The aim: To investigate the pattern and the predictive factors of pulmonary involvement in Systemic Lupus Erythematosus (SLE) in Republic of Moldova.Methods: All subjects fulfilled the SLICC 2009 classification criteria for SLE. Socioeconomic, demographic, clinical, immunological, treatment aspects of SLE were evaluated. Activity was assessed by SLEDAI, Damage Index – by SLICC. Results:The study included 90 patients, mean age 37,8±12,1 years, female rate 88,9%, disease duration - 118,7±18,3 months. The study group was divided: group 1- patients with pulmonary manifestations – 37 (41,1%), and group II - without them – 53 (58,9%) patients. The pattern of pulmonary involvement was represented by pleuritis in 23 (25,6%), pulmonary interstitial nonspecific fibrosis (PINS) in 5 (5,6%), isolated pulmonary hypertension in 3 (3,3%), pulmonary embolism 2 (2,2%) and association of more than two in 4 (4,4%) patients. Pulmonary involvement occurred after mean disease duration of 18 months with pleuritis, other involvements were observed later in the course of the disease. The pulmonary lesions were directly correlated with Raynaud syndrome, pulmonary embolism - with antiphospholipidic antibodies. The pulmonary manifestations were associated with joint involvement and were independent to renal involvement. The activity of SLE by SLEDAI more than 16 points at the time of diagnosis was predictive for pulmonary damage at 52,2±0,52 months. Cutaneous manifestations are supposed to be a protective factor for lupus lung disease. Conclusion: Pulmonary involvement in SLE patients in MOldova LUpus Study was 41,1% cases. Predictor factors for early respiratory involvement were high activity of lupus, Raynaud and antiphosfpholipid syndromes.
Familial Invasive Breast Cancers: Worse Outcome Related to BRCA1 Mutations
Authors: Dominique Stoppa-Lyonnet, Yan Ansquer, Hélène Dreyfus, Chantal Gautier, Marion Gauthier-Villars, Edwige Bourstyn, Krishna B. Clough, Henri Magdelénat, Pierre Pouillart, Anne Vincent-Salomon, Alain Fourquet, Bernard Asselain
Journal: Journal of Clinical Oncology (2000)

Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients with BRCA1 breast cancer.A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of breast and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database.Forty BRCA1 mutations were found among the 183 patients (22%). Median follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =.002), and had a higher frequency of negative estrogen (P =.003) and progesterone receptors (P =.002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers than for noncarriers (5-year rate, 80% v 91%, P =.002). Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent prognostic factor.Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than those who do not.
Evaluating Robustness and Sensitivity of the NanoString Technologies nCounter Platform to Enable Multiplexed Gene Expression Analysis of Clinical Samples
Authors: Margaret H. Veldman-Jones, Roz Brant, Claire Rooney, Catherine Geh, Hollie Emery, Chris G. Harbron, Mark Wappett, Alan Sharpe, Michael Dymond, J. Carl Barrett, Elizabeth A. Harrington, Gayle Marshall
Journal: Cancer Research (2015)

Abstract Analysis of clinical trial specimens such as formalin-fixed paraffin-embedded (FFPE) tissue for molecular mechanisms of disease progression or drug response is often challenging and limited to a few markers at a time. This has led to the increasing importance of highly multiplexed assays that enable profiling of many biomarkers within a single assay. Methods for gene expression analysis have undergone major advances in biomedical research, but obtaining a robust dataset from low-quality RNA samples, such as those isolated from FFPE tissue, remains a challenge. Here, we provide a detailed evaluation of the NanoString Technologies nCounter platform, which provides a direct digital readout of up to 800 mRNA targets simultaneously. We tested this system by examining a broad set of human clinical tissues for a range of technical variables, including sensitivity and limit of detection to varying RNA quantity and quality, reagent performance over time, variability between instruments, the impact of the number of fields of view sampled, and differences between probe sequence locations and overlapping genes across CodeSets. This study demonstrates that Nanostring offers several key advantages, including sensitivity, reproducibility, technical robustness, and utility for clinical application. Cancer Res; 75(13); 2587–93. ©2015 AACR.
Eosinophilic pustular folliculitis.
Authors: ROLF HOLST
Journal: British Journal of Dermatology (1976)

A case of eosinophilic pustular folliculitis (Ofuji) is presented. This long‐lasting disease of unknown aetiology has hitherto been reported only from Japan. It is characterized by tinea‐like slowly growing rings and by blood eosinophilia. The histological changes are epidermal infiltrations and abscesses of predominantly eosinophilic leukocytes, often localized to the follicles.
Metapneumovirus pneumonia in allogeneic stemcell transplant recipients
Authors: Adrian Egli, Jörg Halter, Dominik Heim, Martin Stern, Christoph Bucher, Hans Hirsch, Michael Tamm
Journal: European Respiratory Journal (2011)

Infectious and noninfectious pulmonary complications are frequent in allogeneic stemcell transplant recipients (SCT) and associated with a high morbidity and mortality. Metapneumovirus (MPV) has recently been recognised to cause lethal infections in immunocompromised patients. Following an index case with fatal outcome we included PCR for Metapneumovirus in the routine work-up of BAL performed in hematological patients with pulmonary symptoms. We analysed the clinical presentation and outcome of 8 allogeneic stemcell transplant recipients with a median age of 45 year observed over a period of 12 months. Median Time to pulmonary MPV infection was 473 days after SCT. 6 of 8 patients were under immunosuppressive therapy for GvHD and 4 of them had biopsy proven bronchiolitis obliterans. All patients suffered from cough and 7/8 from fever. CT scan of the chest revealed a groundglas pattern in all but one cases. There were nodules in five cases and alveolar-interstitial infiltrates in also 5 cases. Enlarged lymphnodes were only present in one patient. In one patient there was concomitant infection with moraxella catharalis. Two patients showed viral double infection in the BAL (MPV/coronavirus; MPV/rhinovirus). All patients were hospitalizid because of marked symptoms or hypoxemia. Anemia was the most frequent sideeffect of antiviral treatment. 7 out of 8 patients recovered. The patient who died had developed MPV pneumonia within one month following SCT.   Conclusion:  Metapneumovirus pneumonia is not uncommon following allogeneic stemcell transplantation. Typical clinical features include fever, cough and a groundglas pattern on chest CT scan. Most patients recover under treatment with immunoglobulins and ribavarin.
Microarray profiling of COPD patients versus non-COPD smokers reveals possible disease biomarkers
Authors: Dimitris Kampas, Eirini Neofytou, Nikolaos Soulitzis, Despina Dermitzaki, Nikolaos Siafakas, Eleni Tzortzaki
Journal: European Respiratory Journal (2013)

Background: The development and progression of COPD involves several cellular populations (lung pneumocytes, macrophages, lymphocytes) and a vast network of intracellular processes (such as apoptosis, oxidative DNA damage repair, transcription activation, etc.) that permanently alter the lung epithelium.  Objective: To analyse the whole genome of COPD patients versus non-COPD smokers in order to identify gene clusters with differential expression that could be potentially used as disease biomarkers.  Methods: Lung tissue samples from 5 selected COPD patients (GOLD stage II) and 5 non-COPD smokers were subjected to microarray analysis, using the U133 Plus 2.0 Array chip by Affymetrix.  Results: Data analysis revealed numerous genes with different expression among the two study groups. We focused our interest on the genes with the highest (>5-fold) and lowest expression (  Conclusions: These data suggest that there are essential differences in the lung epithelium expression profile between COPD patients and non-COPD smokers. There are several candidate genes that their role in COPD development and progression should be further investigated.
Re: Gunnar Steineck, Anders Bjartell, Jonas Hugosson, et al. Degree of Preservation of the Neurovascular Bundles During Radical Prostatectomy and Urinary Continence 1 Year after Surgery. Eur Urol 2015;67:559–68
Authors: Nicholas Faure Walker, Rajesh Nair, Chris Anderson
Journal: European Urology (2015)
Treatment of Metastatic Pancreatic Cancer
Authors: Andrew H. Ko, Margaret A. Tempero
Journal: Journal of the National Comprehensive Cancer Network (2005)

Pancreatic adenocarcinoma represents the fourth-leading cause of cancer-related mortality in the United States. The vast majority of patients are diagnosed at advanced stages of the disease when surgery is no longer an option. For these patients, systemic therapy remains the mainstay of care. Although single-agent gemcitabine has remained the standard of care since its approval in 1997, improvements in patient outcomes may potentially be realized by (1) applying pharmacokinetic principles to optimize drug delivery, such as the administration of gemcitabine at a "fixed-dose rate" infusion; (2) combining gemcitabine with other cytotoxic agents for which evidence of synergy exists, such as platinum compounds; and (3) integrating novel targeted agents such as bevacizumab, erlotinib, and cetuximab into treatment paradigms, based on an increasing understanding of the molecular pathways that govern pancreatic tumor growth and maintenance. This article provides the evidence to support each of these approaches and highlights future directions in the management of metastatic pancreatic cancer.
Safety, efficacy and tolerability of half-dose sofosbuvir plus simeprevir in treatment of Hepatitis C in patients with end stage renal disease
Authors: Bhamidimarri Kalyan Ram, Czul Frank, Peyton Adam, Levy Cynthia, Hernandez Maria, Jeffers Lennox, Roth David, Schiff Eugene, O’Brien Christopher, Martin Paul
Journal: Journal of Hepatology (2015)
WNT5A antagonizes canonical WNT/β-catenin signaling in lung epithelial cells
Authors: Hoeke Baarsma, Melanie Königshoff
Journal: European Respiratory Journal (2013)

Rationale:  The WNT signaling pathways are important in lung repair and tissue remodeling. Canonical WNT signaling is defined by activation β-catenin signaling, whereas non-canonical WNT signaling does not. β-Catenin signaling is reduced in alveolar epithelial cells in emphysema, a pathological feature of COPD. The mechanisms involved in WNT/β-catenin down regulation are unknown. We investigated the cross-talk between canonical and non-canonical WNT signaling in lung epithelial cells.  Methods:  Human and murine lung epithelial cells were treated with the WNT ligands WNT3A and WNT5A. β-Catenin signaling was activated by GSK3 inhibition. WNT signaling was monitored by β-catenin sensitive luciferase assay (TOP/FOP-flash) and immunoblotting.  Results:  Stimulation of lung epithelial cells with WNT3A led to LRP6 phosphorylation, β-catenin stabilization and activation of TOP/FOP-flash reporter, confirming canonical WNT signaling. WNT5A did not activate β-catenin signaling, but induced DVL phosphorylation indicating non-canonical WNT signaling. Co-stimulation with WNT3A and various doses of WNT5A resulted in a dose-dependent decrease in TOP/FOP-flash reporter activation, due to attenuated LRP6 phosphorylation and decreased β-catenin stabilization. GSK3 inhibition activated TOP-flash luciferase activity, which was antagonized WNT5A. Basal signaling by WNT5A was mediated by PKC, but not JNK or TAK1. Importantly,  WNT5A  was up regulated in the lungs of mice after cigarette smoke exposure.  Conclusion:  Canonical WNT signaling activated by either WNT3A or by GSK3 inhibition is attenuated by the non-canonical WNT ligand WNT5A in lung epithelial cells. HB is supported by an ERS long-term fellowship (LTRF 79-2012).
Arterial Chemoreceptors: Cell to System
Journal: Thorax (1995)

Book noticesrisk of severe adverse event (adjusted RR = 1 0) -that is, increased risk was entirely due to patients with more severe disease being prescribed fenoterol.The possibility that fen- oterol was intermediate in the causal pathway (and thus responsible for an increased ad- mission rate) was addressed by demonstrating that the lower strength preparation of fen- oterol (100 jg in combination with ip- ratropium) was associated with a higher risk of serious adverse event (crude RR = 2-2, 95% CI 0-6 to 10) than the higher strength pre- paration (200 pg) (crude RR= 1-5, 95% CI 0 5 to 6-1), thus demonstrating biological
Abstract 2713: Molecular Imaging of Cardiac Stem Cell Mediated Angiogenic Gene Therapy
Authors: Xiaoyan Xie, Feng Cao, Ahmad Y Sheikh, Zongjin Li, Xuetao Pei, Sanjiv S Gambhir, Ren-Ke Li, Robert C Robbins, Joseph C Wu
Journal: Circulation (2006)

Introduction: Cardiac stem cell therapy remains hampered by acute donor cell death post transplant and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells cap...
Single-Arm, Open-Label Phase II Study of Intravenously Administered Tirapazamine and Radiation Therapy for Glioblastoma Multiforme
Authors: J. Del Rowe, C. Scott, M. Werner-Wasik, J.P. Bahary, W.J. Curran, R.C. Urtasun, B. Fisher
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This phase II study tested the efficacy and safety of tirapazamine (Sanofi Synthelabo Research, Malvern, PA), a bioreductive agent, in glioblastoma multiforme (GBM) patients. The patients were staged according to a model constructed by a recursive partitioning analysis (RPA) of glioma patients in prior Radiation Therapy Oncology Group (RTOG) trials and compared with a matched standard population, as predicted by the model. PATIENTS AND METHODS: A total of 124 patients diagnosed with a GBM were treated with radiation therapy and intravenous tirapazamine between January 27,1995, and April 25,1997. All patients received 60 Gy in 2-Gy fractions. Tirapazamine was delivered three times a week for 12 treatments during radiotherapy. Fifty-five patients received tirapazamine at 159 mg/m 2 . A second dose level, 260 mg/m 2 , was opened, and 69 patients were entered. RESULTS: There was no significant survival advantage to the drug in any RPA class at either dose level. The median survival time was 10.8 months for the patient population treated with the 159-mg/m 2 dose of tirapazamine and 9.5 months for the group treated with the 260-mg/m 2 dose of tirapazamine. Survival times by RPA class for patients receiving tirapazamine at 159 mg/m 2 were 27.4 months (class III), 10.8 months (class IV), 7.9 months (class V), and 3.8 months (class VI). Survival times by RPA class for patients receiving tirapazamine at 260 mg/m 2 were 16.2 months (class III), 10.3 months (class IV), 5.1 months (class V), and 1.3 months (class VI). Patients in RPA class III treated in the 159 mg/m 2 dose arm had a notably longer survival than patients in the RTOG database RPA class III, but the difference did not reach statistical significance. There were no fatal toxicities. Grade 3/4 toxicities were more frequent at the higher dose level. CONCLUSION: Survival in the population treated with radiation and tirapazamine was equivalent to the control population. Patients in RPA class III treated with radiation and tirapazamine at the 159-mg/m 2 dose had a longer survival when compared with the historical controls. The improvement in survival did not reach statistical significance. Toxicity was acceptable in both treatment arms, but grade 3/4 toxicities were more frequent in the higher dose regimen.
Angiogenesis and lymphangiogenesis in bronchial asthma
Authors: A. Detoraki, F. Granata, S. Staibano, F. W. Rossi, G. Marone, A. Genovese
Journal: Allergy (2010)

Neovascularization plays a prominent role in inflammation and tissue remodeling in several chronic inflammatory disorders. Vessel number and size, vascular surface area and vascular leakage are all increased in biopsies from patients with asthma. High levels of VEGF and other angiogenic factors have been detected in tissues and biological samples of patients with asthma and correlate with disease activity and inversely with airway hyper-responsiveness. Inflammation in the lung stimulates the growth of new blood vessels and these contribute to the airway obstruction or airway hyper-responsiveness, or both. Effector cells of inflammation (human lung mast cells, basophils, eosinophils, macrophages, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. Inhaled corticosteroids reduce vascularity and growth factor expression and might modulate bronchial vascular remodeling in asthma. Specific antagonists to VEGF and other angiogenic factors and their receptors might help to control chronic airway inflammation and vascular remodeling and offer a novel approach for the treatment of chronic inflammatory lung disorders.
Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial
Authors: John D Grainger, Franco Locatelli, Thirachit Chotsampancharoen, Elena Donyush, Bunchoo Pongtanakul, Patcharee Komvilaisak, Darintr Sosothikul, Guillermo Drelichman, Nongnuch Sirachainan, Susanne Holzhauer, Vladimir Lebedev, Richard Lemons, Dagmar Pospisilova, Ugo Ramenghi, James B Bussel, Kalpana K Bakshi, Malini Iyengar, Geoffrey W Chan, Karen D Chagin, Dickens Theodore, Lisa M Marcello, Christine K Bailey
Journal: The Lancet (2015)
Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity
Authors: Isaak Quast, Christian W. Keller, Michael A. Maurer, John P. Giddens, Björn Tackenberg, Lai-Xi Wang, Christian Münz, Falk Nimmerjahn, Marinos C. Dalakas, Jan D. Lünemann
Journal: Journal of Clinical Investigation (2015)

IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. In contrast, the presence of sialic acid abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in decreased levels of C3b deposition on the cell surface. Similar to monoclonal antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc fragments in human polyclonal IgG. In sera derived from patients with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system in which humoral immune responses mediate tissue damage, induction of IgG Fc sialylation was associated with clinical disease remission. Thus, impairment of CDC represents an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions.
Human Intestinal Lipoproteins
Authors: Peter H. R. Green, Robert M. Glickman, Christopher D. Saudek, Conrad B. Blum, Alan R. Tall
Journal: Journal of Clinical Investigation (1979)

To explore the role of the human intestine as a source of apolipoproteins, we have studied intestinal lipoproteins and apoprotein secretion in two subjects with chyluria (mesenteric lymphatic—urinary fistulae). After oral corn oil, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) output in urine increased in parallel to urinary triglyceride. One subject, on two occasions, after 40 g of corn oil, excreted 8.4 and 8.6 g of triglyceride together with 196 and 199 mg apoA-I and on one occasion, 56 mg apoA-II. The other subject, after 40 g corn oil, excreted 0.3 g triglyceride and 17.5 mg apoA-I, and, after 100 g of corn oil, excreted 44.8 mg apoA-I and 5.8 mg apoA-II. 14.5±2.1% of apoA-I and 17.7±4.3% of apoA-II in chylous urine was in the d < 1.006 fraction (chylomicrons and very low density lipoprotein). Calculations based on the amount of apoA-I and apoA-II excreted on triglyceride-rich lipoproteins revealed that for these lipid loads, intestinal secretion could account for 50 and 33% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Similarly, subject 2 excreted 48-70% and 14% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively.