tbuckley/cabot-search huggingface dataset:
Abstract 4945: Targeting ErbB3-addicted cancers across the HER2 spectrum
Authors: Matthew Onsum, Defne Yarar, Violette Paragas, Bo Zhang, Stephanie Nguyen, Birgit Schoeberl, Charlotte McDonagh, Gavin MacBeath, Ulrik Nielsen
Journal: Cancer Research (2012)

Abstract ErbB3 is a critical activator of phosphoinositide 3-kinase (PI3K) signaling in EGFR-, HER2-, and MET-addicted cancers, and ligand-driven activation of ErbB3 is a prominent method by which cancers become resistant to targeted inhibitors of ErbB signaling, as well as anti-hormonal and chemotherapeutic agents. With the goals of inhibiting survival signaling in cancer cells, delaying the onset of resistance to standard-of-care therapies, and re-sensitizing cancer cells to prior therapies, we developed an anti-ErbB3 monoclonal antibody, MM-121, that effectively blocks ligand-dependent activation of ErbB3 and induces internalization and degradation of the receptor. The activity of single-agent MM-121 was examined in xenograft models and a machine-learning algorithm was developed that accurately predicts which preclinical models of cancer will respond to MM-121 based on five protein-based biomarkers. By simulating ErbB3 inhibition using a computational model of ErbB signaling, we predicted that a bispecific molecule that docks onto HER2 and subsequently binds to ErbB3 would effectively block ErbB3-driven signaling in HER2-amplified tumors. We therefore developed a bispecific antibody comprising two human scFv antibodies linked by a modified form of human serum albumin. The resulting molecule, MM-111, forms a trimeric complex with HER2 and ErbB3, effectively inhibiting ErbB3 signaling and demonstrating antitumor activity in preclinical models that are dependent on HER2 overexpression. Both MM-121 and MM-111 are now in early stages of clinical development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4945. doi:1538-7445.AM2012-4945
Viral Hepatitis, Type B (MS-2 Strain)
Authors: Jerrold J. Lander, Joan P. Giles, Robert H. Purcell, Saul Krugman
Journal: New England Journal of Medicine (1971)

Abstract Further observations of the natural history and prevention of viral hepatitis Type B revealed that all 25 unimmunized susceptible children who had a parenteral exposure to MS-2 serum had evidence of hepatitis B infection; 25 had hepatitis B antigen, and 24 had an abnormal SGOT. Of 15 children who received standard immune serum globulin after a parenteral exposure to MS-2 serum, 13 had detectable hepatitis B antigen, and 12 had an abnormal SGOT. Of 10 children who received hepatitis B immune serum globulin after a parenteral exposure to MS-2 serum, four had detectable hepatitis B antigen and abnormal SGOT; of 29 children who received one to three inoculations of heat-inactivated MS-2 serum before a parenteral exposure to unheated MS-2 serum, 12 had detectable hepatitis B antigen and abnormal SGOT. The use of these active and passive immunizing procedures was associated with a protective effect, a more attenuated hepatitis B infection, and a decreased chronic carrier rate of hepatitis B antigen.
OP0315 Ultrasound Features of Inflammation in the Knee Joint and its Relationship to Pain and Radiographic Osteoarthritis
Authors: M. C. Hall, P. Courtney, S. Doherty, K. Latief, W. Zhang, M. Doherty
Journal: Annals of the Rheumatic Diseases (2013)

Background  Ultrasound (US) is a useful imaging modality that allows the evaluation of features suggestive of inflammation in osteoarthritis (OA). US features are more common in those with painful knee OA but the association between them remains inconclusive.  Objectives  To determine: [1] whether the frequency of ultrasound (US) features of inflammation differs between people with (a) normal asymptomatic knees (controls); (b) knee pain (KP) with no radiographic osteoarthritis (ROA); (c) asymptomatic ROA; and (d) symptomatic ROA (SROA); [2] whether US features associate with knee pain, OA change on x-ray, or symptoms and signs of inflammation; and [3] whether US features change in parallel with temporal change in knee pain.  Methods  A multiple group case-control study design was used. Community participants were recruited and divided into 4 groups based on presence or absence of (1) knee pain and (2) ROA. Standardised knee radiographs and assessments for pain, stiffness and function were carried out. All underwent US examination for effusion, synovial hypertrophy, popliteal cysts and power Doppler signal (PD) within the synovium. Features were dichotomised as present/absent, and grey-scale features were measured directly in mm. Follow-up US and pain assessments were collected in some OA and non-OA participants after 3 months.  Comparisons between groups were examined using Χ 2  tests, one-way ANOVA and post-hoc Bonferroni tests. Logistic regression was used to examine association between US features, knee pain and ROA adjusting for age, sex and BMI.  Results  243 participants were recruited: 90 controls, 59 with KP, 32 with ROA and 62 with SROA. Greyscale US features of inflammation were more common in SROA (effusion 92%, synovial hypertrophy 82% and popliteal cysts 39%) than control and KP participants (p  Conclusions  US features of inflammation are most strongly associated with ROA but the relationship with symptoms is less clear. This supports synovial changes as predominantly a secondary rather than primary feature of OA. Further studies are warranted to confirm these findings.  Acknowledgements  We are grateful to Arthritis Research UK for funding this work (AHP Training Fellowship Grant no.18861).  Disclosure of Interest  None Declared
Benefit of Carotid Endarterectomy in Patients with Symptomatic Moderate or Severe Stenosis
Authors: Henry J.M. Barnett, D. Wayne Taylor, Michael Eliasziw, Allan J. Fox, Gary G. Ferguson, R. Brian Haynes, Richard N. Rankin, G. Patrick Clagett, Vladimir C. Hachinski, David L. Sackett, Kevin E. Thorpe, Heather E. Meldrum, J. David Spence
Journal: New England Journal of Medicine (1998)

Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up.
S4 Occupational asthma; is this the cause of excess respiratory symptoms and COPD described in bitumen exposed workers?
Authors: N. Surange, J. Hoyle
Journal: Thorax (2011)

<h3>Introduction</h3> Epidemiological studies suggest increased risk of asthma and COPD in asphalt exposed workers.1 Bitumen is used in this industry. In this case we describe occupational asthma caused by bitumen exposure in a lab environment. This is the first such report to our knowledge. <h3>Case History</h3> A 49-year old male with no history of asthma or atopy and &lt;5 pack years smoking history presented with airflow obstruction on surveillance spirometry, cough and wheeze. He analysed hot bitumen samples (1900 C) in a lab environment without using respiratory protective equipment. Spirometry FEV<sub>1</sub> 57%, FVC 85% ratio 55%. Respiratory symptoms improved after 3 weeks off work, returning soon after he rejoined the lab. Peak flow rates were variable and lower at work. Analysis with OASYS scored 3.08 (Abstract S4 figure 1). Histamine challenge test was positive (PC<sub>20</sub> 2.216 mg/ml). Skin prick test to paraldehyde was positive. After 8 weeks away from the exposed environment the subject was asymptomatic, continued to have obstructive spirometry but improved bronchial reactivity (PC<sub>20</sub> 7.489 mg/ml) without medication and improved peak flows with little diurnal variation. One week after restarting work the respiratory symptoms returned. Repeat OASYS charts scored 3.14 with histamine reactivity similar to baseline (PC<sub>20</sub> 2.81 mg/ml) after 4 weeks. A specific challenge test was not possible due to the problems with heating bitumen to 1900<sup>°</sup>C in the hospital lab. <h3>Conclusion</h3> The progression of symptoms and lung function in relation to work history supports the diagnosis of occupational asthma induced by bitumen fume exposure. This has not been reported previously. The possible mechanisms include sensitisation to short chain aldehydes, produced by partial combustion of bitumen which oxidises at these temperatures. Other potential sensitisers contained in bitumen are nickel and vanadium. Further studies are needed to investigate the by-products of heated bitumen and whether the previously described excess of COPD and respiratory disease in these workers is due to unidentified occupational asthma from bitumen fume exposure.
P2-09-03: Breast Cancer Detection Using a Novel Functional Imaging Device Equipped with Multiparametric Computer Analysis.
Authors: T Sella, M Sklair-Levy, C Maya, M Rozin, A Tanir, S Maira, E Libson, D Izhaky
Journal: Cancer Research (2011)

Abstract Introduction: A novel prototype system performing functional three-dimensional (3D) infrared imaging (RUTH), coupled with multi-parametric computer analysis (MIRA), was evaluated for non-invasive breast cancer detection. The technique utilizes non-ionizing radiation and automatically provides risk assessment based on parameters derived from a clinically known training set. Materials and methods: Following IRB approval, prospective multi-center, two-armed blinded evaluation, was performed on 102 women, which included 43 patients with biopsy proven breast cancer and 59 women with a normal (BI-RADS 1) mammogram. RUTH imaging (Real Imaging Ltd, Israel) was acquired on a continuous temporal timeline for 5 minutes during which a cold-stress test was applied for one minute. Acquired data were analyzed using multiple computed algorithms (MIRA) which were combined to develop a master algorithm for risk assessment of breast cancer. Analysis was blinded to the clinical status. Results were displayed as risk assessment scale with 100 being suspicious for breast cancer and −100 inferring normal healthy breasts. Results Thirty-nine of 43 cancers (91.7%) were identified using this novel technology. The sensitivity and specificity of RUTH coupled with MIRA for detecting breast cancer were 90.7% and 67.8% respectively. The AUC defined by the ROC curve was 0.832. Twenty-seven of the 39 (70%) detected cancers were smaller than 20mm in size. Conclusions: This preliminary study shows adequate performance of the novel technology examined for detecting breast cancer. Performance is comparable to the reported performance of new adjunctive breast imaging technologies such as tomosynthesis and contrast-enhanced mammography, and superior to the published sensitivity of mammography. Our results warrant further evaluation of the RUTH and MIRA technologies in detecting and characterizing breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-03.
Abstract 1439: De novo expression of c-kit in prostate cancer cells interacting with the bone microenvironment
Authors: Xiaoning Zhe, Sanaa M. Nabha, Anju Mukundan, Craig N. Giroux, Michael L. Cher, R. Daniel Bonfil
Journal: Cancer Research (2010)

Abstract Specific cellular and molecular interactions between prostate cancer (PC) cells and the bone microenvironment lead to expansion of the metastatic deposit, disease progression, and ultimately significant morbidity and mortality. We recently reported an association between expression of the tyrosine kinase receptor c-kit and clinical PC progression, with the highest expression seen in clinical metastatic bone specimens. Moreover, we found that intraosseous tumors formed by otherwise c-kit negative PC3 cells injected into human bone xenografts in SCID mice (SCID-hu model) expressed c-kit. To determine the relevance of these findings, we examined additional human PC cell lines, namely LNCaP, C42b, and DU145, for the expression of c-kit in vitro and in vivo. While none of the cultured PC cells expressed c-kit at the message or protein level, immunostaining for c-kit in intraosseous tumors produced by these cells in the SCID-hu model revealed a distinctive and specific reactivity in the cancer cell compartment. The induction of c-kit expression in PC cells growing within the bone microenvironment was emulated by co-culture of PC3 cells and bone-derived cells embedded in Matrigel, as demonstrated by RT-PCR analysis. In an attempt to mimic the de novo c-kit expression observed in the SCID-hu model and to identify potential signaling pathways triggered by c-kit activation by its ligand stem cell factor (SCF), normally expressed by the bone microenvironment, we transiently transfected PC3 cells with wild-type c-kit. Activation of c-kit was confirmed by immunoblotting for phosphorylated c-kit. Using the whole human genome Agilent microarray, we found that 220 genes were differentially expressed when SCF-treated and non-treated c-kit-transfected PC3 cells were compared, resulting in discrete functional sub-networks that were coordinately up or down-regulated. Most notably, pathway and genetic network analysis revealed that c-kit activation resulted in an up-regulated fibroblast growth factor-2-mediated sub-network. Taken together, these results suggest that c-kit induction in PC cells in the bone microenvironment modulates cell-cell interaction pathways and growth factor signaling systems that ultimately lead to expansion of bone metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1439.
Micro Management: Understanding How Diesel Exhaust Particles Alter Cellular Processes
Authors: Cynthia Washam
Journal: Environmental Health Perspectives (2009)

Greenhouse gas emissions are widely acknowledged to be contributing to climate change-related health effects that vary by location, and are expected to continue doing so for many years, even if substantial emission cuts occur.A workgroup of the Council of State and Territorial Epidemiologists has identified a set of indicators that it says will allow national and local officials in the United States to better predict any such changes and consequences and to take appropriate action as it becomes warranted [EHP 117:1673-1681; English et al.].The team also identified the data needed for tracking these indicators and ascertained whether the data exist, must be improved, or must be generated.They say this is the first effort to synthesize and evaluate related information published by many sources.The team determined the best indicators of environmental changes due to climate change are quantity of greenhouse gas emissions, air quality (in particular ozone), air mass stagnation events (such as those caused by temperature inversions), temperature and humidity, pollen loads, ragweed occurrence, drought incidence, drinking water scarcity, and occurrence of wildfires and harmful algal blooms.Data for some of these indicators are strong and/or expected to improve soon, as in the case of greenhouse gases, temperature, air mass stagnation events, and drought.Data on other indicators, such as pollen, harmful algal blooms, and ozone, require substantial improvement.For indicators of human death and illness, the authors recommend tracking
SP0038 Chronic nonbacterial osteomyelitis
Authors: H. Girschick
Journal: Annals of the Rheumatic Diseases (2013)

Chronic nonbacterial osteomyelitis CNO is an inflammatory disorder of the musculoskeletal system with yet unknown etiology. In addition to bone inflammation, patients may present with inflammation of other tissues including e.g. the joints, the skin or the gut. Differential diagnosis is done by exclusion. Recently, the search for a causative etiology has identified mutations in the alkaline phosphatase gene or the interleukin-1 receptor antagonist (IL1RN) gene in a few patients presenting with a clinical picture resembling CNO. In addition, monocytes from CNO patients in general exhibited a reduced IL-10 expression in response to LPS stimulation that is independent of <i>IL10</i> promoter polymorphisms. Thus, impaired MAPK signaling in CNO monocytes in response to LPS stimulation has been described as a potential causative mechanism. Of note, for the majority of patients no monogenetic or metabolic cause can be identified. So far the published cohorts of patients were mainly based on local pediatric rheumatology centers or national cohorts. Thus, the Eurofever consortium tried to build up an international database gathering and describing the clinical and laboratory findings of 329 CNO patients. The history, clinical symptoms, laboratory and imaging data were reviewed blindly by the CNO EUROFEVER faculty. In 327 patients the diagnosis was confirmed, in 2 the diagnosis seemed likely. To our knowledge, this is by far the largest CNO group reported in the literature. Cohort description: 263 patients below the age of 18 and 66 patients above 18 were registered. 113 were male and 216 female. 311 patients were caucasian, 10 of other origin. 14 countries participated in the study. The age at disease onset was 11.8 years (STDEV 7.9 a), the age at diagnosis was 12.9 years (mean; STDEV 8,1 a). The CNO EUROFEVER data will be introduced to the EULAR PReS audience. In addition, therapeutic strategies based on a long-term follow up cohort will be presented. *The Eurofever consortium: Hermann Girschick, Tobias Schwarz, Christine Beck, Annette Jansson, Susanne Schalm, Henner Morbach, Aldo Naselli, Isabelle Koné-Paut, Antonella Insalaco, Susan Nielsen, Troels Herlin, Sulaiman M. Al-Mayouf, Michael Hofer, Pierre Quartier, Christina Boros, Jasmin Kuemmerle-Deschner, Rosa Merino, Loredana Lepore, Silvana Martino, Tamas Constantin, Marija Jelusic-Drazic, Irina Nikishina, Marco Gattorno, Nicolino Ruperto. <h3>Disclosure of Interest</h3> None Declared
Four Ectopic Parathyroid Glands Detected With Tc-99m Sestamibi
Authors: CHARLES W. SUTTER, DAVID K. SHELTON
Journal: Clinical Nuclear Medicine (1997)

A 30-year-old woman with a history of end-stage renal disease secondary to hypertension on ambulatory peritoneal dialysis for the past 2 years had back pain. Lumbar plain films showed evidence of renal osteodystrophy. Lab results showed an elevated serum-calcium and parathyroid-hormone levels. A diagnosis of hyperparathyroidism was made, and a Tc-99m sestamibi scan was performed to localize an abnormal parathyroid gland. The scan showed four ectopic parathyroid glands. Pathology showed nodular hyperplasia in all four glands.
SAT0155 Scores on the MDHAQ for “Walk 2 Miles or 3 Kilometers,” “Poor Sleep” and “Participate in Recreation,” Which Are not on the Haq, Indicate Poorer Status than Scores from the Haq: Data from the United States and Australia:
Authors: I. Castrejόn, M.J. Bergman, K.A. Gibson, J. Meyerhoff, G. Luta, E.P. Davoudzadeh, T. Pincus
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are significantly better in recent years than in previous decades.<sup>1</sup> Health assessment questionnaire (HAQ) scores were almost always elevated in 1980 when the HAQ<sup>2</sup> was reported; in 1999, 16% of patients had HAQ scores of zero, suggesting "no difficulty" in function, but most nonetheless reported problems with function as well as psychosocial issues, reflecting "floor effects."<sup>3</sup> Therefore, a multidimensional HAQ (MDHAQ) was developed to include 13 queries in the user-friendly HAQ format, 8 simple activities of daily living (ADL) from (and identical to) the HAQ, and 5 not on the HAQ: 2 complex activities – "walk 2 miles or 3 kilometers" and "participate in recreation and sports as you would like"; and 3 "psychological" queries – sleep quality, anxiety and depression. <h3>Objectives</h3> To analyze mean scores for each of 13 MDHAQ items in 3 rheumatology settings, 2 in the USA and one in Australia, to recognize their capacity to document improved clinical status. <h3>Methods</h3> All patients at 3 settings in Ridley Park, PA USA, Baltimore, MD USA and Liverpool, NSW, Australia complete an MDHAQ at each visit in the reception area before seeing the physician. The MDHAQ queries 13 items (Table) in the patient-friendly HAQ format, all scored 0-3, with 4 response options: without any difficulty=0, with some difficulty=1, with much difficulty=2 and unable to do=3. Mean scores were analyzed in 224 RA patients in PA USA, 432 visits of 72 RA patients in MD USA, and 228 patients with all rheumatic diseases (RD) in Australia. Statistical significance was evaluated using Wilcoxon signed rank tests. <h3>Results</h3> Mean scores &gt;0.88 (0-3 scale) were seen at all 3 sites for 3 of the 13 items in all patient groups, "walk 2 miles/3 kilometers," "participate in recreation/sports as you would like" and "poor sleep", 3 of the 5 MDHAQ items not found on the HAQ. Scores varied at the 3 sites, but patterns were similar. <h3>Conclusions</h3> The MDHAQ identifies patient problems that are not captured by the HAQ, similarly in USA and Australia, which may be valuable in clinical management and documentation of improvement over time, not possible when baseline scores are zero. The MDHAQ might be included in usual clinical care and in clinical trials. <h3>References</h3> Arthritis Rheum 2005;52:1009. Arthritis Rheum 1980;23:137. Arthritis Rheum 1999;42:2220. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3458
P174 Utility Of Needle Aspiration In Patients With Primary Spontaneous Pneumothorax With Complete Lung Collapse: A Retrospective 5-year Study
Authors: M. Ganaie, S. Bikmalla, M. Afridi, M. Khalil, I. Hussain, M. Haris
Journal: Thorax (2014)

<h3>Introduction</h3> Primary spontaneous pneumothorax (PSP) is a common presentation. Despite being known for over 200 years, there is variation in definition criteria and treatment recommendations. Previous studies comparing needle aspiration (NA) with intercostal drain (ICD) for all primary spontaneous pneumothoraces requiring intervention including those with complete lung collapse have shown no difference in immediate success, early failure and recurrence rate. There is no separate treatment algorithm for PSP with complete lung collapse in the current British Thoracic Society pneumothorax guidelines. We aimed to compare NA with ICD as the first intervention in this sub-group. <h3>Methods</h3> We conducted a retrospective observational study of 735 consecutive pneumothorax episodes between March 2008 and December 2013. Those with secondary spontaneous pneumothorax, history of trauma and iatrogenic pneumothorax were excluded. Pneumothorax with no visible aerated ipsilateral lung on plain chest radiograph was defined as ‘PSP with complete lung collapse’. Patient case records and plain chest radiographs were reviewed. Values of p &lt; 0.05 were considered statistically significant. <h3>Results</h3> Of the 735 episodes, 233 (32%) were PSP. 61 PSP patients were identified to have complete lung collapse on chest radiograph. 32 patients had NA and 29 ICD as the first intervention. There was no statistically significant difference between the two groups in terms of age, sex, smoking history and symptoms. Compared to the NA group, patients with ICD had significantly better immediate success rate (66% vs. 10%; p &lt; 0.0001) and lower rate of recurrence (3% vs. 31%; p = 0.0064). Median length of stay was similar in both groups. Almost a third of the patients in both groups required a definitive surgical intervention. <h3>Conclusion</h3> Our results suggest significantly better success with ICD as the first intervention in the management of PSP with complete lung collapse and there was no added benefit of NA. We propose a further sub group of PSP with complete lung collapse in which NA should not be attempted.