tbuckley/cabot-search huggingface dataset:
Bone Scan Index: A Quantitative Treatment Response Biomarker for Castration-Resistant Metastatic Prostate Cancer
Authors: Elizabeth R. Dennis, Xiaoyu Jia, Irina S. Mezheritskiy, Ryan D. Stephenson, Heiko Schoder, Josef J. Fox, Glenn Heller, Howard I. Scher, Steven M. Larson, Michael J. Morris
Journal: Journal of Clinical Oncology (2012)

Purpose There is currently no imaging biomarker for metastatic prostate cancer. The bone scan index (BSI) is a promising candidate, being a reproducible, quantitative expression of tumor burden seen on bone scintigraphy. Prior studies have shown the prognostic value of a baseline BSI. This study tested whether treatment-related changes in BSI are prognostic for survival and compared BSI to prostate-specific antigen (PSA) as an outcome measure. Patients and Methods We retrospectively examined serial bone scans from patients with castration-resistant metastatic prostate cancer (CRMPC) enrolled in four clinical trials. We calculated BSI at baseline and at 3 and 6 months on treatment and performed univariate and bivariate analyses of PSA, BSI, and survival. Results Eighty-eight patients were scanned, 81 of whom have died. In the univariate analysis, the log percent change in BSI from baseline to 3 and 6 months on treatment prognosticated for survival (hazard ratio [HR], 2.44; P = .0089 and HR, 2.54; P &lt; .001, respectively). A doubling in BSI resulted in a 1.9-fold increase in risk of death. Log percent change in PSA at 6 months on treatment was also associated with survival (HR, 1.298; P = .013). In the bivariate analysis, change in BSI while adjusting for PSA was prognostic at 3 and 6 months on treatment (HR, 2.368; P = .012 and HR, 2.226; P = .002, respectively), but while adjusting for BSI, PSA was not prognostic. Conclusion These data furnish early evidence that on-treatment changes in BSI are a response indicator and support further exploration of bone scintigraphy as an imaging biomarker in CRMPC.
Pulmonary hypertension, systemic lupus erythematosus, and the contraceptive pill: another report.
Authors: M H Miller
Journal: Annals of the Rheumatic Diseases (1987)

I report the case of a woman with systemic lupus erythematosus who had pulmonary hypertension unassociated with chronic interstitial lung disease or pulmonary emboli. She had started taking the contraceptive pill seven months previously.
In Vitro and In Vivo Evaluation of Whitlockite Biocompatibility: Comparative Study with Hydroxyapatite and <i>β</i>‐Tricalcium Phosphate
Authors: Hae Lin Jang, Guang Bin Zheng, Jungha Park, Hwan D. Kim, Hae‐Ri Baek, Hye Kyoung Lee, Keunho Lee, Heung Nam Han, Choon‐Ki Lee, Nathaniel S. Hwang, Jae Hyup Lee, Ki Tae Nam
Journal: Advanced Healthcare Materials (2015)

Biomimicking ceramics have been developed to induce efficient recovery of damaged hard tissues. Among them, calcium phosphate‐based bioceramics have been the most widely used because of their similar composition with human hard tissue and excellent biocompatibilities. However, the incomplete understanding of entire inorganic phases in natural bone has limited the recreation of complete bone compositions. In this work, broad biomedical evaluation of whitlockite (WH: Ca 18 Mg 2 (HPO 4 ) 2 (PO 4 ) 12 ), which is the secondary inorganic phase in bone, is conducted to better understand human hard tissue and to seek potential application as a biomaterial. Based on the recently developed gram‐scale method for synthesizing WH nanoparticles, the properties of WH as a material for cellular scaffolding and bone implants are assessed and compared to those of hydroxyapatite (HAP: Ca 10 (PO 4 ) 6 (OH) 2 ) and β‐tricalcium phosphate (β‐TCP: β‐Ca 3 (PO 4 ) 2 ). WH‐reinforced composite scaffolds facilitate bone‐specific differentiation compared to HAP‐reinforced composite scaffolds. Additionally, WH implants induce similar or better bone regeneration in calvarial defects in a rat model compared to HAP and β‐TCP implants, with intermediate resorbability. New findings of the properties of WH that distinguish it from HAP and β‐TCP are significant in understanding human hard tissue, mimicking bone tissue at the nanoscale and designing functional bioceramics.
The early days of IVF outside the UK
Authors: Jean Cohen, Alan Trounson, Karen Dawson, Howard Jones, Johan Hazekamp, Karl-Gösta Nygren, Lars Hamberger
Journal: Human Reproduction Update (2005)

In this article the history of IVF in geographical regions outside the UK are traced by pioneers of that time. Following the birth of Louise Brown in 1978, live births after IVF occurred in Australia in 1980, in the USA in 1981 and in Sweden and France in 1982. Following the first IVF birth in Australia, the Government of Victoria established a review of IVF research and practice which led to the proclamation of the Infertility (Medical Procedures) Act 1984, the first legislation to regulate IVF and its associated human embryo research. Despite such restriction, IVF doctors and scientists from Victoria, especially those under the leadership of Carl Wood, Alan Trounson and Ian Johnston continued to initiate new treatments for infertility and new methods for delivering this treatment. In the USA IVF research began on animals as early as the 1930s, when Pincus and Enzmann at Harvard were involved in attempts at IVF in the rabbit. In the 1940s, John Rock attempted human IVF with 138 human oocytes without success. In 1965, Bob Edwards was with Georgeanna and Howard Jones at Johns Hopkins where attempts were made to fertilize oocytes in vitro. Clinical IVF began in earnest in the USA in 1980 with the first birth in 1981 achieved by the use of HMG—a first successful use with IVF. In France, two groups Frydman and Testart (Clamart) and Cohen, Mandelbaum and Plachot (Sevres) focused their research in particular directions. In 1981, the Clamart group developed a plasma assay for the initial rise in LH. The Sevres group developed a transport technique. Plachot produced a long series of cytogenetic analyses of oocytes and human embryos. Mandelbaum described the microstructures of the human oocyte. The start of IVF in France benefited from the help of animal researchers from the Institut National de la Recherche Agronomique. The first babies were born in Clamart in February 1982 and in Sèvres in June 1982. Important contributions to the development of IVF from the Nordic countries include techniques for ovarian stimulation, sonographic techniques for monitoring and vaginal oocyte retrieval and also unique possibilities for monitoring IVF safety. These developments, in combination with relatively permissive laws for the practice of reproductive medicine and relatively generous reimbursement policies, as well as a general public confidence in IVF, have led to an exceptionally high availability of IVF, within international comparison.
Peer-Delivered Smoking Counseling for Childhood Cancer Survivors Increases Rate of Cessation: The Partnership for Health Study
Authors: Karen M. Emmons, Elaine Puleo, Elyse Park, Ellen R. Gritz, Rita M. Butterfield, Jane C. Weeks, Ann Mertens, Frederick P. Li
Journal: Journal of Clinical Oncology (2005)

Cancer survivors smoke at rates that are only slightly lower than the general population. This article reports on the final outcomes of Partnership for Health, a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study (CCSS).This study is a randomized control trial with follow-up at 8 and 12 months that involved smokers (n = 796) enrolled onto the CCSS cohort. Participants were randomly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor, tailored and targeted materials, and free nicotine replacement therapy. The intervention was delivered by telephone and postal service mail.The quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month (16.8% v 8.5%; P < .01) and 12-month follow-ups (15% v 9%; P < or = .01). Controlling for baseline self-efficacy and readiness to change, the intervention group was twice as likely to quit smoking, compared with the self-help group. Smoking cessation rate increased with an increase in the number of counseling calls. The cost of delivering the intervention was approximately 300 dollars per participant. The incremental cost-effectiveness of the intervention compared with controls was 5,371 dollars per additional quit.Interventions to prevent future illnesses are of critical importance to childhood cancer survivors. The Partnership for Health intervention resulted in a doubling of smoking cessation quit rates. Because of the seriousness of smoking among childhood cancer survivors, this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke.
Eosinophil granulocytes are activated during the remission phase of ulcerative colitis
Authors: M Lampinen
Journal: Gut (2005)

The aim of this study was to establish a method of investigating intestinal eosinophil and neutrophil granulocytes by flow cytometry, and to compare the distribution and activity of these cells in different stages of ulcerative colitis (UC).Biopsy samples were taken from six locations of the entire colon and from the terminal ileum in 10 patients with active total UC, 10 patients with inactive total UC, eight patients with active distal UC, and 11 control subjects. Cell suspensions from biopsies and from peripheral blood were incubated with fluorophore conjugated monoclonal antibodies. The use of scatter plot-gating and specific antibodies was established in a flow cytometry assay.Eosinophils were more numerous and more active in patients with active UC than in controls. Interestingly, during inactive UC, the number of activated eosinophils was even larger. Eosinophil activity was high in the rectum of patients with distal colitis but was also slightly elevated in the proximal colon. Neutrophils were increased in number and activity during active but not inactive UC. In patients with distal colitis, activated neutrophils were only found in the sigmoid colon and rectum.With this method, we confirm that neutrophils participate in the inflammatory process during active UC, and that they express a resting phenotype during remission. The finding of activated eosinophils in inflamed intestine strengthens the view of these cells as proinflammatory and tissue damaging. Nevertheless, our new finding of high eosinophil activation during inactive UC suggests that eosinophils play a role in repair of injured epithelium.
Quality Assessment of Genetic Markers Used for Therapy Stratification
Authors: I.M. Ambros, J. Benard, M. Boavida, N. Bown, H. Caron, V. Combaret, J. Couturier, C. Darnfors, O. Delattre, J. Freeman-Edward, C. Gambini, N. Gross, C.M. Hattinger, A. Luegmayr, J. Lunec, T. Martinsson, K. Mazzocco, S. Navarro, R. Noguera, S. O’Neill, U. Pötschger, S. Rumpler, F. Speleman, G.P. Tonini, A. Valent, N. Van Roy, G. Amann, B. De Bernardi, P. Kogner, R. Ladenstein, J. Michon, A.D.J. Pearson, P.F. Ambros
Journal: Journal of Clinical Oncology (2003)

Therapy stratification based on genetic markers is becoming increasingly important, which makes commitment to the highest possible reliability of the involved markers mandatory. In neuroblastic tumors, amplification of the MYCN gene is an unequivocal marker that indicates aggressive tumor behavior and is consequently used for therapy stratification. To guarantee reliable and standardized quality of genetic features, a quality-assessment study was initiated by the European Neuroblastoma Quality Assessment (ENQUA; connected to International Society of Pediatric Oncology) Group.One hundred thirty-seven coded specimens from 17 tumors were analyzed in 11 European national/regional reference laboratories using molecular techniques, in situ hybridization, and flow and image cytometry. Tumor samples with divergent results were re-evaluated.Three hundred fifty-two investigations were performed, which resulted in 23 divergent findings, 17 of which were judged as errors after re-evaluation. MYCN analyses determined by Southern blot and in situ hybridization led to 3.7% and 4% of errors, respectively. Tumor cell content was not indicated in 32% of the samples, and 11% of seemingly correct MYCN results were based on the investigation of normal cells (eg, Schwann cells). Thirty-eight investigations were considered nonassessable.This study demonstrated the importance of revealing the difficulties and limitations for each technique and problems in interpreting results, which are crucial for therapeutic decisions. Moreover, it led to the formulation of guidelines that are applicable to all kinds of tumors and that contain the standardization of techniques, including the exact determination of the tumor cell content. Finally, the group has developed a common terminology for molecular-genetic results.
Nasal inflammation and compliance with nasal CPAP therapy in obstructive sleep apnoea (OSA)
Authors: Mohammed AlAhmari, Raymond Sapsford, Jadwiga Wedzicha, John Hurst
Journal: European Respiratory Journal (2012)

Background:  CPAP is the standard therapy for treating OSA (1). However, CPAP can cause undesirable nasal side effects that compromise compliance (2).   Aims and objectives:  Over a six month period, we assessed the association between nasal inflammation using nasal wash interleukin (IL-6) concentration and compliance with therapy.   Methods:  Twenty-two patients were recruited with new confirmed OSA. Daily CPAP use was prospectively recorded on diary cards. Nasal wash IL-6 and diary cards for compliance were performed at no CPAP and at 1, 3 and 6 months post-CPAP. Pearson correlation was conducted to assess the relationships. A P value    Results:  The twenty-two patients (mean age±SD: 59.5±7.5 years) had AHI of mean (SD) 30.2±15.9.  We found a significant relationship between increased nasal IL-6 and decrease in compliance at baseline and six month of CPAP therapy, Pearson [r: -.517; P=0.014].   Conclusion:  Our results show that nasal inflammation relates to compliance with CPAP therapy in OSA.   References:   1. Kushida, C.A.  et al.  Sleep 2006; 29:375-380.  2. Pepin, J.L.  et al.  Chest 1995; 107:375-381.
Carbon nanomaterials as contrast agents for breast cancer diagnosis and therapy
Authors: Sara Dolci, Valentina Domenici, Gianpaolo Vidili, Elisabetta Avitabile, Marco Orecchioni, Alberto Bianco, Lucia Delogu
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Nanotechnology is the promise to fight breast cancer (BC) more specifically and effectively [[1][1]]. In this context carbon nanomaterials (CNs) have attracted the scientific community and the public interest [[2][2]]. Common modalities for BC diagnosis are ultrasonography (US)
Identifying core domains to assess flare in rheumatoid arthritis: an OMERACT international patient and provider combined Delphi consensus
Authors: Susan J Bartlett, Sarah Hewlett, Clifton O Bingham, Thasia G Woodworth, Rieke Alten, Christoph Pohl, Ernest H Choy, Tessa Sanderson, Annelies Boonen, Vivian Bykerk, Amye L Leong, Vibeke Strand, Daniel E Furst, Robin Christensen
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> For rheumatoid arthritis (RA), there is no consensus on how to define and assess flare. Variability in flare definitions impairs understanding of findings across studies and limits ability to pool results. The OMERACT RA Flare Group sought to identify domains to define RA flares from patient and healthcare professional (HCP) perspectives. <h3>Methods</h3> Flare was described as a worsening of disease activity of sufficient intensity and duration to consider a change in therapy. International patients and HCPs participated in separate and combined rounds of Delphi exercises to rate candidate flare domains previously generated in patient focus groups. Core domains were defined as those with ≥70% ratings of being 'essential' according to the third/final Delphi exercise. <h3>Results</h3> The final Delphi included 125 RA patients from 10 countries and 108 HCPs from 23 countries who rated 14 domains. Patients had a mean (±SD) age of 56±12 years and disease duration of 18±12 years. HCPs included physicians from clinical practice/research and industry, allied health providers and researchers with 17±11 years experience. Core domains comprised: pain (93%), function (89%), swollen joints (84%), tender joints (81%), participation (81%), stiffness (79%), patient global assessment (76%) and self-management (75%). Fatigue (68%), which did not reach group consensus, will receive additional consideration. <h3>Conclusions</h3> As part of the process to develop a measure for RA flare, patients and HCPs agreed on eight core domains. Next steps include identifying items to assess domains and conducting studies to validate and refine a new measure.
PTU-107 Nafld in Patients with Severe Asthma
Authors: H Gordon, P Patel, J Hull, K Nimako, A Menzies-Gow
Journal: Gut (2013)

<h3>Introduction</h3> NAFLD is a spectrum of liver disease that encompasses Nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The pathophysiology is not fully understood, but is believed to be a combination of insulin resistance leading to steatosis and subsequent oxidative injury. Known risk factors include obesity, diabetes and dyslipidaemia. Severe asthma may entail frequent corticosteroid use and a sedentary lifestyle; both predispose to risk factors implicated in NAFLD. As such we hypothesised a link between asthma and NAFLD, and a possible under detection of NAFLD amongst patients with severe asthma. <h3>Methods</h3> We audited the investigation and management of NAFLD amongst patients under the care of the Difficult Asthma Team at the Royal Brompton Hospital. We conducted a retrospective study of patients who were entered into the National Asthma Database following investigations under the Difficult Asthma Protocol (DAP) between 2007 and 2011. The following were included: Age at diagnosis, liver function (at initial assessment and most recent), liver imaging, glucose and lipids at initial investigation, and medication history. <h3>Results</h3> 209 subjects were included in the audit, all of whom entered into the National Asthma Database between 2007 and 2011. Mean age was 45 at presentation to RBH. <h3>Abnormal Liver Function</h3> 20% (n = 41) patients had abnormal liver function tests either at first presentation to RBH or on their most recent blood tests. Only 14 (34%) were further investigated with liver imaging. Of those with deranged liver function who were imaged, 79% (n = 11) had radiological evidence of NAFLD. <h3>Management of patients with confirmed NAFLD</h3> Of the patients with confirmed NAFLD only 27% (n = 3) had their fasting lipids and glucose measured. 18% (n = 2) were prescribed a statin and a similar number were prescribed metformin. <h3>Asthma medications of patients subsequently diagnosed with NAFLD</h3> 81% of patients were prescribed aminophylline. 54% were prescribed montelukast and 81% patients were prescribed oral corticosteroids. 36% of patients were treated with omalizumab (anti-IgE). <h3>Conclusion</h3> Amongst our cohort of wevere asthmatics a substantial proportion have deranged liver function. Of those with abnormal LFT who underwent imaging, a high proportion (79%) had radiological evidence of NAFLD. However 66% of patients with deranged LFT did not proceed to liver imaging. This suggests that NAFLD is currently under diagnosed and managed in this patient population <h3>Disclosure of Interest</h3> None Declared
Survival and prognostic factors in BRCA1-associated breast cancer
Authors: C.T.M. Brekelmans, C. Seynaeve, M. Menke-Pluymers, H.T. Brüggenwirth, M.M.A. Tilanus-Linthorst, C.C.M. Bartels, M. Kriege, A.N. van Geel, C.M.G. Crepin, J.C. Blom, H. Meijers-Heijboer, J.G.M. Klijn
Journal: Annals of Oncology (2005)
Nontraditional Risk Factors for Cardiovascular Disease in Diabetes
Authors: V. Fonseca, C. Desouza, S. Asnani, I. Jialal
Journal: Endocrine Reviews (2004)

People with type 2 diabetes are disproportionately affected by cardiovascular disease (CVD), compared with those without diabetes. Traditional risk factors do not fully explain this excess risk, and other "nontraditional" risk factors may be important. This review will highlight the importance of nontraditional risk factors for CVD in the setting of type 2 diabetes and discuss their role in the pathogenesis of the excess CVD morbidity and mortality in these patients. We will also discuss the impact of various therapies used in patients with diabetes on nontraditional risk factors.
<i>Borrelia burgdorferi</i> basic membrane proteins A and B participate in the genesis of Lyme arthritis
Authors: Utpal Pal, Penghua Wang, Fukai Bao, Xiuli Yang, Swapna Samanta, Robert Schoen, Gary P. Wormser, Ira Schwartz, Erol Fikrig
Journal: The Journal of Experimental Medicine (2007)

Lyme arthritis results from colonization of joints by Borrelia burgdorferi and the ensuing host response. Using gene array–based differential analysis of B. burgdorferi gene expression and quantitative reverse trancription-polymerase chain reaction, we identified two paralogous spirochete genes, bmpA and bmpB, that are preferentially up-regulated in mouse joints compared with other organs. Transfer of affinity-purified antibodies against either BmpA or BmpB into B. burgdorferi–infected mice selectively reduced spirochete numbers and inflammation in the joints. B. burgdorferi lacking bmpA/B were therefore generated to further explore the role of these proteins in the pathogenesis of Lyme disease. B. burgdorferi lacking bmpA/B were infectious in mice, but unable to persist in the joints, and they failed to induce severe arthritis. Complementation of the mutant spirochetes with a wild-type copy of the bmpA and bmpB genes partially restored the original phenotype. These data delineate a role for differentially produced B. burgdorferi antigens in spirochete colonization of mouse joints, and suggest new strategies for the treatment of Lyme arthritis.
Aberrantly activated EGFR contributes to enhanced IL-8 expression in COPD airways epithelial cells via regulation of nuclear FoxO3A
Authors: Shyamala Ganesan, Benjamin L Unger, Adam T Comstock, Kristen A Angel, Peter Mancuso, Fernando J Martinez, Umadevi S Sajjan
Journal: Thorax (2012)

Decreased activity of forkhead transcription factor class O (FoxO)3A, a negative regulator of NF-κB-mediated chemokine expression, is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Previously, we showed that quercetin reduces lung inflammation in a murine model of COPD. Here, we examined the mechanisms underlying decreased FoxO3A activation and its modulation by quercetin in COPD human airway epithelial cells and in a COPD mouse model.Primary COPD and normal human airway epithelial cells were treated with quercetin, LY294002 or erlotinib for 2 weeks. IL-8 was measured by ELISA. FoxO3A, Akt, and epidermal growth factor (EGF) receptor (EGFR) phosphorylation and nuclear FoxO3A levels were determined by Western blot analysis. Effects of quercetin on lung chemokine expression, nuclear FoxO3A levels and phosphorylation of EGFR and Akt were determined in COPD mouse model.Compared with normal, COPD cells showed significantly increased IL-8, which negatively correlated with nuclear FoxO3A levels. COPD bronchial biopsies also showed reduced nuclear FoxO3A. Decreased FoxO3A in COPD cells was associated with increased phosphorylation of EGFR, Akt and FoxO3A and treatment with quercetin, LY294002 or erlotinib increased nuclear FoxO3A and decreased IL-8 and phosphorylation of Akt, EGFR and FoxO3A, Compared with control, elastase/LPS-exposed mice showed decreased nuclear FoxO3A, increased chemokines and phosphorylation of EGFR and Akt. Treatment with quercetin partially reversed these changes.In COPD airways, aberrant EGFR activity increases PI 3-kinase/Akt-mediated phosphorylation of FoxO3A, thereby decreasing nuclear FoxO3A and increasing chemokine expression. Quercetin restores nuclear FoxO3A and reduces chemokine expression partly by modulating EGFR/PI 3-kinase/Akt activity.