tbuckley/cabot-search huggingface dataset:
Detection of multiple biomarkers simultaneously using multi-colored nanoparticles in breast cancer tissues
Authors: M. Yezhelyev, C. Morris, X. Gao, M. Lewis, C. Cohen, S. Nie, R. M. O’Regan
Journal: Journal of Clinical Oncology (2005)

9525 Background: Available methods of molecular profiling of tumors are unable to detect biomarkers simultaneously on single specimens, and do not take into account tumor heterogeneity. Additionally many of these methods require tissue destruction restricting investigation of tumor microenvironment and single cell profiling. We investigated a nanotechnology-based approach to profile cancer cell biomarkers simultaneously utilizing multicolor nanoparticles, called quantum dots (QDs). QDs are photon-emitting nanoparticles, which can be engineered to emit across a wide spectrum, by altering the size of the particle. We have developed a novel method of multiplex QD-based labeling (MQDL) for in-situ analysis of biomarkers in breast cancer cell lines and xenograft tumors. Methods: Antibodies against human ER, PR, HER2 and Ki-67 were conjugated with multicolor QDs (605nm, 655nm, 565nm and 705nm respectively) and incubated with MCF-7, BT474 and MDA-MB-231 human breast cancer cell lines. Labeled antigens were visualized by laser-scanning microscopy and level of their expression was established by spectral microscopy. For in-situ tumor diagnostics frozen tumor tissues from xenografts of breast cancer origin were stained with QDs-antibody conjugates and analyzed by spectroscopy. Results: We were able to identify and quantify ER, PR, HER2 and Ki67 using conjugated QDs simultaneously on single slides of breast cancer cell lines and breast xenograft tumors. Spectroscopy revealed a curve with 4 separate peaks representing the level of expression of the analyzed antigens with each peak corresponding to the coloured identity specifically assigned to each antigen of interest in the breast cancer cells. Quantifying analysis of ER, PR, HER2 and Ki-67 expression by MQDL showed excellent correlation with routine methods. Conclusion: Simultaneous multiplex QD labeling is a new method of molecular profiling that allows determination and measurement of expression of analyzed biomarkers in single specimens of cell lines and tumor samples. MQDL can facilitate in identifying individual biomolecular protein signatures of tumors, a step necessary to design selective targeting therapy. No significant financial relationships to disclose.
Increase of syphilis in Finland related to the Russian epidemic
Authors: E Hilthunen-Back, O Haikala, P Koskela, T Reunala
Journal: Eurosurveillance (1996)

In the early 1990s only 30 to 40 new serologically confirmed cases of syphilis were reported annually in Finland. Typical syphilis patients were heterosexual men who acquired the infection abroad. Since 1993, the incidence of syphilis has increased. In 19
Programmed cell death-1 blockade in recurrent disseminated Ewing sarcoma
Authors: Georgia J. B. McCaughan, Michael J. Fulham, Annabelle Mahar, Judy Soper, Angela M. Hong, Paul D. Stalley, Martin H. N. Tattersall, Vivek A. Bhadri
Journal: Journal of Hematology & Oncology (2016)

Ewing sarcoma (EWS) is a malignant tumour of bone and soft tissue, and although many patients are cured with conventional multimodal therapy, those with recurrent or metastatic disease have a poor prognosis. Genomic instability and programmed cell death ligand-1 (PD-L1) expression have been identified in EWS, providing a rationale for treatment with agents that block the programmed cell death-1 (PD-1) receptor. In this report, we describe a heavily pre-treated patient with recurrent metastatic EWS who achieved a clinical and radiological remission with PD-1 blockade. To our knowledge, this is the first reported case demonstrating efficacy of PD-1 blockade in EWS. This warrants further investigation in particular given the poor prognosis in patients with recurrent or metastatic disease.
SP0134 Heritable Collagen Disorders
Authors: F. Malfait
Journal: Annals of the Rheumatic Diseases (2015)

Heritable collagen disorders, such as osteogenesis imperfecta (OI) and the Ehlers-Danlos syndromes, encompass a clinically and genetically heterogeneous group of Mendelian syndromes that manifest with overlapping clinical findings, especially involving the musculoskeletal, but also the cardiovascular, ophthalmologic, auditory and cutaneous systems. For many patients affected by these disorders, the musculoskeletal problems predominate the clinical picture, and often lead to a reduced quality of life. In general, there is a lack of evidence-based approaches for the treatment of these problems. Current management of patients with OI, a condition mainly characterized by a variable degree of bone fragility with recurrent bone fractures, relies on a multidisciplinary approach with rehabilitation, orthopedic surgery, and consideration of bisphosphonates treatment. The Ehlers-Danlos syndromes comprise a very heterogeneous group of heritable connective tissue disorders, primarily characterized by joint hyperlaxity, skin hyperextensibility and soft connective tissue fragility. Joint hyperlaxity, which may be localized or generalized, predisposes to joint instability and recurrent dislocations. Other complaints include reduced muscle strength and proprioception, kinesiophobia and limitations in performing daily activities. Management of these problems should focus on physical therapy and assistive devices, such as braces and ringsplints, and in general, orthopedic surgery should be delayed in favor of these treatment modalities. Chronic widespread pain is a common and challenging problem for these patients, and can be both physically and psychosocially disabling. It often requires a multidisciplinary approach, including physical therapy, pain medication and cognitive behavioral therapy, tailored to the individual's need. Disclosure of Interest None declared
AB0716 Predictive Value of DLCO Reduction in Scleroderma Patients Without Cardio-Pulmonary Involvement at Baseline
Authors: M. Colaci, D. Giuggioli, M. Sebastiani, A. Manfredi, F. Lumetti, F. Luppi, S. Cerri, C. Ferri
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Impaired diffusing capacity of the lung for carbon monoxide (DLCO) was frequently observed in systemic sclerosis (SSc) patients, generally related to the presence of interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). However, in clinical practice abnormally low DLCO values may be found also in the absence of these SSc complications. <h3>Objectives</h3> To investigate the prospective clinical relevance of isolated DLCO reduction at baseline in SSc patients. <h3>Methods</h3> Ninety-seven SSc female patients (age at the diagnosis: 51.3±14.5 years; disease duration: 10.4±6.6 years; limited/diffuse skin subsets: 92/5), without any clinical, radiological (high resolution computed tomography), and echocardiographic manifestations of ILD or PAH at baseline, nor other lung or heart diseases able to affect DLCO, were recruited at our Rheumatology Centre. Patients with DLCO &lt;55%<sup>1</sup> (15 patients; group A) were compared with those with normal DLCO (82 patients; group B), at baseline and at the end of follow-up. <h3>Results</h3> At baseline, patients of group A showed significantly higher percentage of anticentromere autoantibodies compared to group B (13/15, 86.6% vs. 48/82, 58.5%; p=0.044). More interestingly, at the end of long-lasting clinical follow-up (11.6±6.7 years), pre-capillary PAH (right heart catheterization) solely developed in some patients of group A (3/15, 20% vs. 0/82; p=0.003). <h3>Conclusions</h3> In SSc patients, the presence at baseline of isolated, marked DLCO reduction (&lt;55% of predicted) and serum anticentromere autoantibodies might characterize a peculiar SSc subset that may precede the development of PAH. Therefore, careful clinical follow-up of patients with isolated moderate-severe DLCO reduction should be mandatory. <h3>References</h3> Steen VD, Graham G, Conte C, Owens G, Medsger TA Jr. Isolated diffusing capacity reduction in systemic sclerosis. Arthritis Rheum 1992; 35:765-70. <h3>Disclosure of Interest</h3> None declared
Comparison of Finasteride (Proscar®) and Serenoa repens (Permixon®) in the Inhibition of 5-Alpha Reductase in Healthy Male Volunteers
Authors: G Strauch, P Perles, G Vergult, M Gabriel, B Gibelin, S Cummings, W Malbecq, M P Malice
Journal: European Urology (1994)
Clinical development of new drug–radiotherapy combinations
Authors: Ricky A. Sharma, Ruth Plummer, Julie K. Stock, Tessa A. Greenhalgh, Ozlem Ataman, Stephen Kelly, Robert Clay, Richard A. Adams, Richard D. Baird, Lucinda Billingham, Sarah R. Brown, Sean Buckland, Helen Bulbeck, Anthony J. Chalmers, Glen Clack, Aaron N. Cranston, Lars Damstrup, Roberta Ferraldeschi, Martin D. Forster, Julian Golec, Russell M. Hagan, Emma Hall, Axel-R. Hanauske, Kevin J. Harrington, Tom Haswell, Maria A. Hawkins, Tim Illidge, Hazel Jones, Andrew S. Kennedy, Fiona McDonald, Thorsten Melcher, James P. B. O'Connor, John R. Pollard, Mark P. Saunders, David Sebag-Montefiore, Melanie Smitt, John Staffurth, Ian J. Stratford, Stephen R. Wedge
Journal: Nature Reviews Clinical Oncology (2016)

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.
Response to antipsychotic medication: the doctor's and the consumer's view
Authors: T Van Putten, P R May, S R Marder
Journal: American Journal of Psychiatry (1984)

The subjective response to antipsychotic medication was systematically evaluated in two samples of schizophrenic patients, one treated with haloperidol, the other with thiothixene. For both groups, a dysphoric response to the first dose was found to be a powerful predictor of noncompliance. A persisting dysphoric response was associated with a poor clinical outcome. Dysphoric responses were powerfully associated with akathisia. Patients' subjective responses were consistent throughout therapy, and there was moderate agreement between the patients' evaluation of the medication and the staff's ratings of improvement. The authors suggest that the subjective response to antipsychotic medication should not be dismissed and that dysphoric responses should be acknowledged.
PTH-049 Single port laparoscopic colectomies for ibd in an elective and emergency setting; the new gold standard?
Authors: P Ainley, F Shaban, D Borowski, D Garg, T Gill
Journal: Gut (2015)

<h3>Introduction</h3> Single-port laparoscopic surgery is becoming more prevalent worldwide. Our colorectal unit is leading in UK practice in performing single-port surgery (SILS). We present our case series on elective and emergency laparoscopic total colectomies and proctocolectomies for IBD. Our aim is to compare outcomes of SILS vs. multi-port surgery. <h3>Method</h3> A retrospective study of all laparoscopic total colectomies and proctocolectomies performed in our unit for IBD between May 2009 and Dec 2014 by two Colorectal Surgeons was conducted. We collected data on emergency vs. elective, single vs. multi-port, operation time, LOS, resumption of diet, time to stoma output and complications. <h3>Results</h3> 35 cases in total were performed: 19 SILS, 14 multi-port, 1 SILS assisted, 1 multi-port assisted. There were 16 emergency cases and 19 elective. Average operative time was shorter in SILS (253 vs. 301 min). Average LOS was shorter in the SILS group (6.95 vs. 10 days). Average days to resumption of diet was shorter in the SILS group (2.00 vs. 2.80 days). Average time to stoma output was similar (2.38 days in SILS and 2.36 in Multi-port). 30-day complication rate was lower in the SILS group (15.8% vs 42.9%); there were 2 returns to theatre in the SILS group vs. 1 in the multi-port. <h3>Conclusion</h3> In our experience single port laparoscopic colectomies are a superior alternative to the traditional multi-port approach. Our figures show that it has a shorter operating time, shorter length of stay, quicker resumption of diet and a lower complication rate and we recommend that it should become the new gold standard. <h3>Disclosure of interest</h3> None Declared.
OC-056 Evaluation of a novel nurse-led one-stop clinic for patients referred for investigation of suspected non-alcoholic fatty liver disease
Authors: K Gamble, K Fancey, JK Dowman, RJ Aspinall, AJ Fowell
Journal: Gut (2015)

<h3>Introduction</h3> Non-alcoholic fatty liver disease (NAFLD) affects approximately 1 in 4 adults in the UK.<sup>1</sup>In our hospital catchment area there are an estimated 150000 individuals with NAFLD, approximately 12000 of who are likely to have advanced liver fibrosis. Our aim was to evaluate the utility of a weekly nurse-led NAFLD clinic including transient elastography (Fibroscan; TE) to screen for advanced fibrosis in the management of rising numbers of referrals to our secondary care Hepatology clinics. <h3>Method</h3> A designated referral pathway was devised in conjunction with local primary care commissioners where patients with suspected NAFLD and with a NAFLD-fibrosis score<sup>2</sup>in the indeterminate or high risk range (&gt;–1.455) were assessed in a one-stop clinic by a clinical nurse specialist using a specific clerking template. TE was performed on all patients with NAFLD and discharge to primary care with lifestyle advice considered in those with TE values below the threshold for advanced liver fibrosis/cirrhosis (7.9 kPa).<sup>3</sup>Prospective demographic and clinical data were collected on all patients seen in the clinic from May 1<sup>st</sup>–Dec 31<sup>st</sup>2014. <h3>Results</h3> A total of 112 patients were seen during the evaluation period; Male:Female 3:2, median age 59 years (range 20–91). Thirteen (12%) consumed alcohol at levels above those consistent with a diagnosis of NAFLD (females &gt;14 units/week; males &gt;21 units/week), 2 (1.8%) had autoimmune hepatitis and 2 (1.8%) had chronic hepatitis C. The remaining 95 (85%) were diagnosed with NAFLD. Amongst this NAFLD population, TE values &lt;7.9 kPa were present in 56 patients (59%), 43 of whom were discharged to primary care. This represented 45% of the NAFLD patients and 38% of all referrals made. Thirteen NAFLD patients had TE readings &lt;7.9 kPa but were followed up in consultant clinics for other clinical reasons. Thirty-three patients (35%) had TE readings ≥7.9 kPa, all of whom were followed-up in consultant clinics, as well as 6 patients (6%) in whom TE was unreliable. <h3>Conclusion</h3> A one-stop nurse-led clinic for patients with suspected NAFLD and an indeterminate or high NAFLD fibrosis score allowed early discharge of approximately 40% of the patients referred. Such clinics may be a useful way of stratifying patient risk and utilising resources effectively in the face of increasing demand on secondary care Hepatology services. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Armstrong MJ, <i>et al</i>. J Hepatol. 2012;56:234–40 Angulo P, <i>et al</i>. Hepatology 2007;45:846–54 Wong VW, <i>et al</i>. Hepatology 2010;51:454–62
Proliferation and Survival of Mammary Carcinoma Cells Are Influenced by Culture Conditions Used for Ex Vivo Expansion of CD34+Blood Progenitor Cells
Authors: A. Spyridonidis, W. Bernhardt, D. Behringer, G. Köhler, M. Azemar, A. Pflug, R. Henschler
Journal: Blood (1999)
Transdermal Uptake of Diethyl Phthalate and Di( <i>n</i> -butyl) Phthalate Directly from Air: Experimental Verification
Authors: Charles J. Weschler, Gabriel Bekö, Holger M. Koch, Tunga Salthammer, Tobias Schripp, Jørn Toftum, Geo Clausen
Journal: Environmental Health Perspectives (2015)

BackgroundFundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been experimentally evaluated and has been largely overlooked when assessing uptake of phthalate esters.ObjectivesThis study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans.MethodsIn a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air concentrations of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concentrations substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 hr later. Metabolites of DEP and DnBP were measured in these samples and extrapolated to parent phthalate intakes, corrected for background and hood air exposures.ResultsFor DEP, the median dermal uptake directly from air was 4.0 μg/(μg/m3 in air) compared with an inhalation intake of 3.8 μg/(μg/m3 in air). For DnBP, the median dermal uptake from air was 3.1 μg/(μg/m3 in air) compared with an inhalation intake of 3.9 μg/(μg/m3 in air).ConclusionsThis study shows that dermal uptake directly from air can be a meaningful exposure pathway for DEP and DnBP. For other semivolatile organic compounds (SVOCs) whose molecular weight and lipid/air partition coefficient are in the appropriate range, direct absorption from air is also anticipated to be significant.CitationWeschler CJ, Bekö G, Koch HM, Salthammer T, Schripp T, Toftum J, Clausen G. 2015. Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: experimental verification. Environ Health Perspect 123:928–934; http://dx.doi.org/10.1289/ehp.1409151
AB0278 Early Termination of the First Biological Disease-Modifying Antirheumatic Drugs Therapy Leads to Radiological Progression in Patients with Rheumatoid Arthritis, Irrespective of Subsequent Therapies
Authors: K. Minegishi, M. Hama, R. Yoshimi, Y. Kirino, M. Takeno, A. Ueda, Y. Ishigatsubo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Along with the treat-to-target concept, “hit hard and early” therapeutic strategy has been successful in rheumatoid arthritis (RA), resulting in suppression of radiological progression, particularly in patients receiving biological disease-modifying antirheumatic drugs (bDMARD). However, bDMARD is not always continued due to efficacy and safety issues in daily clinical practice. <h3>Objectives</h3> This study investigated impacts of early termination of bDMARS on radiographic progression. <h3>Methods</h3> We retrospectively reviewed clinical profiles including X-ay findings of RA patients who initiated a bDMARD as the first biologic agent since 2009 in Yokohama City University hospital. The patients were divided into two groups based on whether the first bDMARD was continued (Group A) or discontinued (Group B) one year later, irrespective of subsequent therapies. At entry, both hands were examined by X-ray and ultrasonography (US). Estimated yearly radiographic progression of the hands was calculated by van der Heijde-modified Sharp score (TSS). Bilateral wrists and all of the metacarpophalangeal and proximal interphalangeal joints were examined by power Doppler and gray scale US semiquantitatively (0-3). <h3>Results</h3> Seventy-five patients (84.0% female, mean age 59.7±14.1 years, mean disease duration 7.4±7.9 years) received a first bDMARD (infliximab n=24, etanercept n=10, adalimumab n=9, golimumab n=3, tocilizumab n=22, abatacept n=7). A total of 19 patients (25.3%), including 15 patients who started to receive a second bDMARD within the next year, discontinued initial bDMARD. The reasons of discontinuation were insufficient efficacy (n=9), adverse events (n=9) and other (n=1). At the entry, there was no significant difference in the baseline characteristics including age, gender, disease duration, DAS28, and US scores between Group A and Group B. Group B showed significantly higher DAS28 at one year (p=0.003). Based on TSS of hand X-ray, less radiographic progression was observed in 10 patients (17.9%) of Group A and 8 patients (42.1%) of Group B (p=0.032), respectively. Bone repair was detected in 3 patients of Group A. Estimated yearly radiographic progression was much greater in Group B (1.3±2.1) than Group A (0.4±1.3) (p=0.021). <h3>Conclusions</h3> Our data showed that early termination of the first bDMARD within a year was associated with future radiological progression in RA, irrespective of the reasons and subsequent therapies. Thus, appropriate selection of bDMARD in the early phase is critical to suppress bone damage and improve long-term prognosis in RA. <h3>Disclosure of Interest</h3> None declared
Relapsing vivax malaria cluster in Eritrean refugees, Israel, June 2010
Authors: E Kopel, E Schwartz, Z Amitai, I Volovik
Journal: Eurosurveillance (2010)

We report on a cluster of relapsing vivax malaria among Eritrean refugees residing in Israel. Since the beginning of 2010, 15 cases have been identified. Five of the six patients who had complete medical and epidemiological histories, reported Sudan as the place of primary infection during their journey to Israel, and having had the first relapse in Israel, six months later (median). Suggested place of exposure is the region of the Eritrean refugee camps in Sudan.