tbuckley/cabot-search huggingface dataset:
Testing of the filter function of a prototype device to eliminate fetal surrogate markers and bacterial load for autotransfusion in postpartum haemorrhage in low-resource settings
Authors: Brandon Collofello, Nuriya Robinson, Valerie Dobiesz, Pam Kutz, Abby Koch, Amanda Harrington, Hananeh Esmailbeigi, Stacie Geller
Journal: The Lancet Global Health (2016)

Background Postpartum haemorrhage is a leading cause of death in low-income and middle-income countries, but it is also largely preventable. As a potential solution for restoring blood volume in women with life-threatening haemorrhage in low-resource settings, a vaginal blood collection drape with adaptations for autotransfusion has been created. In this study, we aimed to assess the filtration function of the autotransfusion system prototype and to determine the degree to which the filter removes surrogate markers for amniotic fluid, fetal cells, and inhibin A, as well as to quantify the reduction of bacterial contaminants in postpartum blood after vaginal delivery.
Alemtuzumab in Kidney-Transplant Recipients
Authors: James F. Markmann, Jay A. Fishman
Journal: New England Journal of Medicine (2011)

Over the past decade, the use of induction therapy in organ-transplant recipients to intensify immunosuppression during the peritransplantation period has contributed to a reduction in early rejection rates and graft loss in the first year after transplantation. It is now common practice to select from among available induction therapies on the basis of risk–benefit considerations for the individual patient. As of 2008, induction agents were administered in 82% of kidney recipients. These agents were administered less often in lung (57%), heart (47%), and liver (26%) recipients; such recipients usually received less potent agents that do not deplete T cells.1 Induction . . .
Chemosensitivity Testing of Circulating Epithelial Cells (CETC) in Breast Cancer Patients and Correlation to Clinical Outcome.
Authors: K. Pachmann, E. Stein, G. Spitz, E. Schill, U. Pachmann
Journal: Cancer Research (2009)

Abstract In spite of ample prognostic markers available in breast cancer, still a considerable proportion of patients with good prognostic markers suffers relapse whereas patients with poor prognostic markers may remain disease free. It would, therefore, be desirable to control, at the individual patient level, whether the applied therapy is effective. Our previous work indicates, that in cancer patients most of the epithelial cells circulating in peripheral blood (CETC) are part of the tumor and that the response of these cells reflects the response of the tumor to the applied therapies.Therefore, these cells were used to assay chemosensitivity in short time cultures analyzing the percent of cell killing during short time incubation and monitoring the decrease or increase in numbers of these cells during treatment with the respective agents providing a unique tool for therapy surveillance. Patients were prospectively analysed for the number of CETC before each new combination of chemotherapy. 1ml of blood was drawn into EDTA vials, red blood cells lysed and the white blood cell pellet stained with FITC-labelled anti-Epcam. Green fluorescent cells were detected by image analysis and dead cells excluded due to red PI fluorescence. Activity of individual compounds was determined using three different concentrations of each compound at 3h, 6h and 12hs and displayed as % cell killing. The in vitro results were then compared to in vivo reduction of CETCs and to the reduction of a marker lesion.215 patients have been investigated so far. Cell killing was dose and time dependent. The highest killing rates were observed with Epirubicin and Taxanes, agents which are known for their high activity in breast cancer. Less than 20% killing activity was termed marginal activity. In vitro sensitivitity was highly significantly predictive of in vivo CETC reduction. In some cases an increasing resistance could be shown to develop during repeated cycles of the same combination therapy. CETC reduction was correlated with a prolonged progression free survival.Thus this approach can in the future be used to test in advance the sensitivity of the circulating tumor cells to chemotherapy and at the same time monitor the current response of the cells to therapy in vivo in order to optimize and individualize therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2044.
The spread of hepatitis C virus genotype 1a in North America: a retrospective phylogenetic study
Authors: Jeffrey B Joy, Rosemary M McCloskey, Thuy Nguyen, Richard H Liang, Yury Khudyakov, Andrea Olmstead, Mel Krajden, John W Ward, P Richard Harrigan, Julio S G Montaner, Art F Y Poon
Journal: The Lancet Infectious Diseases (2016)
Health secretary announces drive to clear 12 month waiting list backlog
Authors: C. White
Journal: BMJ (2014)

The health secretary, Jeremy Hunt, has told NHS hospitals in England to clear their “unacceptable” backlog of patients who have been waiting more than 12 months for treatment, even if this means breaching the 18 week referral to treatment target for other patients.

In a speech to staff at the Royal Surrey County Hospital in Guildford on 4 August, the health secretary said that it was “unacceptable” for patients who were in pain or discomfort to wait a long time for their treatment.1 “No one should have to wait more than a year for treatment” without good reason, he said, adding that he wanted the numbers to be “as close to zero as possible.”

As of May …
Abstract 510: Identification and characterization of immunogenic epitopes from CD133 and their potential for use to immunologically target cancer stem cells
Authors: Clemencia Pinilla, Valeria Judkowski, Alcinette Bunying, Jianfei Ji, Zhenhua Li, James Bender, John S. Yu
Journal: Cancer Research (2012)

Abstract CD133 is a marker that identifies cancer stem cells (CSC) on many solid tumors and its expression has been correlated with shortened survival. Although expressed on many normal tissues and stem cells, CD133 is overexpressed on CSC and normal SC are negative or express low levels of MHC making them less sensitive to recognition by CD8+ cytotoxic T lymphocytes (CTL). Potential CTL epitopes were identified by algorithms to predict binding to HLA-A2. Binding studies showed high affinity binding and low off rates for four candidate epitopes. CTL induction studies using IL-12 secreting dendritic cells to stimulate CD8+ T cells evaluated the immunogenicity of the candidate peptides after three or four weekly in vitro stimulations. Multimer and IFNγ responses were observed with CD133-753, 405 and 708 epitopes. Subsequent studies demonstrated killing of T2 cells loaded with peptide. To evaluate the potential for autoimmunity, mouse homolog peptides of the 753 and 405 epitopes that were shown to have high affinity binding to human HLA-A2 were used to immunize HLA-A2 transgenic mice (9CB6F1-Tg (HLA-A*0201/H2-Kb) A*0201). Mice were immunized 3 times at 3 week intervals in IFA + HBV helper peptide and spleens were harvested 2 weeks after the last immunization and stimulated in vitro for one week with peptide pulsed LPS stimulated- APC. An additional group was sacrificed 6 weeks after the last immunization and studied. IFNγ ELISpot assays showed immune responses to the 753 and 405 peptides in 35% and 40% of mice. Organs, including heart, lung, liver, kidney, stomach, intestine, brain, bone marrow, gonads, and eyes from mice with immune responses were found to be negative for lymphocytic infiltrations supporting a lack of autoimmunity related to the immune response to these peptides. Together these studies support the safety and immunogenicity of these peptides as a potential vaccine to target CD133 cancer stem cells. 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 510. doi:1538-7445.AM2012-510
Interferon Alfa plus Chemotherapy for Non-Hodgkin's Lymphoma: Five-Year Follow-up
Authors: Janet W. Andersen, Richard V. Smalley
Journal: New England Journal of Medicine (1993)

To the Editor: As we previously reported (November 5, 1992, issue),1 interferon alfa, when added to a four-drug, doxorubicin-based chemotherapy regimen, is an effective antitumor agent in patients with clinically aggressive low-grade or intermediate-grade non-Hodgkin's lymphoma. This study has now reached a median follow-up period for survival of 5.25 years. At five years, 81 percent of the patients assigned to a regimen of cyclophosphamide, vincristine, prednisone, and doxorubicin (COPA) and 66 percent of those assigned to this regimen plus interferon alfa (I-COPA) had disease progression. The time to treatment failure continues to be significantly prolonged (P = 0.0013) by the . . .
Brain and White Matter Hyperintensity Volumes After 10 Years of Random Assignment to Lifestyle Intervention
Authors: Mark A. Espeland, Kirk Erickson, Rebecca H. Neiberg, John M. Jakicic, Thomas A. Wadden, Rena R. Wing, Lisa Desiderio, Guray Erus, Meng-Kang Hsieh, Christos Davatzikos, Barbara J. Maschak-Carey, Paul J. Laurienti, Kathryn Demos-McDermott, R. Nick Bryan
Journal: Diabetes Care (2016)

OBJECTIVE Type 2 diabetes increases the accumulation of brain white matter hyperintensities and loss of brain tissue. Behavioral interventions to promote weight loss through dietary changes and increased physical activity may delay these adverse consequences. We assessed whether participation in a successful 10-year lifestyle intervention was associated with better profiles of brain structure. RESEARCH DESIGN AND METHODS At enrollment in the Action for Health in Diabetes clinical trial, participants had type 2 diabetes, were overweight or obese, and were aged 45–76 years. They were randomly assigned to receive 10 years of lifestyle intervention, which included group and individual counseling, or to a control group receiving diabetes support and education through group sessions on diet, physical activity, and social support. Following this intervention, 319 participants from three sites underwent standardized structural brain magnetic resonance imaging and tests of cognitive function 10–12 years after randomization. RESULTS Total brain and hippocampus volumes were similar between intervention groups. The mean (SE) white matter hyperintensity volume was 28% lower among lifestyle intervention participants compared with those receiving diabetes support and education: 1.59 (1.11) vs. 2.21 (1.11) cc (P = 0.02). The mean ventricle volume was 9% lower: 28.93 (1.03) vs. 31.72 (1.03) cc (P = 0.04). Assignment to lifestyle intervention was not associated with consistent differences in cognitive function compared with diabetes support and education. CONCLUSIONS Long-term weight loss intervention may reduce the adverse impact of diabetes on brain structure. Determining whether this eventually delays cognitive decline and impairment requires further research.
THU0170 Is Rheumatoid Arthritis Cervical Spine Involvement Decreasing Over Time? Results from a Systematic Review: Table 1
Authors: T. Zhang, J.E. Pope
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> RA complications seem less common including vasculitis, nodules, corneal melts and rheumatoid neck involvement with damage. <h3>Objectives</h3> The prevalence and progression of anterior atlanto-axial subluxations (aAAS), vertical subluxations (VS), subaxial subluxations (SA) and associated cervical myelopathy in rheumatoid arthritis (RA) over the past 50 years were determined. <h3>Methods</h3> A literature search was performed using Medline-OVID/EMBASE, PubMed, and Scopus (from 1960 to June 21, 2014). Prevalence studies were included if the sample size was at least 100 or the prevalence/progression of cervical subluxations was reported. Study quality was assessed using the STROBE checklist. Prevalence of cervical subluxations was calculated for each study. Student9s t test and meta-regression was used to evaluate for significance. <h3>Results</h3> A total of 12,249 citations were identified with 59 studies included. The prevalence of aAAS decreased from 36% (95%CI: 30%&gt;42%) before 1980s to 24% (95%CI: 13%&gt;36%) in 2000s (p=0.04). The overall prevalence of VS was 11% (95%CI: 10%&gt;19%), 13% (95%CI: 12%&gt;20%) for SA and cervical myelopathy 5% (95%CI: 3%&gt;9%) without significant temporal changes. Rate of progression of aAAS, VS, and SAS subluxations was 4, 6, and 3 lesions per 100 patients per year, respectively. The incidence of new or progressive cervical myelopathy occurred at 2 cases per 100 patients with known cervical subluxations per year. Characteristics of studies (every other study is shown) with progression of C spine lesions in RA: <h3>Conclusions</h3> Since the 1960s, only aAAS has decreased dramatically. It is still more than twice as common as VS or SAS. No temporal changes in development of cervical myelopathy in affected RA patients were noted. The progression rate of cervical subluxations and myelopathy was unchanged over time. <h3>Disclosure of Interest</h3> None declared
Abstract 3747: The impact of lipid inflammatory mediators on colon cancer initiating cells.
Authors: Anita Sjölander, Kishan Bellamkonda, Wondossen Sime
Journal: Cancer Research (2013)

Abstract Past studies links the lipid inflammatory mediators at the tumor microenvironment to the colorectal cancer, however their impact on the colon cancer initiating cells (CICs) is largely unknown. Accordingly, the present study aimed to identify the possible link between lipid inflammatory mediators and CICs. In lack of robust marker for identifying colon CICs, we initially screen five different colon cancer cell lines (HCT-116, Caco-2, SW-480 SW-620 and HT-29) for their percentage occurrence using well-established stem cell markers i.e. CD133, CD44 and ALDH. The Flow cytometeric sorting of CD133, CD44 and ALDH subpopulations showed large variation in their population size in these cell lines. Further we noted that ALDH is relatively better marker of these to identify CICs. This statement was based on our observation of markedly increased capacity of ALDH+ cells to produce colonies rather than ALDH− cells. We sorted ALDH+/CICs and investigated the effect of lipid inflammatory mediators such as leukotriene D4 (LTD4) or prostaglandin E2 (PGE2) on these cells. It was noted that LTD4 and PGE2 stimulations not only enriched the relative population of ALDH+ cells; it also greatly improved the colony forming capacity of these cells. Moreover, we observed that ALDH+ cells were more resistant to 5-Fluorouracil (5-FU) treatment compared to ALDH− cells. Furthermore the qPCR data revealed that Bcl-2, COX-2, Bcl-3, ALDH1B1, GLI1 and KLF4 genes were largely amplified in ALDH+ cells in presence of LTD4 or PGE2, indicating their probable impact on the stemness pool of these cells. In conclusion our study shows that lipid inflammatory mediators can affect the survival and stemness of CICs. Citation Format: Anita Sjölander, Kishan Bellamkonda, Wondossen Sime. The impact of lipid inflammatory mediators on colon cancer initiating cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3747. doi:10.1158/1538-7445.AM2013-3747
Abstract 5221: Angiogenesis Imaging of Orthotopic Bladder Tumors using a Smart MRI Contrast Agent Containing VEGF121/rGel
Authors: Jaemoon Yang, Eun-Jin Cho, Khalid A. Mohamedali, Carol J. Farhangfar, Walter N. Hittelman, Jin-Suck Suh, Michael G. Rosenblum, Yong-Min Huh
Journal: Cancer Research (2010)

Abstract Comprehension of the angiogenic vessels from solid tumors and metastatic lesions is a crucial step for the treatment of cancer. In particular, recognition of VEGFR-2 (KDR) as primary proangiogenic factors and their distribution analysis is very important for establishment of the treatment strategy. In this research, we thus formulated the smart imaging probes based on VEGF121/rGel conjugated MnFe2O4 for imaging of tumor neovasculature using an orthotopic bladder tumor xenograft model. VEGF121/rGel was conjugated to MnFe2O4 nanoparticles (MNPs). Their colloidal size was around 45 nm and a high relaxivity coefficient was 423 mM−1s−1. As in vitro test, the targeting efficiency and detection capability of the VEGF121/rGel-MNPs were investigated in both KDR deficient (253JB-V) and KDR-overexpressing (PAE/KDR) cell lines using MRI, respectively. The targeting and internalization of VEGF121/rGel-MNPs into cells was confirmed by electron microscopy. Their phosphorylation ability and cytotoxicity were compared to unconjugated VEGF121/rGel. They demonstrated astonishing targeting capability against KDR-overexpressing PAE/KDR cells, as confirmed by dose-dependent MR images and VEGF121 inhibition tests. The phosphorylation activity of KDR and cytotoxicity of VEGF121/rGel-MNPs were evaluated. The orthotopic tumor mouse model was established by implanting low KDR-expressing 253JB-V cells into the bladder dome. After tail-vein injection of VEGF121/rGel-MNPs, the MR signal enhancement of intratumoral vessels by VEGF121/rGel-MNPs was observed and inhibition test using VEGF121 was also conducted. VEGF121/rGel-MNPs successfully targeted the tumor and provided accurate anatomical details through: i) acquisition of clear neoangiogenic vascular distributions and ii) obvious enhancement of the MR signal in T2*-weighted images. Immunostaining and blocking studies demonstrated the specific targeting ability of VEGF121/rGel-MNPs towards intratumoral angiogenesis. Furthermore, ex vivo MR imaging of tumor tissue, and a CD-31 and rGel fluorescence immunostaining study revealed the targeting ability to VEGFR-2 on the angiogenetic vessels. Consequently, synthesized VEGF121/rGel-MNPs as valuable MR imaging contrast agents can be specifically delivered to tumors and bind to KDR-expressing angiogenic tumor vessels. 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 5221.
Abstract A64: Calprotectin suppresses PIWIL1 and tumor growth in oral squamous cell carcinoma
Authors: Ali Khammanivong, Brent Sorenson, Brian Guenther, Karen F. Ross, Mark C. Herzberg
Journal: Cancer Research (2009)

Abstract Calprotectin (a heterodimer of S100A8 and S100A9), normally expressed in oral epithelial cells, is down-regulated in oral squamous cell carcinoma (OSCC). Carcinoma cells over-expressing calprotectin show reduced tumor growth in vivo and in vitro and are morphologically more differentiated than carcinoma cells negative for calprotectin expression. Phosphorylation of histone H3 at serine 10 (Ser10) is a marker for increased cell division, CD24 is expressed on differentiated cells and PIWIL1 plays a role in cellular self-renewal. Objective: To determine the molecular pathways involved in calprotectin-associated suppression of tumor growth and self-renewal. Methods: To study the regulatory function of calprotectin in tumor growth, a non-calprotectin expressing human epithelial carcinoma cell line (KB) was transfected with either an empty vector (KB-EGFP) or vector containing S100A8 and S100A9 genes (KB-S100A8/A9). To study the loss of function, S100A8 and S100A9 expression was silenced in calprotectin-positive OSCC cell line (TR146) by small interfering RNA. Genome wide analysis of gene regulation was compared between calprotectin-negative and calprotectin-positive KB cells using Affymetrix HG-U133A microarrays and validated by quantitative real-time RT-PCR. Changes in protein expression were examined by immunofluorescence flow cytometry. Results: Calprotectin expression in carcinoma cells increases phosphosphorylation of histone H3 (Ser10) correlating with a larger population at the cell cycle checkpoint G2/M and significant reduction in growths in vitro (KB-S100A8/A9 and TR146) and in vivo (KB-S100A8/A9). Among the cellular differentiation-associated molecules, expression of CD24 is significantly up-regulated, whereas, the expression of self-renewal factor PIWIL1 is reduced at both mRNA and protein levels when calprotectin is over-expressed. Conclusion: Calprotectin may play essential roles in suppressing tumor growth by decreasing self-renewal capability and maintaining cellular differentiation. Loss of calprotectin expression in OSCC may lead to unregulated growth and de-differentiation. This study was supported by the NIH/NIDCR grant R01DE11831. Citation Information: Cancer Res 2009;69(23 Suppl):A64.
PWE-118 An Audit of Hepatitis C Testing and Referral Patterns
Authors: L L Wong, N Todd, C Millson
Journal: Gut (2013)

<h3>Introduction</h3> The Hepatitis C action plan of 2004 identified a need to “reduce the level of undiagnosed infection and provide better, more co-ordinated pathways of care for people with hepatitis C, from their initial diagnosis to specialist care and treatment”(1). Our aim was to audit the outcome of Hepatitis C testing in a large secondary care facility in UK against the established management pathway (2). <h3>Methods</h3> Using the hospital microbiology database, we identified 3166 requests for hepatitis C serology from January to December 2011. All positive results were retrospectively analysed at least 12 months after test requests, to include: referral source, demographics, route of acquisition etc. In addition, evidence of HCV PCR testing, outpatient referral and outcomes were sought from referrers and laboratory records. <h3>Results</h3> Age range of Hepatitis C positives was from 10 months to 71 years. 41% referrals came from primary care and drug dependence services, 30% from medical service, 5% from obstetrics and 5% from GUM. 76% had acquired HCV from intravenous drug use. Alcohol dependence was recorded in 34%. Of 122 positive HCV antibodies requested, 49 (40%) were already known about. Of the remaining 73, 48 (66%) had no further investigation requested. Of these 48, 34 were not referred or investigated further (15 from primary care, 13 from secondary care, 6 from prisons). 13 were referred without PCR result, 11 did not attend (DNA’d) at first (6) or second (5) appointments, 2 have appointments outstanding and 1 had previously failed treatment but was not re-referred. <h3>Conclusion</h3> The Hepatitis C action plan has failed to deliver. This audit demonstrates almost half the serology tests are unnecessary repeats, 2/3rd of true new positives never progress down the management pathway and only 3% access treatment. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4084521 http://www.nhs.uk/hepatitisc/hcp/testing-for-hepatitis-c/Pages/from-diagnosis-to-treatment–a-flowchart.aspx
A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency
Authors: Barbara K. Burton, Manisha Balwani, François Feillet, Ivo Barić, T. Andrew Burrow, Carmen Camarena Grande, Mahmut Coker, Alejandra Consuelo-Sánchez, Patrick Deegan, Maja Di Rocco, Gregory M. Enns, Richard Erbe, Fatih Ezgu, Can Ficicioglu, Katryn N. Furuya, John Kane, Christina Laukaitis, Eugen Mengel, Edward G. Neilan, Scott Nightingale, Heidi Peters, Maurizio Scarpa, K. Otfried Schwab, Vratislav Smolka, Vassili Valayannopoulos, Marnie Wood, Zachary Goodman, Yijun Yang, Stephen Eckert, Sandra Rojas-Caro, Anthony G. Quinn
Journal: New England Journal of Medicine (2015)

Lysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia.