tbuckley/cabot-search huggingface dataset:
AB0103 On-demand drug delivery from self-assembled hydrogels: a new approach for treatment of inflammatory arthritis
Authors: P. Vemula, O. Levy, M. Valic, O. M. Sanchez, P. Anand, A. O. Aliprantis, J. M. Karp
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Holy Grail of drug delivery is an autonomous system that titrates the amount of drug released in response to a biological stimulus, ensuring the drug is released only when needed at a therapeutically relevant concentration.1 One of the hallmarks of inflammatory arthritis is its variable disease activity consisting of flares of inflammation punctuated by periods of reduced disease activity.2 We have developed an injectable <i>I</i>nflammation <i>R</i>esponsive self-assembled hydrogel (IR-gel) that can encapsulate and release drugs in response to enzymes that are upregulated in a diseased state including matrix metalloproteinases (MMP-2 &amp; MMP-9) and esterases. <h3>Objectives</h3> We aim to demonstrate on-demand delivery of the anti-inflammatory agent, triamcinolone acetonide (TA), in response to i) proteolytic enzymes, ii) enzymes secreted from lipopolysaccharide (LPS) activated macrophages and iii) synovial fluid (SF) collected from rheumatoid patient’s knee joint. <h3>Methods</h3> TA loaded IR-gel (100 µL) was suspended in PBS (900 µL), and enzyme (100 ng/mL) was added in a dialysis bag and immersed in 40 ml of PBS, followed by incubation at 37°C. At each time-point, an aliquot (2 ml) was collected, lyophilized, dissolved in DMSO and quantified the concentration of the drug using HPLC. Similarly, instead of enzymes, either conditioned media from activated macrophages or inflamed SF were used. <h3>Results</h3> IR-gel released TA in response to the enzymes that are expressed within arthritic joints (MMP-2, MMP-9 and esterases) as well as conditioned media of activated macrophages, a mimic of inflammation (Fig. 1). Incubation in phosphate buffer saline (PBS) at 37oC releases moderate amount of drug (&lt;20%) during a 120-day incubation. To evaluate on-demand delivery, enzymes were added to the PBS samples on day-120, which triggered the release of TA (Fig. 1B). In addition, IR-gel released TA in response to SF collected from inflamed joints, but not when incubated with normal SF (Fig. 1D). These results suggest that IR-gel responds to proteolytic enzymes to release drug on-demand. <h3>Image/graph</h3> <h3>Conclusions</h3> IR-gel can encapsulate drugs, and disassemble in response to proteolytic enzymes, yet is hydrolytically stable in healthy SF. These hydrogels may be useful to deliver drugs in an inflammation dependent manner. <h3>References</h3> Vemula PK, Cruikshank GA, Karp JM, John G. Biomaterials 2009;30:383. Wolfe F, Caplan L, Michaud K. Arthritis Rheum 2006;54:628. <h3>Disclosure of Interest</h3> None Declared
Long-term follow-up of childhood acute lymphoblastic leukemia in Tokyo Children's Cancer Study Group 1981–1995
Authors: M Tsuchida, K Ikuta, R Hanada, T Saito, K Isoyama, K Sugita, Y Toyoda, A Manabe, K Koike, A Kinoshita, M Maeda, K Ishimoto, T Sato, Y Okimoto, T Kaneko, M Kajiwara, M Sotomatsu, Y Hayashi, H Yabe, R Hosoya, Y Hoshi, M Ohira, F Bessho, Y Tsunematsu, I Tsukimoto, S Nakazawa
Journal: Leukemia (2000)
Abstract 3547: The BIM deletion polymorphism not associated with treatment efficacy of sorafenib for advanced hepatocellular carcinoma.
Authors: Yu-Yun Shao, Yung-Lin Chang, Chung-Yi Huang, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Cancer Research (2013)

Abstract Background: A germline BIM deletion polymorphism was recently proposed to predict poor treatment efficacy of certain kinase inhibitors, including imatinib and gefitinib. Sorafenib, a multi-kinase inhibitor, is the current standard treatment for advanced hepatocellular carcinoma (HCC). We aimed to explore whether BIM deletion predicted the treatment efficacy of sorafenib for advanced HCC. Methods: All patients who were enrolled in clinical trials to receive sorafenib-containing regimens as first-line therapy for advanced HCC and consented to provide peripheral blood samples were included in the study. Genomic DNA was extracted from the mononuclear cells of peripheral blood. We performed PCR and agarose gel electrophoresis to detect the genotypes with and without the BIM deletion polymorphism, and then analyzed the associations between BIM genotypes and treatment outcomes. Results: A total of 90 patients were enrolled. Among them, 64 patients received sorafenib plus metronomic tegafur/uracil, and 26 patients received sorafenib alone; 69 (77%) patients had chronic hepatitis B infection, and 18 (20%) had chronic hepatitis C infection. Most (90%) patients had BCLC stage C disease. The heterozygous BIM deletion polymorphism was identified in 9 (10%) patients. Patients with and without the BIM deletion polymorphism had similar objective response rates (12.5 % vs. 6.2%, p = 0.479) and disease control rates (55.6% vs. 60.5%, p = 0.774). Time to progression, progression-free survival, and overall survival were also similar between patients with and without BIM deletion (Table), regardless the treatment regimens. Besides, the BIM polymorphism had no associations with gender, age, hepatitis etiology, and disease stage. Conclusions: The BIM deletion polymorphism was not associated with the treatment efficacy of sorafenib for advanced HCC. (This work was supported by grants NSC98-3112-B-002-038, NSC101-2314-B-002-141, 100CAP1020-2 &amp; NTUH.101-N1965.) BIM deletion &amp; treatment outcomes BIM deletion polymorphism Yes (n = 10) No (n = 80) p value Time to progression 4.2 (0–10.5) 4.1 (3.6–4.7) 0.978 Progression-free survival 4.2 (0–10.5) 3.7 (2.7–4.8) 0.871 Overall survival 8.1 (0–187.1) 7.4 (5.6–9.1) 0.742 Data presented as median (95% confidence interval), in months Citation Format: Yu-Yun Shao, Yung-Lin Chang, Chung-Yi Huang, Chih-Hung Hsu, Ann-Lii Cheng. The BIM deletion polymorphism not associated with treatment efficacy of sorafenib for advanced hepatocellular carcinoma. [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 3547. doi:10.1158/1538-7445.AM2013-3547
Correct Integration Mediated by Integrase–LexA Fusion Proteins Incorporated into HIV-1
Authors: Michelle L. Holmes-Son, Samson A. Chow
Journal: Molecular Therapy (2002)

Fusion of wild-type or truncated integrase to a sequence-specific DNA-binding protein, such as the Escherichia coli LexA repressor, results in an integration bias toward the recognition site of the DNA-binding protein in vitro. Integrase-defective HIV-1 could become integration-competent by supplying the fusion protein in trans. To understand the mechanism of complementation, the virus–host DNA junctions of cells infected with the integrase–LexA containing virus were sequenced. The characteristic hallmarks of wild-type integration were present, a 5′-TG/CA-3′ at the ends of the viral sequence and a 5-bp direct repeat in the immediately flanking cellular DNA. Experiments were also carried out to determine the mechanism by which the amino- or carboxy-terminal truncated integrase fused to LexA restored integration to the integrase-mutant viral clone. Complementation experiments using purified fusion proteins in vitro, or viruses encoding a C-terminal truncated integrase and containing various fusion proteins in trans, indicated that the truncated integrase–LexA proteins are inactive per se and they restore integration by forming mixed multimers with the virally encoded mutant integrase. Correct integration of retroviral DNA by the in trans method illustrates the feasibility of introducing integrase fusion proteins into retroviral vectors to achieve site-directed integration without interfering with the attributes of the integration reaction. Fusion of wild-type or truncated integrase to a sequence-specific DNA-binding protein, such as the Escherichia coli LexA repressor, results in an integration bias toward the recognition site of the DNA-binding protein in vitro. Integrase-defective HIV-1 could become integration-competent by supplying the fusion protein in trans. To understand the mechanism of complementation, the virus–host DNA junctions of cells infected with the integrase–LexA containing virus were sequenced. The characteristic hallmarks of wild-type integration were present, a 5′-TG/CA-3′ at the ends of the viral sequence and a 5-bp direct repeat in the immediately flanking cellular DNA. Experiments were also carried out to determine the mechanism by which the amino- or carboxy-terminal truncated integrase fused to LexA restored integration to the integrase-mutant viral clone. Complementation experiments using purified fusion proteins in vitro, or viruses encoding a C-terminal truncated integrase and containing various fusion proteins in trans, indicated that the truncated integrase–LexA proteins are inactive per se and they restore integration by forming mixed multimers with the virally encoded mutant integrase. Correct integration of retroviral DNA by the in trans method illustrates the feasibility of introducing integrase fusion proteins into retroviral vectors to achieve site-directed integration without interfering with the attributes of the integration reaction.
Size of common bile duct stones on MRCP predicts likelihood of positive findings at ERCP
Authors: J. Reid, M. Patel, R. Fleming, R. Dolan, A. Hair
Journal: International Journal of Surgery (2015)

Methods:We retrospectively reviewed all the patients admitted to the RBH with a diagnosis of gallstone pancreatitis between June and December 2013.Results: Thirty patients met with the inclusion criteria but five were excluded -two were unfit for any definitive intervention, one declined it, one died prior to discharge and one was referred to a specialist paediatric unit.0/25(0%) patients underwent laparoscopic cholecystectomy with operative cholangiography and imaging of the bile ducts within the stated time-frame.7/25(28%) underwent laparoscopic cholecystectomy within the stated time-frame, but without undergoing operative cholangiography.2/25(8%) patients were considered unfit for surgery, but underwent ERCP plus sphincterotomy within the two-week time frame.Inhospital mortality rate was 1/30(6.6%)and the death resulted from complications secondary to pancreatitis.No patients died following surgical intervention.Conclusion: 70% of patients with gallstone pancreatitis did not undergo definitive treatment within the recommended timeframe.Imaging of the bile ducts, with either intra-operative cholangiography, ERCP or MRCP was not routinely performed.
Public hostility grows to private companies' expansion in the NHS
Authors: G. Iacobucci
Journal: BMJ (2013)

The UK public has become more hostile in the past two years to the idea of private providers running healthcare services, according to the results of a new poll.

The survey1 by Ipsos MORI for King’s College London asked people to agree or disagree with the statement: “As long as health services are free of charge, it doesn’t matter to me whether they are provided by the NHS or a private company.” The poll, which surveyed 1009 UK adults in October …
780 A CLINICAL STUDY ON ANTI-HBV-DC-MTL COMBINED WITH TELBIVUDINE IN THE HBeAg POSITIVE CHRONIC HEPATITIS B VIRUS INFECTION
Authors: B.-F. Wu, J.-Y. Yang, Y. Liu, X.-Q. Wang, X.-H. Huang, Z.-S. Xiao, X.-S. Li, M. Yang, Y. Zhou, J. Yang, F.-Q. Li, H. Huang, Q.-M. Qiu
Journal: Journal of Hepatology (2013)
430 PLASMA LEVELS OF CD133+ MICROPARTICLES WITH DIFFERENT EXPRESSION OF ECTONUCLEOTIDASES INDICATE MAJOR HEPATIC RESECTIONS IN MICE AND HUMANS
Authors: M. Schmelzle, C. Duhme, A. Krieg, M. Ralemska, N. Stoecklein, S. Jonas, W. Knoefel, S.C. Robson, J. Schulteam Esch
Journal: Journal of Hepatology (2012)
THU0509 Chronic Kidney Disease Independently Predicts Cardiovascular Morbidities among Hospitalized Patients with Systemic Lupus Erythematosus: Findings from a United States National Study
Authors: B. Mehta, M. Mujib, N. K. Mazumder, C. Palaniswamy, S. Khera, D. Kolte, I. Tassiulas, W. S. Aronow
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Glomerulonephritis leading to chronic kidney disease (CKD) is a major cause of morbidity in systemic lupus erythematosus (SLE). Accelerated atherosclerosis has been recognized as the major underlying factor of the early cardiovascular mortality in SLE. <h3>Objectives</h3> To investigate the associations of CKD and cardiovascular morbidities and inpatient mortality in patients with SLE from a large nationwide hospital registry database <h3>Methods</h3> All hospitalized patients aged between 18 to 65 years included in the nationwide inpatient sample (NIS) 2010 database with a confirmed discharge diagnosis of SLE, as per the ICD-9-CM code 710.0 were identified. NIS is the largest all-payer inpatient care database in the United States. Multivariable logistic regression models were used to determine the associations of CKD with congestive heart failure (CHF) and CKD with acute myocardial infarction (AMI) among these patients. Multivariable Cox proportional survival analyses were used to determine the association of CKD and in-hospital mortality. <h3>Results</h3> From 7,800,441 hospitalizations in NIS 2010 database, 28,175 SLE patients were identified. Patients had a mean age of 45 (±13) years, 90% (25,282) were women and 57% (16,186) were non-whites. CHF was prevalent in 8.6% (2302/26889) and 22.4% (288/1286) of patients without and with CKD, respectively (adjusted odds ratio for CHF comparing those without and with CKD, 2.27; 95% confidence interval {CI}, 1.96–2.64; p&lt;0.001). AMI occurred in 1.3% (360/26889) and 3.0% (38/1286) of patients without and with CKD, respectively (adjusted odds ratio, 1.53; 95% confidence interval, 1.06–2.20; p=0.023). CKD was not associated with in-hospital mortality among hospitalized SLE patients (<b>Table 1</b>). <h3>Conclusions</h3> In this large national database, CKD was independently associated with AMI and CHF among hospitalized SLE patients. However inpatient mortality was not increased. Further prospective studies are needed to understand this relationship in this high-risk population. <h3>Disclosure of Interest</h3> None Declared
Abstract 5064: The non-receptor tyrosine kinase Fer is required for activated ErbB2-mediated tumorigenesis
Authors: Waheed Sangrar, Changnian Shi, Yan Gao, Peter A. Greer
Journal: Cancer Research (2010)

Abstract The fer proto-onogene encodes a non-receptor protein-tyrosine kinase (PTK) which together with the parologous Fps/Fes kinase makes up a distinct F-BAR domain containing subclass of PTKs. F-BARs have recently been shown to mediate membrane binding and bending properties that confer roles in receptor endocytosis and vesicle trafficking. Among known substrates of the Fer PTK are cortactin and F-BAR/SH3 containing adaptor proteins that regulate cytoskeletal remodeling and membrane dynamics important to cellular functions such as polarity determination, migration and mitogenesis. Mice deficient in Fer, Fps/Fes or both kinases are overtly healthy; although they do display enhanced responses to endotoxin challenges. Biochemical studies have implicated Fer in growth factor signaling, cadherin-dependent cell-cell adhesion, integrin-mediated adhesion and redox signaling. Cell biological studies have suggested a role for Fer in potentiating proliferation and migration. Recent results in our laboratory have provided compelling biological proof-in-principle that Fer is required for mammary tumorigenesis. RNAi-based knockdown of Fer reduced the tumorigenesis of the metastatic MDA-MB-231 breast cancer cells in mouse xenografting studies. In addition, tumor development in a transgenic mouse model of Her2/Neu/ErbB2-mediated breast tumorigenesis was significantly delayed in Fer-deficient mice by virtue of a targeted knock-in kinase-inactivating mutation in the mouse fer locus. Biochemical internalization assays suggested that EGFR endocytosis was enhanced in Fer-deficient tumor-derived epithelial cell cultures. These data point to a tumor promoting function for Fer in mammary tumorigenesis through a mechanism involving prolongation of ErbB2 signaling. Taken together, these studies suggest that pharmacological intervention of Fer may have therapeutic benefit in human ErbB2 positive breast cancer and potentially, in other epithelial cancers. 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 5064.
Female "Varicocele": Two Cases Diagnosed by Labeled Red Blood Cell Angioscintigraphy and Treated by Percutaneous Phlebography and Embolization
Authors: D Gasparini, O Geatti, P G Orsolon, B Shapiro
Journal: Clinical Nuclear Medicine (1998)

Varicocele, a varicosity of the gonadal venous plexus, is a well-recognized disorder occurring in up to 10% of men. In women, an analogous varicosity of the salpingo-ovarian plexus is rare. This may be explained, in part, by the lack of obvious findings on clinical examination in women compared with men and the need, until recently, to use invasive venographic methods to confirm the diagnosis. Two cases of "female varicocele" diagnosed by means of echo Doppler and Tc-99m red blood cell scintigraphy and their cure by percutaneous phlebographic occlusion of the ovarian venous varicosity are described.
Abstract 3001: MicroRNAs regulating wnt signaling are downregulated in malignant pleural mesothelioma
Authors: Gretchen V. Gee, Devin C. Koestler, Brock C. Christensen, David J. Sugarbaker, Donatella Ugolini, Giovanni P. Ivaldi, Murray B. Resnick, E. Andreas Houseman, Karl T. Kelsey, Carmen J. Marsit
Journal: Cancer Research (2010)

Abstract Malignant pleural mesothelioma is a rapidly fatal disease whose diagnosis, particularly through less invasive techniques such as analysis of pleural effusion, can be challenging. Currently, a commercially available diagnostic test based on microRNA expression patterns is purported to distinguish between mesothelioma and lung adenocarcinoma. Yet, the biological basis of this technology has not been reported in the literature, and little research has been aimed at determining how differential miRNA expression contributes to the differences in pathogenesis between these diseases, both of which can be caused by asbestos exposure. We sought to illuminate the molecular differences between mesothelioma and lung adenocarcinoma by using microRNA microarrays to identify patterns in the most differentially expressed microRNAs. From this, we identified a panel of microRNAs, including members of the miR-200 gene family, that were all downregulated in malignant pleural mesothelioma compared to lung adenocarcinoma. Using the more sensitive detection method of quantitative RT-PCR on an independent series of tumors, we validated the specificity of these alterations in 100 malignant pleural mesotheliomas and 32 lung adenocarcinomas. Further examination of the relationship between these microRNAs revealed that they are predicted to act as redundant regulators of wnt signaling, and suggests a role for this pathway in tumor progression. This research points to novel approaches utilizing miRNAs whose decreased expression is unique to mesothelioma as potentially suitable for rapid diagnosis, and reveals important new targets for the treatment of this deadly disease. 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 3001.
Pasteurella Multocida Empyema
Authors: Harvey L. Atin, William P. Beetham
Journal: New England Journal of Medicine (1957)

PASTEURELLA multocida is a small, nonmotile, gram-negative, ovoid rod showing bipolar staining. Although it has been isolated from the respiratory and intestinal tracts of apparently normal cats, dogs, sheep, horses, fowl, swine, cattle and rats, it has long been known as the causative organism of hemorrhagic septicemia in animals.1 Human infections, though rarely reported, are probably far commoner than the literature leads one to believe.2 These infections may be of two types: a localized form resulting from an animal bite, usually that of a cat, with local abscess formation, sometimes resulting in osteomyelitis of the underlying bone; and a systemic . . .
FRI0456 Performance of magnetic resonance imaging for the detection of chronic structural changes in the sacroiliac joints as compared to conventional x-rays in axial spondyloarthritis
Authors: I. Gaydukova, K.-G. Hermann, I.-H. Song, H. Haibel, J. Braun, J. Sieper, D. Poddubnyy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Magnetic resonance imaging (MRI) is able to detect “chronic” structural changes visible on conventional X-rays. Reliability of MRI in detection of such structural changes in SIJ remains unclear. <h3>Objectives</h3> To evaluate the performance of MRI in detection of structural changes of the SIJ in comparison to conventional X-rays in patients with axial SpA. <h3>Methods</h3> 112 patients with definite axial SpA and available imaging sets consisting of an X-rays and an MRI of the SIJ were included. X-rays of the SIJ were scored according to the modified New York criteria (grade 0 to grade IV) and according to the scoring system [1], which contains scores for subchondral sclerosis (score 0-2), erosions (score 0-3), and joint space changes (score 0-5) in each SIJ. MRIs of the SIJ (T1) were scored in the similar way. X-rays and MRIs were scored by two trained readers, which were blinded for all clinical data. <h3>Results</h3> 224 SIJ from 112 patients were available. There was a rather low agreement between MRI and X-rays concerning definite erosions of SIJ (k=0.11, 95% confidence interval (CI) -0.02 to 0.23), a moderate agreement regarding definite subchondral sclerosis (k=0.46, 95% CI 0.34 to 0.57) and definite joint space abnormalities (k=0.41, 95% CI 0.28 to 0.53) and perfect agreement regarding joint ankylosis (k=0.85, 95% CI 0.74 to 0.96). MRI demonstrated good overall performance for the detection of definite “chronic” SI - figure. The sensitivity of MRI for the detection of “chronic” SI as compared to X-rays was 84% and the specificity was 61%. On the patients’ level, in 83 cases (74%), X-rays and MRI provided a unanimous conclusion regarding the presence or absence of SI fulfilling the modified New York criteria (K 0.451 (95% CI 0.280 to 0.622). The sensitivity of MRI in detection of SI fulfilling the modified New York criteria was 81%, the specificity 64%. <h3>Image/graph</h3> <h3>Conclusions</h3> MRI demonstrated good overall performance for the detection of chronic structural changes in the SIJ as compared to X-rays. <h3>References</h3> Poddubnyy D, et al. Ann Rheum Dis 2012;71(Suppl3):409. <h3>Disclosure of Interest</h3> None Declared