tbuckley/cabot-search huggingface dataset:
PWE-129 Trends In Variceal Bleeding: A Single Centre Experience From 2006–2013
Authors: C Grant, D Kemp, M Beattie, A Austin
Journal: Gut (2014)

Competitive antagonists to nicotinic acetylcholine receptors are clinically used as muscle relaxants. Previously, we reported the kinetics of inhibition (in the absence of acetylcholine) by (+)-tubocurarine and pancuronium on embryonic receptors. Here, we examine cisatracurium, a commonly used muscle relaxant. Outside-out patches were equilibrated with cisatracurium before application of 300 μM acetylcholine. cisatracurium inhibited the initial peak current, but the decay of these currents displayed a pronounced biphasic behavior. The IC<sub>50</sub> value was 54 ± 2 nM and 115 ± 4 nM for adult and embryonic receptors, respectively. We designed a rapid perfusion system to apply or remove cisatracurium for various times before application of acetylcholine. We determined the association (embryonic, 3.4 ± 0.4 × 10<sup>8</sup> M<sup>−1</sup> s<sup>−1</sup>; adult, 1.8 ± 0.3 × 10<sup>8</sup> M<sup>−1</sup> s<sup>−1</sup>) and dissociation (embryonic, 34 ± 6/s; adult: 13 ± 5/s) rates for cisatracurium. Association was 2.9- and 1.3-fold greater than that of (+)-tubocurarine and pancuronium, respectively. Dissociation was 6- and 16-fold higher than (+)-tubocurarine and pancuronium, respectively. These measurements correspond to dissociation of cisatracurium from receptors in the absence of acetylcholine. Physiologically, acetylcholine interacts with receptors equilibrated with antagonist. We developed a mathematical technique that removes the effect of desensitization and determined dissociation (embryonic, 52 ± 9/s; adult, 33 ± 5/s) in the presence of acetylcholine. These data suggest that presence of acetylcholine on one binding site of the receptor increases the dissociation rate of antagonist from the other binding site. We incorporated all of these rates into a computer simulation of a comprehensive 11-state Markov model. There was excellent agreement (without curve fitting) between simulated and experimental currents.
Hackers demand ransom to release encrypted US medical records
Authors: Owen Dyer
Journal: BMJ (2016)

Hackers have shut down the computers of MedStar, the principal healthcare provider in Washington, DC, and surrounding areas, and are warning that millions of medical records will be lost forever 10 days hence if the healthcare group does not pay a ransom of 45 bitcoins, roughly $19 000 (£13 000; €16 500).

It is the third attack by “ransomware” hackers on US hospitals in recent weeks, and the highly vulnerable industry, known for poor computer security, fears that it could signal a new trend.

Screens went dark at all of MedStar’s 10 hospitals and 250 outpatient clinics throughout Washington, Maryland, and Virginia when the group shut down its own systems in an unsuccessful attempt to prevent …
Abstract LB-312: Methylated RASSF1a is the first specific DNA marker for minimal residual disease testing in neuroblastoma
Authors: Janine Stutterheim, Fatima Ait Ichou, Emmy den Ouden, Rogier Versteeg, Huib N. Caron, Godelieve A.M. Tytgat, C. Ellen van der Schoot
Journal: Cancer Research (2011)

Abstract Purpose PCR-based detection of minimal residual disease (MRD) in neuroblastoma is presently based on neuroblastoma-specific transcripts. However, the expression of these targets varies between patients and upon treatment, and only PHOX2B is truly specific. RASSF1a is methylated (RASSF1aM) in neuroblastoma and we investigated whether it can serve as a specific and stable DNA MRD marker. Patients and methods The RASSF1aM specific real-time quantitative (RQ)-PCR was tested on control bone marrow (BM) (n=50), on 71 neuroblastoma tumors and on 159 clinical BM samples at diagnosis and at follow up of 77 patients. Results were compared to a panel of RNA markers and correlated with prognosis. Results RASSF1aM was present in all stage 4 and 4s tumors (n=50) and in 86% stage 1–3 tumors (n=21). The level of methylation in stage 4 neuroblastoma was correlated with overall survival (p=0.02). RASSF1aM-PCR was highly specific (only one amplification in 50 control samples tested in triplicate) and had a similar sensitivity as the RNA-based PCRs as shown on clinical samples. Moreover, RASSF1aM enabled accurate quantification without need for the original tumor. Conclusion RASSF1aM is a novel, highly specific DNA marker for MRD detection in neuroblastoma, equal to PHOX2B in specificity and sensitivity, and better suitable for MRD quantification. We propose to include RASSF1aM in further prospective MRD studies in neuroblastoma alongside RNA MRD markers. In addition, this assay can be used for sensitive detection and quantification of circulating cells in all cancers with hypermethylated RASSF1a. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-312. doi:10.1158/1538-7445.AM2011-LB-312
Phenotypic Comparison of B cells in Discordant Identical Twins with Common Variable Immunodeficiency and Recurrent Sino-Pulmonary Infection Patients
Authors: T.A. Hwangpo, E. Szymanska, C.R. Liu, M.G. Brand, E.E. Brown, H. Schroeder
Journal: Journal of Allergy and Clinical Immunology (2012)
Demonstration of Spinal Osteomyelitis With Ga-67 Citrate, Tc-99m MDP, and Tc-99m Ciprofloxacin With Provisionally Negative Results on MRI
Authors: S Jayaraman, A M Al-Nahhas, G Vivian, T J Gilbert, P M Hughes
Journal: Clinical Nuclear Medicine (2000)

A 65-year-old woman was hospitalized with pyrexia and lumbar back pain. Radiographs of her lumbar spine and MRI were performed on the day of admission and the results were considered normal. Five days after admission, a Tc-99m MDP bone scan was performed and showed nonspecific increased uptake at L2–L3. Planar and SPECT Ga-67 citrate scintigraphy showed increased tracer uptake at L2–L3. MRI confirmed osteomyelitis at this site. A Tc-99m ciprofloxacin scan was performed and also showed infection at L2–L3. Group B Streptococcus grew in blood cultures from the patient, who improved clinically after a prolonged course of antibiotics.
Abstract 5661: Pharmaceutically controlled replication of adenoviruses in mesenchymal stem cell-based cell carriers improves oncolytic virotherapy for advanced human renal cell carcinoma
Authors: Wan-Chi Hsiao, Chia-Hui Liao, Shian-Ying Sung, Chia-Ling Hsieh
Journal: Cancer Research (2012)

Abstract Cell-based carriers were recently exploited as a tumor-targeting tool to improve systemic delivery of oncolytic viruses for cancer therapy. However, the slow clearance of carrier cells from normal organs indicates the need for a controllable system which allows viral delivery only when the carrier cells reach the tumor site. In this communication, we sought to develop a pharmaceutically-inducible cell-based oncolytic adenovirus delivery strategy for effective targeting and treatment of renal cell carcinoma (RCC), which is one of the most malignant tumor types with an unfavorable prognosis. Herein, we demonstrated the intrinsic tumor homing property of human bone marrow-derived mesenchymal stem cells (hMSCs) to specifically localize primary and metastatic RCC tumors after systemic administration in a clinically relevant orthotopic animal model. PDGF-AA secreted from RCC was identified as a chemoattractant responsible for the recruitment of hMSCs. Like endogenous osteocalcin whose barely detectable level of expression was dramatically induced by vitamin D3, the silenced replication of human osteocalcin promoter-directed Ad-hOC-E1 oncolytic adenoviruses loaded in hMSCs was rapidly activated and the released viral progenies sequentially killed co-cultured RCC cells upon vitamin D3 exposure. Moreover, systemic treatment of RCC tumor-bearing mice with Ad-hOC-E1-loaded hMSCs had very limited effect on tumor growth, but when it combined with vitamin D3 treatment induced effective viral delivery to RCC tumors and significant tumor regression. Therapeutic effects of hMSC-based Ad-hOC-E1 delivery were confirmed to be significantly greater than those of injection of carrier-free Ad-hOC-E1. Our results presented the first pre-clinical demonstration of a novel controllable cell-based gene delivery strategy that combines the advantages of tumor tropism and vitamin D3-regulatable human osteocalcin promoter-directed gene expression of hMSCs to improve oncolytic virotherapy for advanced RCC. 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 5661. doi:1538-7445.AM2012-5661
Abstract B17: Stepwise prostate carcinogenesis <i>in vitro</i> culture
Authors: Xisong Ke, Wencheng Li, Yi Qu, Randi Hovland, Varda Rotter, Lars A. Akslen, Anne Margrete Øyan, Karl-Henning Kalland
Journal: Cancer Research (2009)

Abstract The loss of epithelial characteristics and the acquisition of a migratory phenotype, referred to as epithelial to mesenchymal transition (EMT), is a crucial event in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to mesenchymal cells (EPT1) without malignant transformation. To achieve transformed prostate cells, EPT1 cells were kept growing in extended saturation density culture to select for cells overriding quiescence. Many foci formed in EPT1 monolayers after 4 weeks at confluence, but foci never appeared in EP156T monolayers in parallel controls. Cells from the foci formed robust colonies in soft agar suggesting full malignant transformation. The transformed cells were named EPT2. In this stepwise transformation model, EPT2 cells showed much higher abilities to proliferation at confluence, migrated better and were less dependent on exogenous growth factors than EP156T and EPT1 cells. Foci were more easily derived from EPT1 cells at later passages following EMT. Gene expression profiling showed progressive downregulation of CDH1 from EP156T, through EPT1 to EPT2 together with a number of additional changes. Our findings provide a novel stepwise transformation model according to which EMT can occur independently of transformation, but can promote subsequent malignant transformation in prostate carcinogenesis. Citation Information: Cancer Res 2009;69(23 Suppl):B17.
SAT0312 Psoriasis and psoriatic arthritis among natives and mestizos from the andean mountains region of peru
Authors: S.M.A. Toloza, O. Vega-Hinojosa, V. Chandran, R. Valle-Oñate, L.R. Espinoza
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous epidemiological studies described that both Psoriasis (Ps) and Psoriatic Arthritis (PsA) are diseases with negligible prevalence among Natives from the Andean mountains of Peru. We herein first report the presence of Ps and PsA as well as the clinical status of Peruvian Natives and Mestizos with psoriatic disease. <h3>Objectives</h3> Our purpose was to describe the most salient demographic and clinical features of Peruvian Natives and Mestizos with Ps and PsA from Juliaca, Puno in the Andean mountains region of Peru. <h3>Methods</h3> During October 1st 2008 to December 31st 2010 consecutive patients attending the rheumatology clinic at the Hospital III in Juliaca, Puno (Southern Peru) at 3824 meters above sea level were carefully assessed for the presence of PsA satisfying the CASPAR classification criteria. The diagnosis of Ps was confirmed by a dermatologist. Descriptive statistics were used to describe the study population. <h3>Results</h3> Twelve patients with a mean (SD) age of 49.3 (10.7) years fullfilling CASPAR classification criteria were identified. There were 7 (58%) men and 5 (42%) women. 7 PsA patients were Natives of Quechua Ancestry and 5 Mestizos of European and Quechua mix. The main demographic and clinical features of the two ethnic groups included are summarized in table. At the time of first clinical visit all Natives with PsA had no family history of both Ps and PsA and exhibited an established disease (ranging from 12-72 months), were more likely to have a polyarticular disease, and a more severe disease phenotype evidenced by the presence of radiographic damage than Mestizos with PsA. Methotrexate exposure (dose ranging from 15-20 mg/wk) was almost universal in both Natives and Mestizos as was the absence of exposure to biological agents in spite of radiographic damage. <h3>Conclusions</h3> We first report Ps and PsA in the absence of a family history among Natives of the Andean Mountains of Peru in whom the CASPAR criteria was successfully applied to classify PsA patients. At the time of first visit PsA among the indigenous appeared to be chronic and more severe as most of these patients had radiographic damage. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-34: Targeted delivery of siRNAs to diverse solid cancers by a novel immunoconjugate comprising tetrameric human protamine linked to an internalizing anti-TROP-2 humanized antibody
Authors: Pankaj Gupta, David M. Goldenberg, Chien-Hsing Chang
Journal: Cancer Research (2010)

Abstract Despite the potential of RNA interference (RNAi) to silence specific genes, the full therapeutic potential of RNAi remains to be realized due to the lack of an effective delivery system to target cells in vivo. To address this critical need and prompted by the promising results obtained with fusion proteins comprising the nucleic-acid-binding human protamine and a cell-targeting Fab or scFv, we have developed novel immunoconjugates having multiple copies of human protamine tethered to a tumor-targeting, internalizing antibody for targeted delivery of siRNAs in vivo. The Dock-and-Lock (DNL) method developed by us provides the design and strategy for building such multifunctional agents. DNL enables site-specific, self-assembly of two modular components with each other, resulting in a stable covalent structure of defined composition with retained bioactivity. The basic strategy of DNL involves the generation of two types of modules, one containing the dimerization and docking domain (DDD) of cAMP-dependent protein kinase (PKA) and the other containing the anchoring domain (AD) of a related A-kinase anchoring protein (AKAP). Docking a DDD-containing module with an AD-containing module occurs spontaneously, and the resulting complex is locked with disulfide bonds to enhance in vivo stability. We generated DDD2-L-thP1, a DDD-module of truncated human protamine (thP1, residues 8 to 29 of full human protamine 1), in which the sequences of DDD2 and thP1 are fused to the light chain of a humanized antibody at the N- and C-termini, respectively. The reaction of DDD2-L-thP1 under mild redox conditions with hRS7-IgG-AD2, an AD-module derived from an anti-TROP-2, internalizing, humanized antibody, resulted in the facile formation of the desirable DNL complex, designated E1-L-thP1, which contains four copies of thP1 appended to the carboxyl termini of the heavy chains. The purity and molecular integrity of E1-L-thP1 following Protein A purification was shown by size-exclusion HPLC and SDS-PAGE. In addition, the ability of E1-L-thP1 to bind plasmid DNA or siRNAs was demonstrated by the gel shift assay. E1-L-thP1 was effective in protecting the bound DNA from digestion by nucleases added to the sample or present in serum, and its function to carry siRNAs into TROP-2 expressing cancer cells was confirmed by fluorescence microscopy using FITC-conjugated siRNAs and the human lung cancer cell line, Calu-3. Further evaluation of the in vitro and in vivo efficacy of E1-L-thP1 for delivery of CD74-specific siRNAs to treat TROP-2 expressing pancreatic cancer is ongoing. 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 LB-34.
THU0479-HPR What do we know about self-reported fatigue in systemic lupus erythematosus?
Authors: S. Clenathous, M. Tyagi, D. Isenberg, S. Newman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fatigue is one of the most complex and ill understood symptoms of chronic illness often reported as the number one complaint by patients with systemic lupus erythematosus (SLE). <h3>Objectives</h3> This paper aims to provide a comprehensive review of the literature of fatigue in SLE and more specifically to examine the literature regarding: a) The measurement, prevalence and nature of fatigue in SLE b) The role of disease variables and comorbid conditions in relation to fatigue in SLE c) the association of psychosocial variables with fatigue in SLE d) the effectiveness of non-pharmacological interventions for fatigue in SLE <h3>Methods</h3> Electronic searches were performed on 6 databases including AMED, Cinahl, EMBASE, Medline, PsychINFO and PubMed. Primary reference lists of retrieved articles were scanned for any potentially relevant papers. Studies were selected for review if they were reviewing a formally diagnosed SLE sample and utilised a fatigue-specific measure. <h3>Results</h3> Fatigue was assessed by a range of self-report instruments, the content of which varies significantly. The results displayed a consensus on the high prevelance of fatigue in SLE, which is significantly higher when compared to controls. The aetiology of fatigue appears to be multifactorial. Disease activity and other disease related variables (e.g. organ damage &amp; disease duration) are not always significantly associated with fatigue, in comparison with other secondary features of SLE (e.g. sleep difficulties, pain &amp; physical deconditioning) and psychological variables. There is some evidence to suggest the potential of non-pharmacological interventions in reducing fatigue in SLE. <h3>Conclusions</h3> The literature is limited by the cross-sectional nature of most of the studies that do not permit for any firm conclusion regarding the direction of causal relationships to be made. The high prevalence of fatigue in SLE emphasises the need for further detailed prospective research to inform the understanding of its aetiology, course, and management. <h3>Disclosure of Interest</h3> None Declared
PREVALENCE OF CHLAMYDOPHILA PSITTACI AND BORRELIA BURGDORFERI INFECTIONS IN A SERIES OF 108 PRIMARY CUTANEOUS LYMPHOMAS
Authors: S. Mappa, S. Govi, E. Pasini, A. J. Ferreri, M. Ponzoni, F. Facchetti, C. Doglioni, E. Berti, R. Dolcetti
Journal: Annals of Oncology (2011)
Abstract 5127: Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion
Authors: SiYi Hu, Nathalie Delorme, Zhenzhen Liu, Tao Liu, Cruz Velasco-Gonzalez, Jone Garai, Ashok Pullikuth, Shahriar Koochekpour
Journal: Cancer Research (2010)

Abstract Factors responsible for invasive and metastatic progression of prostate cancer (PCa) remain largely unknown. Previously, we reported cloning of prosaposin (PSAP) and its genomic amplification and/or overexpression in several androgen-independent metastatic PCa cell lines and lymph node metastases. PSAP is the lysosomal precursor of saposins, which serve as activators for lysosomal hydrolases involved in the degradation of ceramide (Cer) and other sphingolipids. Our current data show that, in metastatic PCa cells, stable down-modulation of PSAP by RNA-interference via a lysosomal proteolysis-dependent pathway decreased β1A-integrin expression, its cell-surface clustering, and adhesion to basement membrane proteins; led to disassembly of focal adhesion complex; and decreased phosphorylative activity of focal adhesion kinase and its downstream adaptor molecule, paxillin. Cathepsin D (CathD) expression and proteolytic activity, migration, and invasion were also significantly decreased in PSAP knock-down cells. Transient-transfection studies with β1A integrin- or CathD-siRNA oligos confirmed the cause and effect relationship between PSAP and CathD or PSAP and Cer-β1A integrin, regulating PCa cell migration and invasion. Our findings suggest that by a coordinated regulation of Cer levels, CathD and β1A-integrin expression, and attenuation of “inside-out” integrin-signaling pathway, PSAP is involved in PCa invasion and therefore might be used as a molecular target for PCa therapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5127.
GMC to cut investigations to reduce stress on doctors
Authors: Clare Dyer
Journal: BMJ (2016)

The UK General Medical Council plans to cut the number of full investigations it carries out, as part of a comprehensive package to reduce stress on doctors who have complaints made against them.1

More cases will be screened out after early inquiries, rather than proceeding to a full investigation, and more concerns will be dealt with locally by a doctor’s employer.

The changes follow recommendations by Louis Appleby, professor of psychiatry at the University of Manchester, who was appointed by the UK medical regulator last December to review its fitness to practise …
Accidental Finding on Bone Scan
Authors: Rafid Kakel, Paula Kennedy, Johan Booysen
Journal: Clinical Nuclear Medicine (2012)

Cleft sternum is an extremely rare anomaly of development. It results from failure of fusion of midline structures that contribute to the formation of the sternum. The defect may affect the upper sternum, the lower sternum, or the whole sternum. Most cases are diagnosed in childhood when it is associated with serious midline defects. We present a case of an isolated upper sternal cleft in a 55-year-old adult, found accidentally on bone scan. To our knowledge, no bone scan image of cleft sternum could be found in the literature.
1284 THE PPARg GENE EXPRESSION IS REGULATED BY THE KR ÜPPEL-LIKE TRANSCRIPTION FACTORS (KLFS) UNDER STEATOTIC CONDITIONS
Authors: C. Pérez-Monter, I. Escalona-Nandez, A. Estanez-Herna'ndez, V. Ortiz, D. Guerrero-Escalera, A. Tovar-Palacio, M. Uribe- Esquivel
Journal: Journal of Hepatology (2013)
10 Years of Progress in Chronic Myelogenous Leukemia
Authors: Elias Jabbour, Michael S. Mathisen, Susan O’Brien
Journal: Journal of the National Comprehensive Cancer Network (2012)

Jabbour is actively involved in research in both acute and chronic forms of leukemia.He was actively involved in clinical trials that lead to the approval of several drugs in chronic myeloid leukemia (CML) and myelodysplastic syndromes.His research on resistance to imatinib and mutations of the protein kinase domain were presented in several international meetings and published in peer-reviewed journals.He is also developing tailored therapies to CML.The ideas and viewpoints expressed in this editorial are those of the author and do not necessarily represent any policy, position, or program of NCCN.
Geographic Favoritism in Liver Transplantation — Unfortunate or Unfair?
Authors: P A Ubel, A L Caplan
Journal: New England Journal of Medicine (1998)

Donna Shalala, secretary of the Department of Health and Human Services, recently proposed regulations that would fundamentally change the way in which cadaveric livers for transplantation are allocated in the United States. Currently, livers are distributed first according to geographic region and then according to medical criteria. As a result, patients' chances of living or dying are shaped more by where they live than by how urgently they need a transplant. This system also allows some patients to increase their odds of receiving an organ by listing themselves at more than one transplantation center in different regions, a practice known . . .