tbuckley/cabot-search huggingface dataset:
The use of an equine collagen fleece (Gentafleece®) in T1 breast cancer surgery: preliminary results.
Authors: O Buonomo, R Piccirillo, A Caramanica, R Andrich, C Tirelli, M La Pinta, F Scardamaglia
Journal: Cancer Research (2009)

Abstract Abstract #4147 Introduction: A prospective multicentric randomized study is being conduced by Breast Cancer Surgical Group of Rome in order to evaluate the benefits of the use of equine collagen (Gentafleece®) on surgical and aesthetic outcome in T1 breast cancer patients.&amp;#x2028; Materials and Methods: One hundred and sixty T1 breast cancer patients have been randomized in two groups by four Roman Institutions in order to evaluate the potential clinical benefits of the use of equine collagen and gentamicine fleece (Gentafleece®). The parameters we studied and compared into the Gentafleece® and control group were: patients'satisfaction, seroma, hematoma, infections, fibrosis and aesthetic result. Both the groups underwent clinical and Ultrasound evaluations after One, Two, and Six months.&amp;#x2028; Results: Belonging to Gentafleece® group, seroma was detected in 7 (5,6%) pts, hematoma in 4 (3,2%) cases, fibrosis and surgical suture aesthetic distortions in 14 (11,2%) pts. On the other hand, in control group were found: 20 (16%) cases of hematoma; 32 (25,6%) cases of seroma; 22 (17,6%) cases were represented by parenchimal fibrosis associated to surgical suture distortions. One case (0,8%) of so defined “reactive megalomasty” occurred in a patient previously treated by neo adjuvant chemotherapy (Gentafleece® group). One case (0,8%) of dermatitis occurred in the same group. In many cases the complete healing of surgical suture was anticipated into first Group. Infection or suture dehiscences occurred in two cases (1,6%) treated by Gentafleece® beside 13 cases (10,4%) of the control group.&amp;#x2028; Discussion: This preliminary study seems to demonstrate that Gentafleece®, equine collagen and gentamicine fleece, is able to reduce the impact of seromas, ematomas, parenchimal fibrosis and surgical sutures and parenchimal aesthetic distortions in according to collagenic properties of cicatrization and hemostatic response. Furthermore Gentafleece® affords a significative antiinfective protection against surgical infection or suture dehiscence. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4147.
SP0107 Proteomics: A Long Way from Protein Extract Towards Clinical Applications: Lessons from Osteoarthritis
Authors: C. Ruiz-Romero
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Proteomics technologies permit the simultaneous analysis of multiple targets, and have become very powerful tools in rheumatology research. In osteoarthritis (OA), accurate diagnosis at early stages and monitoring of therapeutic strategies are essential unmet needs that are being faced with proteomic strategies. In these two areas, the discovery and application of novel, non-invasive, specific biochemical markers remains to be achieved. Furthermore, ongoing research is also attempting to increase the knowledge on the complex OA pathogenesis, in order to identify novel therapeutic targets and effective drugs. According to this, proteomic analyses focused on the study of those mechanisms that play a role in OA onset and progression have led to the identification of several proteins that were not previously related with the disease. Altogether, proteomics has demonstrated in the recent years a big power for the discovery of newer protein candidates useful for early diagnosis and drug development or monitoring in OA. Considering that this disease involves several tissues and complex biological processes, combining existing biomarkers with novel protein candidates and even genetic markers appears to be a promising strategy to improve their accuracy. Nevertheless, still great efforts need to be made to impel the development of robust clinical assays that would allow the qualification and validation of those novel biomarkers that are being described by these large-scale analytical strategies before they can be employed in clinical routines. <h3>Disclosure of Interest</h3> None Declared
Risk and Prevention of Anti-factor IX Formation in AAV-Mediated Gene Transfer in the Context of a Large Deletion of F9
Authors: Paul A. Fields, Valder R. Arruda, Elina Armstrong, Kirk Chu, Federico Mingozzi, J.Nathan Hagstrom, Roland W. Herzog, Katherine A. High
Journal: Molecular Therapy (2001)

The safety of several gene therapy approaches for treatment of the severe, X-linked bleeding disorder hemophilia is currently being evaluated in early phase clinical trials. One strategy seeks to correct deficiency of functional coagulation factor IX (hemophilia B) by intramuscular (IM) administration of an adeno-associated viral (AAV) vector. A potentially serious complication of any treatment for hemophilia is formation of inhibitory antibodies against the coagulation factor protein, a risk that increases in the setting of null mutations in the factor IX gene (F9). Here, we describe hemophilia B mice with a large F9 deletion that form inhibitors within 1 to 2 months after IM administration of an AAV vector expressing mouse F9 or after repeated intravenous infusion of mouse F9 concentrate. In both cases, inhibitors are primarily IgG1 immunoglobulins representing a Th2-driven humoral immune response. We further demonstrate that anti-mouse F9 antibody formation in the gene-based approach can be reduced by transient immune modulation at the time of vector administration. Moreover, this maneuver resulted in complete absence of anti-mouse F9 and sustained expression of functional mouse F9 in some hemophilia B mice, particularly in those animals treated with the immunosuppressive drug cyclophosphamide. These data have direct relevance for design of clinical trials and strategies aimed at avoiding immune responses against a secreted transgene product.
Accuracy and concordance of endocytoscopic atypia for the diagnosis of gastric cancer
Authors: Mitsuru Kaise, Ryusuke Kimura, Kosuke Nomura, Yasutaka Kuribayashi, Daisuke Kikuchi, Toshiro Iizuka, Yasuo Ohkura
Journal: Endoscopy (2014)

<b>Background and aim:</b> High-grade atypia demonstrated by endocytoscopy may be a key criterion for the diagnosis of gastric cancer. We therefore sought to verify whether endocytoscopic atypia can provide satisfactory levels of diagnostic accuracy and concordance among trainee and expert endoscopists. <b>Method:</b> A total of 100 lesions evaluated by endocytoscopy and histopathology were enrolled to create an endocytoscopic image catalog (44 early cancers, 10 low-grade adenomas, 46 non-neoplastic lesions). Four endoscopists (two trainees and two experts) independently reviewed the catalog images and evaluated each of them for the presence or absence of endocytoscopic atypia. High-grade endocytoscopic atypia, as a criterion for cancer diagnosis, was defined as the consistent observation of any of the following features: lumen absence, lumen fusion, and irregular nuclei showing the three typical features (heterogeneous shape, swelling, and disarrangement). <b>Results:</b> High-grade endocytoscopic atypia was observed in 78 %, 18 %, and 4 % of cancers, adenomas, and non-neoplastic lesions, respectively. The sensitivity, specificity, accuracy, and positive and negative predictive values for cancer diagnosis by endocytoscopy were 78.4 %, 93.3 %, 87.3 %, 85.4 %, and 87.3 %, respectively. The concordance rate for the results of high-grade endocytoscopic atypia was good among the four endoscopists (<i>κ</i> value 0.682). No significant difference in diagnostic accuracy or concordance was observed between trainee and expert endoscopists. <b>Conclusion:</b> Using the defined high-grade atypia as a diagnostic criterion of cancer, endocytoscopy provided a satisfactory level of accuracy and concordance for the diagnosis of early gastric cancer, regardless of endoscopic expertise.
Convergence to Common Purpose in Global Health
Authors: David J. Hunter, Harvey V. Fineberg
Journal: New England Journal of Medicine (2014)

Health and disease are, to a large extent, effects of local environmental conditions, and the work of health professionals is still largely performed one patient at a time, facilitated or constrained by local resources. So does it make sense to conceptualize "global health" on a worldwide basis rather than as a patchwork of national and local jurisdictions and responses? In examining the 17 contributions to this series (concluding with the article by Gostin and Sridhar in this issue of the Journal 1), we see five major forces and trends suggesting that as the 21st century progresses, a global perspective on . . .
Minimum alcohol pricing delivers health benefits without penalising moderate drinkers, finds analysis
Authors: O. Dyer
Journal: BMJ (2013)

<h3>Abstract</h3> The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge on the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in the the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a panel of sequence-based predictors suggested the presence of multiple aggregation-prone regions in these proteomes, and revealed an enhanced aggregation propensity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone SARS-CoV-2 proteins, including the signal sequence peptide and fusion peptide 1 of the spike protein, a peptide from the NSP6 protein (NSP6-p), the ORF10 protein, and the NSP11 protein. Our results show that these peptides and proteins form aggregates via a nucleation-dependent mechanism. Moreover, we demonstrated that the aggregates of NSP11 are toxic to mammalian cell cultures. These findings provide evidence about the aggregation of proteins in the SARS-CoV-2 proteome. <h3>Significance</h3> The aggregation of proteins is linked with human disease in a variety of ways. In the case of viral infections, one could expect that the aberrant aggregation of viral proteins may damage the host cells, and also that viral particles may trigger the misfolding and aggregation of host proteins, resulting in damage to the host organism. Here we investigate the aggregation propensity of SARS-CoV-2 proteins and show that many of them can form aggregates that are potentially cytotoxic. In perspective, these results suggest that a better understanding of the effects of viruses on the human protein homeostasis system could help future therapeutic efforts.
Abstract 4134: Breast cancer antiestrogen resistance-3 promotes growth in the presence of tamoxifen through a mechanism involving p130cas and c-src
Authors: Michael S. Guerrero, Natasha R. Schuh, Amy H. Bouton
Journal: Cancer Research (2010)

Abstract Tamoxifen, an antiestrogen and estrogen receptor (ER) ligand, has been successfully used to treat ER-positive breast tumors for almost 40 years. For women with ER-positive disease, tamoxifen treatment can decrease the rate of recurrence by 50% and reduce the risk of death by 25%. Despite such success, resistance occurs in up to one-third of patients. To date, many proteins have been identified that contribute to resistance. Breast Cancer Antiestrogen Resistance-3 (BCAR3) is one such molecule; its expression induces resistance to the antiestrogens tamoxifen and ICI 182, 780 (fulvestrant). To investigate the signaling pathway(s) driving BCAR3-mediated resistance, we generated clones of the ER-positive and antiestrogen-sensitive MCF7 cell line that overexpress BCAR3 (MCF7 B6). Utilizing these cells, we show here that BCAR3 overexpression confers a growth advantage under conditions of both hormone deprivation and tamoxifen treatment. We further employed this inducible cell line to examine the relationship between BCAR3 and two other molecules that have been implicated in both antiestrogen resistance and BCAR3 signaling: the scaffold/adaptor molecule p130Cas (Cas, also known as BCAR1) and the non-receptor tyrosine kinase c-Src (Src). Upon BCAR3 overexpression, we observed an alternative Src-Cas complex, increased Src kinase activity, and an increase in Src-dependent tyrosine phosphorylation of Cas. Interestingly, these BCAR3-induced effects are preserved following tamoxifen treatment. Conversely, upon knockdown of BCAR3 in the ER-negative BT549 breast cancer cell line, Src activity was reduced, as were Cas phosphorylation and Src-Cas interactions. We also examined the expression and subcellular localization of the cyclin-dependent kinase inhibitor and known Src substrate, p27. In MCF7 B6 cells overexpressing BCAR3, we observed a decrease in the nuclear accumulation of p27 under conditions of both hormone deprivation and tamoxifen treatment. Based on these data and the established role of Src-Cas signaling in the induction of antiestrogen resistance, we postulate that these factors play a significant role in the promotion and establishment of BCAR3-mediated tamoxifen resistance. 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 4134.
Endosonographic evaluation of hypertrophied gastric folds using curved array trasducer
Authors: RA Zaydan
Journal: Endoscopy (2006)

Back ground and study aims: Hypertrophied gastric folds are frequent findings on the radiologic and endoscopic examination. Endoscopic ultrasonography (EUS) was performed for those patients to determine the diagnostic usefulness of EUS in the evaluation of hypertrophied gastric folds. Patients and Methods: Participants were 42 patients with hypertrophied gastric folds visualized by endoscopic examination. EUS was carried out by single endosonographer using curved array transducer with frequency 7.5MHz. Results: EUS examination revealed normal gastric wall thickness with intact wall layers in 20/42 patients and hypoechoic thickening of gastric wall with or without loss of echo layers in the 22/42 (16 had adnocarcinoma, 3 had lymphoma, 2 had maltoma and 1 had eosinophilic gastroenteritis). Conclusion: EUS is very usefull in the evaluation of hypertrophied gastric folds because it has excellent accuracy in the detection of abnormally thickened gastric wall, but it has limited capability in differentiation between benign and malignant condition responsible for gastric wall thickness.
Abstract 1178: Allele specific p53 mutant synthetic lethality
Authors: Xin Yu, Alexei Vazquez, Arnold J. Levine, Darren R. Carpizo
Journal: Cancer Research (2012)

Abstract Rescuing the function of mutant p53 is an attractive cancer therapeutic strategy. The NCI60 database has reported the growth inhibition of over 47,000 compounds in a panel of 60 human tumor cell lines with the p53 mutational status known. We hypothesized that we could use the NCI60 dataset as an “in silico” screen to identify compounds with activity in cell lines containing mutant p53. We identified three compounds from the thiosemicarbazone family and validated this methodology for two of the three. Both compounds demonstrate a marked sensitivity in cell lines carrying a p53-175 allele while at the same time are relatively nontoxic to cells wildtype for p53. Mechanistic studies reveal that one of the compounds restores a wildtype structure and function to the p53-175 mutant. These findings extend to p53R172H knock-in mutant mice as well as to the inhibition of xenograft tumor growth in a 175-allele specific, mutant p53 dependent manner. Together these data both validate a bioinformatics approach to the identification of compounds with activity in cell lines expressing mutant p53, and identify two compounds that demonstrate allele specific mutant p53 synthetic lethality. 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 1178. doi:1538-7445.AM2012-1178
Abstract 831: Elucidating the roles of differentially expressed microRNAs in glioblastoma multiform.
Authors: Yi Shiuan Liu
Journal: Cancer Research (2013)

Abstract To understand the roles of miRNA in the pathogenesis of glioblastoma multiform (GBM), we used the quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay to profile 29 pairs of GBM core and peripheral tissue samples. We also employed deep sequencing technology to determine the expression levels of human miRNAs in one pair of GBM samples. These studies revealed that human miRNA miR-196b was over-expressed in GBM samples. Expression levels of miR-196b in cell lines derived from GBM tumors also exhibit a grade-dependent increase. To explore the function of miR-196b in GBM, we constructed lentiviral vectors and overexpressed miR-196b in GBM cell lines. Over-expression of miR-196b enhanced cell growth and survival, promoted anchorage-independent growth and enhanced migration. To understand the targets and pathways underlying the tumor promoting activity of miR-196b, we compared gene expression patterns in control and miR-196b over-expressing cells. The cDNA microarray data were analyzed using the online GSEA Bioinformatics tools to indentify pathways altered by miR-196b. We also performed an in-house TargetScan analysis to predict and score putative miR-196b targets. Finally, results from GSEA analyses were combined with the target list which contained 700 high efficacy human miR-196b targets to identify targets of miR-196 with significant biological impact. Through these studies, we will explore the potential roles of miR-196b in the regulation of tumor suppressor genes in brain cancer by elucidating the mechanisms of direct or indirect targets and downstream related genes. Citation Format: Yi Shiuan Liu. Elucidating the roles of differentially expressed microRNAs in glioblastoma multiform. [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 831. doi:10.1158/1538-7445.AM2013-831 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
LONG-TERM EXPERIENCE WITH VASCULAR BRACHYTHERAPY FOR THE TREATMENT OF REFRACTORY DRUG-ELUTING STENT FAILURE
Authors: Smita Negi, Sarkis Kiramijyan, Edward Koifman, Hideaki Ota, Nevin Baker, Michael Lipinski, Ricardo Escarcega Alarcon, Thibault Lhermusier, Marco Magalhaes Pereira, Rebecca Torguson, William Suddath, Augusto Pichard, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2015)
Effect of HLA-A and HLA-B Matching on Survival of Grafts and Recipients after Renal Transplantation
Authors: Guido G. Persijn, Bernard Cohen, Quirijn Lansbergen, Joseph D'Amaro, Neville Selwood, Antony Wing, Jon J. van Rood
Journal: New England Journal of Medicine (1982)

Data on the effect of HLA-A and HLA-B matching between unrelated donors and recipients focus mainly on graft survival. After linking the follow-up data of the European Dialysis and Transplant Association and those of the Eurotransplant Foundation, the effect of HLA-A and HLA-B matching on recipient survival could be studied. Recipients of well-matched kidneys — i.e., without mismatches for the HLA-A and B antigens — had 51 per cent graft survival at five years, whereas recipients of grafts mismatched for four antigens had 32 per cent graft survival at five years. The overall P value between the five different mismatch classes was 0.0005. Patient survival at five years was 72 per cent in recipients of a kidney without HLA-A and B mismatches and 54 per cent in recipients of a completely mismatched donor kidney (overall, P = 0.001). These results suggest that matching for the HLA antigens has a beneficial long-term effect not only on renal-allograft survival but also on patient survival. (N Engl J Med. 1982; 307:905–8.)
AB0629 A critical appraisal of the competence of crystal identification by rheumatologists.
Authors: D. Berendsen, T. L. Jansen, W. Taylor, T. Neogi, J. Fransen, E. Pascual, H. R. Schumacher, N. Dalbeth
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The gold standard for diagnosing crystal arthritis is aspiration of synovial fluid and subsequent polarized microscopy on the punctured fluid. However, various studies have shown a lack of consistency in results of crystal analysis among different observers. We have proposed to certify dedicated colleagues by confirming skill of crystal identification and to increase our insight in general about expertise with the identification of crystals in synovial fluid. By obtaining these data concerning current microscopical performance, we aim to find areas of crystal recognition which are open for further improvement. <h3>Objectives</h3> The primary objective is to confirm the expertise of physicians with the identification of crystals in synovial fluid/tissue. An online test prepared for the Study of Updated Gout criteria: acr/eulaR (SugaR) emphasizes the recognition of monosodium urate (MSU) crystals, plus the identification of a predefined set as non-MSU crystals; this online test also includes identification of other crystals, such as calcium pyrophosphate dihydrate (CPP), cholesterol, oxalate and apatite. Our secondary objective is to find out whether observer factors are related to microscopical performance. <h3>Methods</h3> Diagnosticians from different countries, who are working in the rheumatology field and performing microscopic analysis were asked to participate to qualify for entrance to the SugaR Study. The first part of the test included a number of questions concerning personal/professional data. The second part contained 30 slides with images of crystals and other look-a-likes from synovial fluid: crystals shown were 8 MSU, 5 CPP, 4 cholesterol, 2 oxalate and 1 apatite. The test also included slides with potentially confusing look-a-likes. <h3>Results</h3> Up to January 1st 2013, 56 persons performed the online test; 46% (n=43) of them identified each one of the 20 crystals correctly. With respect to MSU crystals 77% identified 8 MSU crystals, 91% identified at least 7 out of 8 MSU crystals; 68% of all attendees identified 5 CPP crystals and 91% at least 4 out of 5 CPP crystals. See table. Ability to recognize crystals when they are there (%) <h3>Conclusions</h3> Almost half of the attendees performed well at identifying a diversity of crystals: MSU crystals appeared easier to identify than CPP. The objective performance regarding crystal identification can be improved in all. There seems to be no clear relationship between confidence of expertise and actual expertise. <h3>Disclosure of Interest</h3> None Declared