tbuckley/cabot-search huggingface dataset:
OC-141 Upper GI bleeding in Scotland 2000–2010: improving outcome but a significant weekend effect
Authors: A Ahmed, M Armstrong, I Robertson, O Blatchford, J Morris, A Stanley
Journal: Gut (2012)

<h3>Introduction</h3> Recent studies have suggested a reduction in incidence of upper GI haemorrhage (UGIH) and a possible worse outcome if patients present at weekends. Our aim was to assess trends in numbers and mortality of patients admitted with UGIH in Scotland and to examine whether weekend presentation affected outcome. <h3>Methods</h3> We identified 23 ICD-10 codes that identified UGIH and interrogated ISD Scotland data using these codes for the 10-year period 2000–2010. We analysed the annual numbers of patients and their 30-day mortality during this period, comparing length of stay and mortality for those admitted at weekends and weekdays. <h3>Results</h3> A total of 61 574 Scottish residents were admitted to Scottish hospitals with a diagnosis of UGIH during the years 2000/1–2009/10. There was no significant change in annual numbers of admissions during this period, but there was a reduction in 30-day mortality from 10.3% to 8.8% (p&lt;0.001). For the whole study period, patients admitted with UGIH at weekends had a higher 30-day mortality compared with those admitted on weekdays (p&lt;0.05). A significantly higher mortality for patients admitted at weekends was seen in 9 of the 10 years, including each of the last five years. This was despite patients admitted at weekends being younger than those admitted on weekdays (57.6 yrs vs 58.8 yrs; p&lt;0.001). Over the study period there was a greater length of stay for patients admitted on weekends compared with weekdays (p&lt;0.05), with the greatest difference found in the most recent year of study. <h3>Conclusion</h3> There has been a gradual reduction in mortality for patients admitted with UGIH in Scotland over the past 10 years. Despite a younger age, patients admitted at weekends had consistently higher mortality and greater length of stay compared with weekday admissions. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Button</b>, <i>et al. Aliment Pharmacol &amp;Ther</i> 2011;<b>33</b>:64–76. 2. <b>Dorn</b>, <i>et al. Dig Dis Sci</i> 2010;<b>55</b>:1658–66.
In Asian-American Women, Westernization Influences Estrogen Metabolism, but Not Total Endogenous Estrogen Production.
Authors: R. Ziegler, B. Fuhrman, X. Xu, M. Gail, L. Keefer, T. Veenstra, R. Hoover
Journal: Cancer Research (2009)

Abstract Background: Historically, breast cancer incidence rates were 4-7 times higher in the United States than in China and Japan. When Asian women migrate to the U.S., their risk rises over several generations and approaches that in U.S. Whites. Endogenous estrogen has been postulated to explain these international differences. Methods: In a population-based case-control study in Chinese, Japanese, and Filipino women living in San Francisco-Oakland, CA; Los Angeles, CA; or Oahu, HI, we documented a six-fold gradient in breast cancer risk with Westernization. Using 12-h, overnight urines from 263 premenopausal mid-luteal and 168 postmenopausal control subjects, we investigated associations of estrogens and estrogen metabolites (EM) with Westernization, particularly birthplace in the East or West. Fifteen EM were measured concurrently by liquid chromatography-tandem mass spectrometry with high accuracy, precision, and sensitivity. Log-transformed EM measures, adjusted for age and ethnicity, were compared by robust linear regression. Results: Total urinary EM (pmol/mg creatinine) was not associated with birthplace in premenopausal or postmenopausal women. When the three estrogen hydroxylation pathways were expressed as percent of total EM, the relative difference by birthplace, West compared to East, was 15% lower for 2-pathway EM (p=0.009), 7% lower for 4-pathway EM (p=0.37), and 10% higher for 16-pathway EM (p=0.008). Similar results were observed for individual EM in each pathway, premenopausal and postmenopausal women, and the three ethnicities. In both menopausal groups, 2-pathway EM concentration decreased steadily with increasing risk across six categories of Westernization. Conclusions: Our results do not indicate that total estrogen production explains the increased breast cancer risk in Western societies. However, estrogen metabolism patterns, especially reduced 2-hydroxylation, may contribute to the elevated risk; and underlying mechanisms merit further exploration. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3063.
Abstract 820: Genome-wide aberration analysis of rare cancer cell populations derived from formalin fixed paraffin embedded tissue.
Authors: Darius Juskevicius, Christian Ruiz, Tanja Dietsche, Alex Rufle, Michael T. Barrett, Lukas Bubendorf, Stephan Dirnhofer, Alexander Tzankov
Journal: Cancer Research (2013)

Abstract Introduction. The majority of clinically described patient material worldwide is available as formalin fixed parafin embedded (FFPE) tissue blocks. Despite being a cheap and convenient way of archiving tissue suitable for review under the microscope, FFPE blocks are difficult to interrogate with modern molecular biology methods due to changes occurring during the process of fixation, embedding and aging. Genetic analysis of tumours with limited malignant cell count, like classical Hodgkin lymphoma (cHL) or T-cell/histiocyte-rich B cell lymphoma (TCHRBCL) is impeded by a bulk mass of non-malignant tumour infiltrating cells. Laser capture microdissection is currently a method of choise for rare tumor cell isolation, however it induce serious damage for gDNA, therefore additional techniques for enrichment are needed to enable meaningful genome-wide aberration analysis of tumors with low cancer cell content. Methods. For extraction of nuclei from FFPE blocks of cHL and TCHRBCL cases enzymatic digestion and mechanical force were utilized. Pure populations of cancer cell nuclei were isolated by fluorescence-activated cell sorting (FACS) based on cancer type-specific nuclear markers Pax-5, Mum-1, Bcl-6, Ki-67. Array comparative genomic hybridization (aCGH) was utilized for genome-wide aberration analysis. Results. We have optimized a set of methods to successfully isolate intact, high quality nuclei from FFPE tissue blocks. Nuclei retain their antigenicity and, therefore, are suitable for labelling with frourophore-conjugarted antibodies, which enables flow-sorting based not only on physical parameters and DNA content, but also on positivity for highly specific nuclear markers. Tumour nuclei populations from cHL and TCHRBCL of 70-90% in purity were isolated. DNA extracted from as little as 500 flow-sorted nuclei was sufficient to generate high-resolution and reproducible aCGH data. Conclusions. Our proposed methodology allows the use of tissues in FFPE blocks more widely. Efficient isolation of malignant cells from the tumour mass was achieved. In the cases where starting material is scarce and very low number of target nuclei can be isolated, DNA extraction with improved recovery together with commercially available whole genome amplification methods enable genome-wide aberration analysis. Citation Format: Darius Juskevicius, Christian Ruiz, Tanja Dietsche, Alex Rufle, Michael T. Barrett, Lukas Bubendorf, Stephan Dirnhofer, Alexander Tzankov. Genome-wide aberration analysis of rare cancer cell populations derived from formalin fixed paraffin embedded tissue. [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 820. doi:10.1158/1538-7445.AM2013-820
An Efficacy Trial of Doxycycline Chemoprophylaxis against Leptospirosis
Authors: Ernest T. Takafuji, James W. Kirkpatrick, Richard N. Miller, Jerome J. Karwacki, Patrick W. Kelley, Michael R. Gray, K. Mills McNeill, Harold L. Timboe, Robert E. Kane, Jose L. Sanchez
Journal: New England Journal of Medicine (1984)

Because leptospirosis has been an important cause of morbidity in U.S. soldiers training in the Republic of Panama, we conducted a randomized, double-blind, placebo-controlled field trial during the fall of 1982 to determine whether doxycycline was an effective chemoprophylactic agent against this infection. Doxycycline (200 mg) or placebo was administered orally on a weekly basis and at the completion of training to 940 volunteers from two U.S. Army units deployed in Panama for approximately three weeks of jungle training. Twenty cases of leptospirosis occurred in the placebo group (an attack rate of 4.2 per cent), as compared with only one case in the doxycycline group (attack rate, 0.2 per cent, P less than 0.001), yielding an efficacy of 95.0 per cent. This study demonstrated the value of doxycycline as a prophylactic drug against leptospirosis.
Outcome of Invasive Lobular Carcinoma Compared to Infiltrating Ductal Carcinoma: A Population Based Study from British Columbia.
Authors: M. Al-Foheidi, C. Speers, R. Woods, H. Kennecke, H. Kennecke, S. Chia, S. Chia
Journal: Cancer Research (2009)

Abstract Background: Lobular carcinoma is the 2nd most common invasive breast cancer histology after ductal carcinoma. Though phenotypically they are different, the two histologies are often treated the same with presumed similar outcomes. We sought to compare the baseline demographics, standard pathologic factors and long term clinical outcomes between lobular and ductal carcinoma from a large population based breast cancer registry.Methods: A retrospective cohort of referred patients to the BCCA with a diagnosis of stage I-III pure lobular or pure invasive ductal carcinoma from 1989-2000 was identified. Prior or synchronous breast cancers and cases with unknown grade were excluded. Standard demographic and pathologic factors was abstracted from the BCCA Breast Cancer Outcomes Unit database and compared between the two histologies. 10 year outcomes were calculated by Kaplan Meier method, with differences compared by log rank test. Median follow up for the entire cohort was 9.3 years.Results: A total of 13,203 individual patients meeting identified inclusion criteria were identified: 11,911 invasive ductal and 1,292 invasive lobular cancers. Lobular carcinomas generally had a higher frequency of poor prognostic factors: older age (≥ 70 years old), larger tumour size, and greater frequency of N2 nodal involvement (all p&amp;lt;0.001). However lobular carcinomas also had a higher frequency of better predictive factors: ER+ status and low grade tumours (both p&amp;lt;0.001). There were differences in locoregional treatments and systemic therapies between the groups. No differences were seen at 10 year estimated relapse free survival (76% vs 74%), distant RFS (78% vs 77%), breast cancer specific survival (81% vs 81%) and overall survival (69% vs 70%) between lobular and ductal cancers respectively. Only 10 year locoregional RFS significantly favored lobular cancers (93% vs 89%; p&amp;lt;0.001), though there was also a higher mastectomy rate (55% vs 39%) in this cohort.Conclusion: Though invasive lobular carcinomas are epidemiologically and phenotypically different from ductal carcinomas, clinical outcomes are comparable between these two common histologies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2046.
THU0072 Comparison of Characteristics of Ankylosing Spondylitis in Association with Familial Mediterranean Fever with Those of Typical Ankylosing Spondylitis: Table 1.
Authors: D. Solmaz, S. Akar, B. Kisacik, S. Apras, S. Senel, A.M. Onat, T. Kasifoglu, K. Aksu, I. Sari, M.A. Ozturk, M. Sayarlioglu, A. Akdogan, P. Cetin, N. Akkoc
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Several case reports and a few published studies suggest a link between Familial Mediterranean Fever (FMF) and ankylosing spondylitis (AS). There is very limited data on the clinical features of AS that develops in patients with FMF. <h3>Objectives</h3> To compare the demographic and clinical features of patients with AS in association with FMF to patients with AS alone. <h3>Methods</h3> 73 patients with AS in co-existence with FMF (AS-FMF) who have been followed at 8 different hospitals were compared to 81 consecutive patients with AS alone. All of the patients fulfilled the modified New York criteria for AS and the patients with FMF additionally met the Livneh criteria for FMF. Patients demographic and clinical data were extracted from patients9 charts; MEFV genotypes, HLA B27 status and C reactive protein levels and radiographic results were also recorded if available. <h3>Results</h3> Patients in the AS-FMF group were younger and had a shorter disease duration. Gender distribution and age of onset of AS were similar in both groups; but diagnostic delay was longer and family history (for SpA) was reported more frequently in the AS group. Peripheral arthritis and heel enthesitis were more prevalent among AS-FMF patients whereas a higher proportion of patients in the AS group had HLA-B27 and had radiologic evidence of spinal involvement (Table). M694V allelic variation was detected in 78.7% of the patients with FMF and AS. <h3>Conclusions</h3> Clinical characteristics of AS in association with FMF may show some differences from typical AS, such as less spinal involvement. Relatively high prevalence of M694V variant among patients with FMF in coexistence with AS compared to that reported in historic cohorts of Turkish FMF patients as well as lower prevalence of HLA-B27 compared to that in AS patients may suggest that such genetic differences may also be accounted for some of the differences between the patients with AS in association with FMF and the typical AS patients. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4575
Nitrogen-Sparing Intravenous Fluids in Postoperative Patients
Authors: Herbert C. Hoover, John P. Grant, Catherine Gorschboth, Alfred S. Ketcham
Journal: New England Journal of Medicine (1975)

Improved nitrogen sparing was demonstrated in 20 patients undergoing either head-and-neck operations or abdominal explorations, who were randomized to receive intravenously either 3 per cent amino acids or 5 per cent dextrose. Infusions were started immediately after operation and continued for a minimum of six days. In patients receiving amino acids, as compared with those receiving dextrose, mean cumulative six-day nitrogen losses were significantly lower (42 ± 5 g [S.E.M. ] and 74±7g, respectively — P < 0.005), as were serum glucose and insulin levels, but β-hydroxybutyrate, acetoacetate and blood urea nitrogen were significantly elevated. No adverse effects of the amino acid solution were observed. The presumed mechanism for improved nitrogen sparing is a decrease in serum glucose and insulin levels, allowing greater endogenous fat mobilization and utilization, thus sparing lean body mass. (N Engl J Med 293:172–175,1975)
CONSISTENT BENEFIT OF SACUBITRIL/VALSARTAN OVER ENALAPRIL, IRRESPECTIVE OF BACKGROUND THERAPY IN PARADIGM-HF
Authors: Naoki Okumura, Pardeep Jhund, Jianjian Gong, Martin Lefkowitz, Adel Rizkala, Jean Rouleau, Victor Shi, Scott Solomon, Karl Swedberg, Michael Zile, Milton Packer, John J.V. McMurray
Journal: Journal of the American College of Cardiology (2016)
Fish Analysis for HEY1-NCOA2 Fusion Gene is Useful Diagnostic Tool for Mesenchymal Chondrosarcoma
Authors: K. Ono, K. Takada, R. Takimoto, T. Sato, S. Iyama, Y. Sato, M. Kobune, T. Yamashita, T. Hasegawa, J. Kato
Journal: Annals of Oncology (2013)
Abstract 1402: Molecular basis for soy isoflavone genistein in the prevention of posttreatment recurrence of neuroblastoma
Authors: Jamunarani Veeraraghavan, Rakhesh Madhusoodhanan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan
Journal: Cancer Research (2010)

Abstract Clinical and laboratory evidence suggests that neuroblastoma contain populations of rapidly proliferating clonogens that survive chemoradiation or conventional radiotherapy leading to radioresistance. To that note, radioresistance could be associated with survival advantage resulting in clonal selection and tumor re-growth. Recently, we demonstrated that IR activates NFκB that enhances cell survival by switching on genes that attenuate apoptosis. Coherently, studies have demonstrated Genistein (GEN) inhibits NFκB and radiosensitizes cancer cells. In this study, we investigated the functional mechanistic regulation of NFκB mediated survival advantage and, delineated the efficacy of GEN in this setting. Human SH-SY5Y, IMR-32 and SK-N-MC cells exposed to 2Gy (IR) with or without GEN (100μM) were examined after 15min through 72h. EMSA analysis showed a robust and persistent activation of NFκB at least up to 72h in IR exposed cells. Consistently, IR induced a sustained transactivation (QPCR) and intercellular (ELISA) TNFα in these cells. Forced inhibition of NFκB (SN50, RelA siRNA) or TNFα (TNFR1-Ab) completely and persistently inhibited IR-induced NFκB and/or TNFα demonstrating the IR-induced initiation of NFκB→TNFα→NFκB feed back mechanism (PFC). Consistently, IR simulation experiments with NFκB (SNP, p50/p65 transfection) or TNFα (rH-TNFα) over expression, persistently activated NFκB and/or TNFα exhibiting the occurrence of PFC. Furthermore, IR profoundly induced both mRNA (QPCR) and cellular localization (immunoblotting) of IAP1, IAP2 and Survivin. NFκB knock-out experiments portrait a NFκB dependent activation of IAP1, IAP2 and Survivin in these cells. Conversely, GEN treatment completely and persistently inhibited IR-induced NFκB and, both TNFα transactivation and intercellular levels. Moreover, NFκB and/or TNFα over expression studies with GEN demonstrate the disruption of PFC. In addition, GEN markedly, inhibited IR-induced NFκB dependent IAP1, IAP2 and Survivin and greatly conferred IR-induced inhibition of cell survival. Taken together these results suggests that the surviving neuroblastoma cells may result in the development of survival advantage mediated by persistent activation of NFκB through NFκB→TNFα→NFκB PFC. More importantly, disrupting IR-initiated PFC with GEN may significantly inhibit NFκB dependent survival advantage and, may serve as a potential deliverable in mitigating neuroblastoma relapse and progression after radiotherapy. Funding Support: ACS- IRG-05-066-01; Presbyterian Health Foundation 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 1402.
Abstract A27: Coordinate posttranscriptional regulation of breast cancer metastasis genes by RNA binding protein HuR
Authors: Pat Techasintana, Matthew Gubin, Joseph D. Magee, Robert Calaluce, Ulus Atasoy
Journal: Cancer Research (2011)

Abstract Breast cancer is one of the most prevalent cancers worldwide. Distance metastasis is responsible for patient mortality. Therefore, understanding the mechanisms underlying tumor pathogenesis and metastasis is crucial for the development of novel therapies as well as preventive strategies for those who are prone to breast cancer. In contrast to transcriptional gene regulation, posttranscriptional control mechanisms of gene expression are poorly understood. Yet, many metastasis genes are regulated by RNA binding proteins (RBPs) at the levels of mRNA stability and translation. The paraneoplastic antigen, HuR, is an RBP shown to regulate multiple genes that are significantly related to breast cancer metastasis by stabilizing target mRNAs and facilitating translation into proteins. Using novel techniques developed in our lab of RNA immunoprecipitation applied to microarrays (RIP-Chip) we identified novel discrete HuR-associated mRNAs in triple negative breast cancer and estrogen receptor positive breast cancer. Many of these HuR-associated mRNA transcripts were metastasis related. We investigated the role of HuR in an aggressive triple-negative breast cancer metastatic cell line, LM2. The LM2 cells were retrovirally transduced with triple fusion reporter construct encoding thymidine kinase1, GFP and firefly luciferase to obtain in vivo and in vitro tracking capabilities. The cells were further transfected with plasmid containing HA-HuR or empty vector control to demonstrate the function of HuR in LM2. HuR over-expressing clones showed greater metastatic capability by in vitro matrigel invasion assay. Furthermore, athymic mice that were intravenously injected with HuR over-expressing LM2 cells had greater (335-fold more) tumor metastasis to the lungs than empty vector control injected group as measured by IVIS imaging. Mice injected with HuR over-expressing LM2 cells were more moribund and had greater mortality as compared with mice injected with empty vector control cells. These results suggest that HuR may play a role in breast cancer metastasis by stabilizing various pro-metastatic genes. The implications of this work are twofold. First, HuR RIP-Chip can be used to identify novel cancer relevant genes and second, interference with HuR function may ameliorate distant metastasis in breast cancer, potentially providing new therapeutic approaches for treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A27.
Malformations Due to Presumed Spontaneous Mutations in Newborn Infants
Authors: K Nelson, L B Holmes
Journal: New England Journal of Medicine (1989)

We conducted hospital-based surveillance of congenital malformations to determine the rate of apparently spontaneous single mutations leading to recognized phenotypes. Through surveillance of 69,277 infants with gestational ages of at least 20 weeks, we identified 48 infants (0.07 percent) with major malformations, with phenotypes that suggested that the malformations were due to single mutant genes. Family studies suggested that 11 of these infants (10 with autosomal dominant disorders and 1 with an X-linked condition) were affected as the result of a new (spontaneous) genetic mutation. The spontaneous mutation rates per gene were 0.7 x 10(-5) and 1.44 x 10(-5) for the disorders in which one and two infants were affected, respectively. In addition, 5 of the 10 infants with autosomal recessive malformations had negative family histories, but we were unable to infer the presence of spontaneous mutations in these cases. Because the family history was negative in 44.4 percent of the infants with disorders considered due to autosomal or X-linked genes, counseling should include the understanding that genetic disorders often occur unexpectedly among children of healthy parents.