tbuckley/cabot-search huggingface dataset:
Abstract 4967: Changes in c-Myb specificity and activities during the cell cycle in T-ALL and AML
Authors: Anita M. Quintana, Janeth J. Pena, Scott A. Ness
Journal: Cancer Research (2010)

Abstract The c-Myb transcription factor is a critical regulator of proliferation and stem cell differentiation, and mutated alleles of c-Myb are oncogenic, but little is known about the activities of c-Myb during the cell cycle. Previous studies showed that c-Myb interacts with the cell cycle regulators Cyclin D1 and Cyclin Dependent Kinases 4 and 6, suggesting that c-Myb activity is regulated during the cell cycle. We set out to test that directly, using Chromatin ImmunoPrecipitation (ChIP) assays capable of assessing the activities of c-Myb in primary and flow sorted populations of cells. We performed ChIP assays with cells sorted into each phase of the cell cycle to determine c-Myb specificity and correlated c-Myb occupancy with the relative expression of a number of known target genes. Briefly, asynchronously growing cells were fixed, stained with Hoechst 33342, then flow-sorted into different cell cycle phase populations before processing the samples for ChIP assays. The c-Myb protein associated with different cyclin gene promoters in different stages of the cell cycle, showing that c-Myb specificity and activity are dynamic. By using several different anti-Myb antibodies, we confirmed that the changes were due to relocalization of c-Myb, and not due to changes in the accessibility of individual epitopes. We also analyzed the Myb-regulated CXCR4 gene promoter in both primary AML and Jurkat T-ALL cells. c-Myb occupied the CXCR4 gene promoter during S and G2/M phase of the cell cycle, which correlated with increased CXCR4 expression in cycling cells. In conclusion, our data demonstrate that c-Myb specificity is dynamic, that c-Myb associates with different genes in different phases of the cell cycle and that c-Myb is cell cycle regulated in both T-ALL and primary human AML. 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 4967.
Abstract 281: Prevalence of Human papilloma virus in oral squamous cell carcinoma using Liner Array HPV genotyping kit
Authors: Keisuke Ohno, Keisuke Sugahara, Akira Katakura, Homare Kawachi
Journal: Cancer Research (2011)

Abstract Background. The major risk factors for oral squamous cell carcinoma (OSCC) are cigarette smoking, alcohol consumption, and betel quid chewing. In addition, human papillomavirus (HPV) infection has been associated with some OSCC. However, the relationships of HPVs to OSCCs remain unclear because of the difficulties in interpreting studies that demonstrate various prevalence rates of HPVs. We examined the prevalence of HPV in OSCCs. For HPV detection and genotyping, a sensitive and specific PCR-based method, the Roche Linear Array HPV genotyping kit test was used for these studies. Materials and Methods. Forty-five Japanese patients with OSCC were included in the present study. Surgical resection of primary tumors and normal tissues from all patients was performed at the Hospital of Tokyo Dental College, between December 2007 and December 2010. We assessed HPV infection in OSCC patients using the Roche Liner Array HPV genotyping Test, which can detect 37 different HPV types. Results. HPV was detected in 9 OSCC patients (20%). HPV subtype 39, 42 was the most prevalent type, but other types detected included 31, 33, 45 . . . high-risk types and 3, 6, 8 . . . low-risk types. Conclusion. The Roche Liner Array HPV genotyping Test is currently used as a standardized diagnostic test for HPV detection in cervical carcinoma in Europe. Some studies have shown that the most prevalent HPV subtype was the high-risk type HPV-16, However we showed that HPV is detected multiple type involved low- and high-risk type in oral carcinoma. We suggested that multiple subtypes of HPV implicated OSCC. 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 281. doi:10.1158/1538-7445.AM2011-281
Quasi-Experimental Evaluation of the Effectiveness of a Large-Scale Readmission Reduction Program
Authors: Grace Y. Jenq, Margaret M. Doyle, Beverly M. Belton, Jeph Herrin, Leora I. Horwitz
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Feasibility, effectiveness, and sustainability of large-scale readmission reduction efforts are uncertain. The Greater New Haven Coalition for Safe Transitions and Readmission Reductions was funded by the Center for Medicare &amp; Medicaid Services (CMS) to reduce readmissions among all discharged Medicare fee-for-service (FFS) patients. <h3>Objective</h3> To evaluate whether overall Medicare FFS readmissions were reduced through an intervention applied to high-risk discharge patients. <h3>Design, Setting, and Participants</h3> This quasi-experimental evaluation took place at an urban academic medical center. Target discharge patients were older than 64 years with Medicare FFS insurance, residing in nearby zip codes, and discharged alive to home or facility and not against medical advice or to hospice; control discharge patients were older than 54 years with the same zip codes and discharge disposition but without Medicare FFS insurance if older than 64 years. High-risk target discharge patients were selectively enrolled in the program. <h3>Interventions</h3> Personalized transitional care, including education, medication reconciliation, follow-up telephone calls, and linkage to community resources. <h3>Measurements</h3> We measured the 30-day unplanned same-hospital readmission rates in the baseline period (May 1, 2011, through April 30, 2012) and intervention period (October 1, 2012, through May 31, 2014). <h3>Results</h3> We enrolled 10 621 (58.3%) of 18 223 target discharge patients (73.9% of discharge patients screened as high risk) and included all target discharge patients in the analysis. The mean (SD) age of the target discharge patients was 79.7 (8.8) years. The adjusted readmission rate decreased from 21.5% to 19.5% in the target population and from 21.1% to 21.0% in the control population, a relative reduction of 9.3%. The number needed to treat to avoid 1 readmission was 50. In a difference-in-differences analysis using a logistic regression model, the odds of readmission in the target population decreased significantly more than that of the control population in the intervention period (odds ratio, 0.90; 95% CI, 0.83-0.99;<i>P</i> = .03). In a comparative interrupted time series analysis of the difference in monthly adjusted admission rates, the target population decreased an absolute −3.09 (95% CI, −6.47 to 0.29;<i>P</i> = .07) relative to the control population, a similar but nonsignificant effect. <h3>Conclusions and Relevance</h3> This large-scale readmission reduction program reduced readmissions by 9.3% among the full population targeted by the CMS despite being delivered only to high-risk patients. However, it did not achieve the goal reduction set by the CMS.
Molecular Basis of the Long-QT Syndrome Associated with Deafness
Authors: Igor Splawski, Katherine W. Timothy, G. Michael Vincent, Donald L. Atkinson, Mark T. Keating
Journal: New England Journal of Medicine (1997)

In 1957, Jervell and Lange-Nielsen reported a syndrome of congenital sensory deafness associated with a prolonged QT interval in four children of a Norwegian family.1 The affected children had multiple syncopal episodes, and three died suddenly at the ages of four, five, and nine years. Since 1957, other examples of the long-QT syndrome associated with deafness (the Jervell and Lange-Nielsen syndrome) have been described.2–4 In all cases, the apparent mode of inheritance was autosomal recessive. This syndrome is rare (estimated incidence, 1.6 to 6 cases per million).2 Affected persons are susceptible to recurrent syncope, and they have a high . . .
Abstract LB-181: Piperlongumine inhibits growth and survival of human Burkitt lymphoma by downregulating NF-κB, c-Myc and LMP1
Authors: Seong-Su Han, Dong-Ju Son, Hwakyung Yun, Siegfried Janz
Journal: Cancer Research (2012)

Abstract Piperlongumine (PL), a natural product constituent of the fruit of the Long pepper, Piper longum, has well documented anti-inflammatory and cancer inhibiting properties. The latter include evidence that PL selectively kills solid tumor cells, but spares their normal counterparts. Because it has not been established whether PL can also inhibit hematological malignancies of the B-lymphocyte lineage, we here decided to evaluate the efficacy with which PL suppresses growth and survival of human non-Hodgkin's Burkitt lymphoma (BL) cells in vitro. We found that PL curbed cell growth (IC50 values of PL for 24h treatment: DG-75; 8.5uM, Daudi; 2.84uM, Raji; 7.7uM and Ramos; 4.5uM) and caused Caspase-3-dependent apoptosis of BL cells in a concentration- and time-dependent manner. PL strongly suppressed constitutive NF-κB signaling by inhibition of IκBα degradation and subsequent nuclear translocation of p65 as well as interruption of NF-κB binding to its consensus DNA sequence. PL also disrupted the expression of NF-κB target genes such as E2F1, c-Myb and GADD45B. c-Myc, transcription factor important for BL development and survival, was remarkably reduced after treatment with PL. In EBV-positive BL cell lines that express high level of LMP1 (e.g., Daudi, Raji), PL efficiently repressed LMP1, a known activator of NF-κB. Considering that NF-κB, c-Myc and LMP1 play important roles in the development and in vivo maintenance of B-lineage and other types of blood cells neoplasms, our findings strongly suggest that PL may afford new approaches to the chemoprevention and treatment of blood cancers. 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 LB-181. doi:1538-7445.AM2012-LB-181
The role of FDG-PET for preoperative evaluation of regional lymph node metastases in locally advanced breast cancer.
Authors: J Seo, B Son, S An
Journal: Cancer Research (2009)

Abstract Abstract #4021 Backgound: The aim of this study was to evaluate the role of FDG-PET in detecting regional lymph node metastases in locally advanced breast cancer.&amp;#x2028; Methods: FDG-PET was performed in 114 women with locally advanced breast cancer. Among them, 7 were with primary tumor larger than 5cm, 18 were with inflammatory breast cancer, and 89 were with clinically palpable axillary lymph node metastases. FDG uptakes of axillary, internal mammary, and supraclavicular lymph node were correlated by comparing pathologic and radiographic findings.&amp;#x2028; Results: The sensitivity, specificity, and positive predictive value of FDG-PET for detection of axillary lymph node metastases in 83 patients who did not receive neoadjuvant chemotherapy were 91%, 33.3 % and 94.7% respectively. Among the 83 patients, 4 were with false-negative and 6 were with false-positive. Those for detection of axillary lymph node metastases in 12 patients who received neoadjuvant chemotherapy were 55.6%, 100%, and 100% respectively, and 4 of them were with false-negative and no one was with false-positive results. The sensitivity and positive predictive value of combined assessment of clinical examination and ultrasound scan on axillary node metastases were 92.1% and 93.3% in 81 patients. Those of combined assessment of clinical examination, ultrasound scan, and PET were 100% and 95.7% in 69 patients. FDG uptake in internal mammary node was seen in 14 out of 114 patients (12.2%). The positive predictive value of FDG-PET for detection of internal mammary metastases in 9 patients with pathologic confirmation was 75%. 6 of them were with true-positive, 2 were with false-positive, and 1 was false-negative. Among the 6 true positive patients, 3 were not detected internal mammary metastases in ultrasound scan. FDG uptake in the supraclavicular node was seen in 22 out of 114 patients (19.2%). The positive predictive value of FDG-PET for detection of supraclavicular metastases in 12 patients with pathologic confirmation was 58.3%. 7 of them were with true –positive and 5 were with false-positive. 1 of 7 true-positive patients was not detected supraclavicular lymph node metastases in ultrasound scan.&amp;#x2028; Conclusions: The sensitivity of FDG-PET for detection of axillary lymph node metastases was higher than that of FDG-PET for detection of internal mammary or supraclavicular lymph node. The addition of FDG-PET to standard work-up of locally advanced breast cancer patients could provide a more precise evaluation of regional lymph node metastases. Positive combined assessment of clinical examination, ultrasound scan and PET on axillary node metastases also could be an indication for full ALND without SNB. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4021.
AB0702 Entheses Scores in Clinical Practice – Correlation with Parameters of Disease Activity
Authors: J. Abelha-Aleixo, P. Madureira, R. Vieira, R. Fonseca, D. Gonçalves, M. Bernardes, A. Bernardo, L. Costa
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Enthesitis is a common and well described condition in spondylarthropathies. Currently several scores attempt to cover all affected areas in a practical way so that allows a reproducible assessment. <h3>Objectives</h3> To evaluate whether there is a correlation between the scores of entheses (SPARCC and MASES) and several clinical and laboratory parameters in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). <h3>Methods</h3> We made a retrospective analysis (July/2012 and December/2013) of all patients with AS and PsA under TNF antagonists treatment, using the national database for rheumatic patients. The demographic, clinic and laboratorial data, disease activity scores (ASDAS, BASDAI and DAS28-4V), quality and functional impairment parameters (HAQ, BASMI and BASFI), pain scales (EVAs) and entheses scores were collected. The Spearman correlation test was used (SPSS 21.0 for statistical data analysis). <h3>Results</h3> We analysed 114 patients with ankylosing spondylitis (65,8% men) with a median age of 45,0 years [19,1-79.9]; and 44 patients with psoriatic arthritis, (59,1% women) with a median age of 48,2 years [21,1-85,3]. The median disease duration was 21,6 years [2,5-49,5]) and 13,3 years [2,5-40,5], respectively. In the AS patients, moderate correlation (p&lt;0.05) was found between both SPARCC and MASES and: ASDAS (r=0,35: r=0,31), BASDAI (r=0,50; r=0,54), BASFI (r=0,30; r=0,33), global disease pain patient evaluation (r=0.34; r=0.33), global disease pain doctor evaluation (r=0,43; r=0,32), spine night pain evaluation (r=0,46; r=0,37), and spine global pain evaluation (r=0,38, r=0,39). In the PsA patients, moderate to strong correlations (p&lt;0.05) were found between both SPARCC and MASES and ASDAS (r=0,63; r=0,54), BASDAI (r=0,68; r=0,53), BASFI (r=0,52; r=0,41), DAS28 (4V) (r=0,72; r=0,47), HAQ (r=0,68; r=0,49) global disease pain patient evaluation (r=0.66; r=0.51), spine night pain evaluation (r=0,55; r=0,38), and spine global pain evaluation (r=0,54; r=0,38). Additionally SPARCC showed correlation with BASMI (r=0,39) and global disease pain doctor evaluation (r=0,59). No correlation was found between the scores of entheses and laboratory parameters (ESR and CRP), in both diseases. <h3>Conclusions</h3> This analysis suggests there is a correlation between the enthesis scores and the majority of the parameters evaluated, for AS and PSA patients. We may infer the usefulness of entheses scores as an evaluation tool, but more studies are needed to assess its prognostic power. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5711
A Comparison of the Side Effects and Antihypertensive Potency of Chlorothiazide and Hydrochlorothiazide
Authors: Richard E. Lee, Arthur W. Seligman, Melva A. Clark, Patricia A. Rousseau
Journal: New England Journal of Medicine (1960)

THE past decade has seen a dramatic change in the management of high blood pressure. A program consisting of sedatives, diets and surgery has gradually been replaced by one that is based on the use of antihypertensive medications, either singly or in various combinations. Although the great majority of subjects with hypertensive disease demonstrate a significant blood-pressure reduction and diminution or disappearance of certain symptoms when given these drugs1 2 3 many fail to respond satisfactorily. In such cases, when relatively small doses of the antihypertensive materials that were previously ineffective are supplemented with chlorothiazide, most "therapeutically refractory" cases can be managed . . .
PWE-127 Trends In Hospital Admissions With Alcohol Related Liver Disease In South-east England: Abstract PWE-127 Table 1
Authors: N Shah, BD Warner, J Potts, S Verma
Journal: Gut (2014)

<h3>Introduction</h3> Morbidity and mortality from alcohol related liver disease (ALD) has increased significantly in England. We aimed to assess the impact of the change in the alcohol licensing law in 2005 on hospital admission as well as morbidity and mortality from ALD. <h3>Methods</h3> This was a retrospective study between Jan 2006 to Dec 2011. Patients were identified using the ALD code (K70). Our institute is a teaching hospital in South-East England with a referral base of ~300,000 patients. Biochemical, radiological and microbiology data were collected for each patient from computerised records. The reason for hospital presentation, including the length-of-stay (and ITU stay) were collected. The data was analysed using the <i>t </i>test. <h3>Results</h3> During the study period there were a total of 294 admissions due to ALD. Amongst these, 33% presented to hospital with one admission and 67% had more than 1 admission. 69% were men (201/294), 31%(93/294) were women. The median age of the women and men in 2006 and 2007 was 56 and 52 years respectively. However, between 2008–2011, the median age of women presenting was 49 years. There was a rise in the number of admissions related to ALD each year: 40%(116/294) in 2006, 45%(133/294) in 2007, 59%(172/294) in 2008, 59%(171/294) in 2009, 66%(193/294) in 2010 and 68%(201/294) in 2011. Presentation with hyperbilirubinaemia was the most common cause of hospital admission at 72%(211/294), followed by gastrointestinal bleeding at 60%(179/294). Spontaneous bacterial peritonitis contributed to 22%(66/294) of admissions. 17%(51/294) had gram-negative and 6%(17/294) presented with gram-positive sepsis, whereas 15%(46/294) had infection of unknown origin. 28%(82/294) warranted ITU admission for organ support. The overall in-hospital mortality was 33%(96/294). The MELD in patients who died was 25 ± 0.9 vs 16.94 ± 0.2 in those that survived (p &lt; 0.0001) each year. The percentage of failing organs each year is shown in the table below. <h3>Conclusion</h3> A rise in the number of admissions and re-admissions with ALD in particular with acute on chronic liver failure is a major burden on health services. It is associated with high mortality and with multi-organ failure. Increasing awareness of alcohol as a health hazard needs to be a public health priority. Early recognition of acute on chronic liver failure and timely intervention to prevent its progression is required. <h3>Disclosure of Interest</h3> None Declared.
Abstract P2-12-07: A review of clinical endpoints and use of quality-of-life outcomes in phase III metastatic breast cancer clinical trials
Authors: R Tatla, D Landaverde, C Victor, D Miles, S Verma
Journal: Cancer Research (2012)

Abstract Background: The management of metastatic breast cancer (MBC) is often considered to be palliative, with most interventions intended to relieve disease symptoms, minimize treatment effects and prolong patient survival. The impact of disease and treatment on a patient's functional abilities has led to the emphasis of incorporating quality of life (QoL) measures into clinical trials. The primary objective of this study is to evaluate phase III clinical trials in MBC, and assess the inclusion of QoL as an endpoint, in addition to conventional progression and survival endpoints. Methods: A structured PubMed search was conducted to identify phase III clinical trials published between Jan. 1990 and Aug. 2011, which evaluated systemic treatment in MBC patients. Data pertaining to treatment regimens, study endpoints and clinical findings were collected, with a particular focus on progression-based (PB), overall survival (OS), and QoL endpoints. The instrument(s) used in evaluating QoL were also noted (when applicable). Results: Of 520 publications identified, 122 phase III MBC clinical trials met the inclusion criteria. Of these studies, 98.4% and 95.9% included PB and OS respectively, as clinical endpoints, while QoL was assessed in only 46 (37.7%) studies. 14 instruments were identified as QoL measurement tools among these studies, with EORTC QLQ-C30 and FACT-B accounting for 54.7% of the instruments used. While the inclusion of QoL was not associated with the significance of PB results, there was an association between the inclusion of QoL and OS results, with 59% of significant OS studies and 32% of non-significant OS studies including QoL as a clinical endpoint (p = 0.016). When stratified by treatment arm, it was found that studies favouring standard therapy were more likely to include QoL (75%, p = 0.045), compared to those favouring the intervention (56%), and those without significant differences (32%). Conclusions: Although the importance of QoL is often emphasized in MBC management and treatment decisions, only one-third of identified phase III clinical trials included an assessment of QoL. About half of these trials showed no statistically significant differences in QoL endpoint; of note, instruments of varying validity were utilized. There needs to be greater emphasis on the evaluation of QoL, with the use of standard and validated QoL tools in MBC clinical trials, especially as we increasingly focus on progression-based endpoints. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-07.
Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis
Authors: Ludwig Kappos, Heinz Wiendl, Krzysztof Selmaj, Douglas L. Arnold, Eva Havrdova, Alexey Boyko, Michael Kaufman, John Rose, Steven Greenberg, Marianne Sweetser, Katherine Riester, Gilmore O’Neill, Jacob Elkins
Journal: New England Journal of Medicine (2015)

Daclizumab high-yield process (HYP) is a humanized monoclonal antibody that binds to CD25 (alpha subunit of the interleukin-2 receptor) and modulates interleukin-2 signaling. Abnormalities in interleukin-2 signaling have been implicated in the pathogenesis of multiple sclerosis and other autoimmune disorders.