tbuckley/cabot-search huggingface dataset:
Combined Promoter Methylation Analysis of CADM1 and MAL: An Objective Triage Tool for High-Risk Human Papillomavirus DNA–Positive Women
Authors: Albertus T. Hesselink, Daniëlle AM Heideman, Renske DM Steenbergen, Veerle M.H. Coupé, Renee M. Overmeer, Dorien Rijkaart, Johannes Berkhof, Chris J.L.M. Meijer, Peter J.F. Snijders
Journal: Clinical Cancer Research (2011)

Screening women for high-grade cervical intraepithelial neoplasia or cervical cancer (CIN3(+)) by high-risk human papillomavirus (hrHPV) testing has as side-effect the detection of hrHPV-positive women without clinically relevant lesions. Here, we developed an objective assay assessing the methylation status of the promoter regions of CADM1 and MAL to triage hrHPV-positive women for CIN3(+).In a training set (51 women with CIN3(+) and 224 without CIN2(+)), panels consisting of one to four quantitative methylation-specific PCR (qMSP) assays (CADM1-m12,CADM1-m18,MAL-m1,MAL-m2) were analyzed. Cross-validated receiver-operating characteristics (ROC) curves were constructed and the panel with highest partial cross-validated area under the curve (AUC) was used for validation in an independent set of 236 consecutive hrHPV-positive women from a screening cohort. In the validation set, the ROC curve of the panel was compared with CIN3(+) sensitivity and specificity of cytology and of cytology combined with HPV16/18 genotyping.In the training set, CADM1-m18 combined with MAL-m1 was the best panel (cross-validated partial AUC = 0.719). In the validation set, this panel revealed CIN3(+) sensitivities ranging from 100% (95% CI: 92.4-100) to 60.5% (95% CI: 47.1-74.6), with corresponding specificities ranging from 22.7% (95% CI: 20.2-25.2) to 83.3% (95% CI: 78.4-87.4). For cytology these were 65.8% (95% CI: 52.3-79.0) and 78.8% (95% CI: 73.7-83.1) and for cytology/HPV16/18, these were 84.2% (95% CI: 72.0-92.7) and 54.0% (95% CI: 49.2-58.7), respectively. The point estimates of both cytology and cytology/HPV16/18 were equal to the values of the ROC curve of CADM1-m18/MAL-m1.We developed an objective methylation marker panel that was equally discriminatory for CIN3(+) as cytology or cytology with HPV16/18 genotyping in hrHPV-positive women. This opens the possibility for complete cervical screening by objective, nonmorphological molecular methods.
Patients with rheumatoid arthritis treated with tumour necrosis factor antagonists increase their participation in the workforce: potential for significant long-term indirect cost gains (data from a population-based registry)
Authors: J Augustsson, M Neovius, C Cullinane-Carli, S Eksborg, R F van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective:</h3> To investigate the effect of tumour necrosis factor (TNF) antagonist treatment on workforce participation in patients with rheumatoid arthritis (RA). <h3>Methods:</h3> Data from the Stockholm anti-TNFα follow-up registry (STURE) were used in this observational study. Patients with RA (n = 594) aged 18–55 years, (mean (SD) 40 (9) years) followed for up to 5 years were included with hours worked/week as the main outcome measure. Analyses were performed unadjusted and adjusted for baseline age, disease duration, Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28) and pain score. <h3>Results:</h3> At baseline patients worked a mean 20 h/week (SD 18). In unadjusted analyses, significant improvements in hours worked/week could already be observed in patients at 6 months (mean, 95% CI) +2.4 h (1.3 to 3.5), with further increases compared to baseline at 1-year (+4.0 h, 2.4 to 5.6) and 2-year follow-up (+6.3 h, 4.2 to 8.4). The trajectory appeared to stabilise at the 3-year (+6.3 h, 3.6 to 8.9), 4-year (+5.3 h, 2.3 to 8.4) and 5-year follow-up (+6.6 h, 3.3 to 10.0). In a mixed piecewise linear regression model, adjusted for age, sex, baseline disease activity, function and pain, an improvement of +4.2 h/week was estimated for the first year followed by an added improvement of +0.5 h/week annually during the years thereafter. Over 5 years of treatment, the expected indirect cost gain corresponded to 40% of the annual anti-TNF drug cost in patients continuing treatment. <h3>Conclusion:</h3> Data from this population-based registry indicate that biological therapy is associated with increases in workforce participation in a group typically expected to experience progressively deteriorating ability to work. This could result in significant indirect cost benefits to society.
Non-endoscopic immunocytological screening test for Barrett's oesophagus
Authors: P. Lao-Sirieix, B. Rous, M. O'Donovan, R. H Hardwick, I. Debiram, R. C Fitzgerald
Journal: Gut (2007)

Epidemiology of microscopic colitisWe read the interesting paper by Pardi et al on the epidemiology of microscopic colitis in Olmsted County, Minnesota, USA (Gut 2007; 56: 504-8).They concluded that the incidence of microscopic colitis increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously.In fact, compared with other epidemiological studies, in the last years of the study period they describe the highest incidence figures of microscopic colitis ever reported.However, is difficult to compare the crude incidence rates of several studies if we do not know the age structure of the population pyramid of each geographical area.As microscopic colitis is associated with older age, a higher incidence will be expected among aging populations.A solution for this is to report the standardised incidence rates; however, they are not reported in most of the published epidemiological studies.Another possibility is to describe the population pyramid of each geographical area.We think that the paper of Pardi et al would have been more understandable if they had described the population pyramid of Olmsted County.In our epidemiological study on the incidence of microscopic colitis in Terrassa, Spain, 1 we reported the population pyramid.Thus, Pardi et al should assess if there are any differences in the age structure and sex structure of the population pyramids between Olmsted County and Terrassa.In this sense, if population pyramids were similar, they could conclude that there is a true difference in the incidence of microscopic colitis.
Hospital admissions for peptic ulcer and indigestion in London and New York in the 19th and early 20th centuries
Authors: J H Baron
Journal: Gut (2002)

The occurrence of peptic ulcer increased rapidly in all Western countries from the 19th to the 20th century, attributed to a possible epidemic of <i>Helicobacter pylori</i>, a new pathogenic strain, or a change in host susceptibility. The early trends in hospital admissions for peptic ulcer and dyspepsia in London and New York during the 19th century are reviewed to test these hypotheses.
Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?
Authors: J. Mezynski, C. Pezaro, D. Bianchini, A. Zivi, S. Sandhu, E. Thompson, J. Hunt, E. Sheridan, B. Baikady, A. Sarvadikar, G. Maier, A.H.M. Reid, A. Mulick Cassidy, D. Olmos, G. Attard, J. de Bono
Journal: Annals of Oncology (2012)
US Medical School Finances
Authors: Leanne D. Jolin
Journal: JAMA (1992)

THIS 32nd review of medical school finances reports revenue and expenditures for all 126 fully accredited US medical schools for fiscal year 1990-1991 and identifies trends in the financing of medical education. The data also reflect changes across a 30-year period in the number of faculty, house staff, and medical students. <h3>DATA SOURCES AND CHARACTERISTICS</h3> Data were derived from medical schools' responses to the annual questionnaire of the Liaison Committee on Medical Education (LCME). For financial reporting, the LCME defines a medical school in terms of its faculty activities, including research and patient care as well as instruction. All revenues and expenditures that support the school's full-time faculty and their activities are included, whether or not these are recorded in medical school accounts. This definition makes the finances of medical schools with different organizational forms more nearly comparable. Many other organizational entities provide financial support for medical school activities. The
Inducible re-expression of HEXIM1 causes physiological cardiac hypertrophy in the adult mouse
Authors: Monica M. Montano, Candida L. Desjardins, Yong Qui Doughman, Yee-Hsee Hsieh, Yanduan Hu, Heather M. Bensinger, Connie Wang, Julian E. Stelzer, Thomas E. Dick, Brian D. Hoit, Margaret P. Chandler, Xin Yu, Michiko Watanabe
Journal: Cardiovascular Research (2013)

AimsThe transcription factor hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1) regulates myocardial vascularization and growth during cardiogenesis. Our aim was to determine whether HEXIM1 also has a beneficial role in modulating vascularization, myocardial growth, and function within the adult heart.
Differential G protein subunit expression by prostate cancer cells and their interaction with CXCR5
Authors: Christelle P El-Haibi, Praveen Sharma, Rajesh Singh, Pranav Gupta, Dennis D Taub, Shailesh Singh, James W Lillard, Jr
Journal: Molecular Cancer (2013)

Abstract Background Prostate cancer (PCa) cell lines and tissues differentially express CXCR5, which positively correlate with PCa progression, and mediate PCa cell migration and invasion following interaction with CXCL13. However, the differential expression of G protein α, β, and γ subunits by PCa cell lines and the precise combination of these proteins with CXCR5 has not been elucidated. Methods We examined differences in G protein expression of normal prostate (RWPE-1) and PCa cell lines (LNCaP, C4-2B, and PC3) by western blot analysis. Further, we immunoprecipitated CXCR5 with different G protein subunits, and CXCR4, following CXCL13 stimulation. To investigate constitutive coupling of CXCR5 with CXCR4 and PAR-1 we performed invasion assay in PCa cells transfected with G αq/i2 or G α13 siRNA, following CXCL13 treatment. We also investigated Rac and RhoA activity by G-LISA activation assay in PCa cells following CXCL13/thrombin stimulation. Result Of the 22 G proteins studied, G αi1-3 , G β1-4 , G γ5 , G γ7 , and G γ10 were expressed by both normal and PCa cell lines. G αs was moderately expressed in C4-2B and PC3 cell lines, G αq/11 was only present in RWPE-1 and LNCaP cell lines, while G α12 and G α13 were expressed in C4-2B and PC3 cell lines. G γ9 was expressed only in PCa cell lines. G α16 , G β5 , G γ1-4 , and G γ13 were not detected in any of the cell lines studied. Surprisingly, CXCR4 co-immunoprecipitated with CXCR5 in PCa cell lines irrespective of CXCL13 treatment. We also identified specific G protein isoforms coupled to CXCR5 in its resting and active states. G αq/11/ G β3/ G γ9 in LNCaP and G αi2/ G β3/ G γ9 in C4-2B and PC3 cell lines, were coupled to CXCR5 and disassociated following CXCL13 stimulation. Interestingly, G α13 co-immunoprecipitated with CXCR5 in CXCL13-treated, but not in untreated PCa cell lines. Inhibition of G αq/i2 significantly decreased the ability of cells to invade, whereas silencing G α13 did not affect CXCL13-dependent cell invasion. Finally, CXCL13 treatment significantly increased Rac activity in G αq/i2 dependent manner, but not RhoA activity, in PCa cell lines. Conclusions These findings offer insight into molecular mechanisms of PCa progression and can help to design some therapeutic strategies involving CXCR5 and/or CXCL13 blockade and specific G protein inhibition to abrogate PCa metastasis.
c-Met Ectodomain Shedding Rate Correlates with Malignant Potential
Authors: Gagani Athauda, Alessio Giubellino, Jonathan A. Coleman, Christine Horak, Patricia S. Steeg, Ming-Jung Lee, Jane Trepel, Jennifer Wimberly, Jan Sun, Angela Coxon, Teresa L. Burgess, Donald P. Bottaro
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Many proteins are proteolytically released from the cell surface by a process known as ectodomain shedding. Shedding occurs under normal physiologic conditions and can be increased in certain pathologies. Among the many receptors for which ectodomain shedding has been shown is c-Met, the hepatocyte growth factor (HGF) receptor tyrosine kinase. HGF stimulates mitogenesis, motogenesis, and morphogenesis in a variety of cellular targets during development, homeostasis, and tissue regeneration. Inappropriate HGF signaling resulting in unregulated cell proliferation, motility, and invasion occurs in several human malignancies. This can occur through paracrine signaling, autocrine loop formation, receptor mutation, gene amplification, or gene rearrangement, accompanied frequently with overexpression of ligand and/or receptor proteins. We hypothesized that c-Met overexpression in cancer might result in increased ectodomain shedding, and that its measure could be a useful biomarker of tumor progression. Experimental Design: We developed a sensitive electrochemiluminescent immunoassay to quantitate c-Met protein in cell lysates, culture supernatants, and biological samples. Results: A survey of cultured cell models of oncogenic transformation revealed significant direct correlations (P &amp;lt; 0.001, t test or ANOVA) between malignant potential and the rate of c-Met ectodomain shedding that was independent of steady-state receptor expression level. Moreover, weekly plasma and urine samples from mice harboring s.c. human tumor xenografts (n = 4 per group) displayed soluble human c-Met levels that were measurable before tumors became palpable and that correlated directly with tumor volume (R2 &amp;gt; 0.92, linear regression). Conclusions: For a variety of human cancers, c-Met ectodomain shedding may provide a reliable and practical indicator of malignant potential and overall tumor burden.
THE NORMAL FLORA OF THE SKIN IN DIFFERENT AGE GROUPS
Authors: DOROTHY A. SOMERVILLE
Journal: British Journal of Dermatology (1969)

SUMMARY. An investigation of the incidence and distribution of aerobic organisms included in the cutaneous community in 410 persons is described. These subjects were divided by age into 4 groups: infants, children, adults and geriatrics. The age of the individual was found to influence the bacterial flora found on the skin. Coagulase negative staphylococci and micrococci occurred frequently in virtually all sites in each person sampled. Other major Inhabitants of the skin were, in the infants, streptococci, in the adults, diphtheroids and in the old people, diphtheroids and streptococci. The flora was very varied in the children with Sarcina, diphtheroids, spore forming bacilli and Gram‐negative bacilli frequently found in large numbers.
EEG Abnormalities During Treatment With Typical and Atypical Antipsychotics
Authors: Franca Centorrino, Bruce H Price, Margaret Tuttle, Won-Myong Bahk, John Hennen, Matthew J Albert, Ross J Baldessarini
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Clozapine produces EEG abnormalities and dose-dependent risk of epileptic seizures. Much less is known about EEG effects of newer antipsychotics. The present study therefore examined the risk of EEG abnormalities associated with various antipsychotic drugs. METHOD: EEG recordings from 323 hospitalized psychiatric patients (293 treated with antipsychotics, 30 who did not receive any antipsychotic treatment) were graded blind to diagnosis and treatment for type and severity of EEG abnormalities. Drug type, dose, and clinical factors were evaluated for association with EEG abnormalities by multivariate logistic regression. RESULTS: EEG abnormalities occurred in 56 subjects (19.1%) treated and four (13.3%) not treated with antipsychotics. EEG abnormality risk among antipsychotic agents varied greatly (clozapine=47.1%, olanzapine=38.5%, risperidone=28.0%, typical neuroleptics=14.5%, quetiapine=0.0%). Significant risk factors in order of influence were hypertension, use of an atypical antipsychotic, bipolar diagnosis, and older age; benzodiazepine cotreatment lowered risk. Unassociated with risk were sex, treatment response, length of hospital stay, drug potency, daily dose (in mg or mg/kg), drug exposure time, or cotreatments. CONCLUSIONS: EEG abnormality risk varied widely among specific antipsychotics. Risk was particularly high with clozapine and olanzapine, moderate with risperidone and typical neuroleptics, and low with quetiapine. Comorbid hypertension, bipolarity, and older age—but not dose or clinical response—were associated with risk.
Renal Function in Mice with Targeted Disruption of the A Isoform of the Na-K-2Cl Co-Transporter
Authors: Mona Oppermann, Diane Mizel, Soo Mi Kim, Limeng Chen, Robert Faulhaber-Walter, Yuning Huang, Cuiling Li, Chuxia Deng, Josie Briggs, Jurgen Schnermann, Hayo Castrop
Journal: Journal of the American Society of Nephrology (2007)

Three different full-length splice isoforms of the Na-K-2Cl co-transporter (NKCC2/BSC1) are expressed along the thick ascending limb of Henle (TAL), designated NKCC2A, NKCC2B, and NKCC2F. NKCC2F is expressed in the medullary, NKCC2B mainly in the cortical, and NKCC2A in medullary and cortical portions of the TAL. NKCC2B and NKCC2A were shown to be coexpressed in the macula densa (MD) segment of the mouse TAL. The functional consequences of the existence of three different isoforms of NKCC2 are unclear. For studying the specific role of NKCC2A in kidney function, NKCC2A-/- mice were generated by homologous recombination. NKCC2A-/- mice were viable and showed no gross abnormalities. Ambient urine osmolarity was reduced significantly in NKCC2A-/- compared with wild-type mice, but water deprivation elevated urine osmolarity to similar levels in both genotypes. Baseline plasma renin concentration and the effects of a high- and a low-salt diet on plasma renin concentration were similar in NKCC2A+/+ and -/- mice. However, suppression of renin secretion by acute intravenous saline loading (5% of body weight), a measure of MD-dependent inhibition of renin secretion, was reduced markedly in NKCC2A-/- mice compared with wild-type mice. Cl and water absorption along microperfused loops of Henle of NKCC2A-/- mice were unchanged at normal flow rates but significantly reduced at supranormal flow. Tubuloglomerular feedback function curve as determined by stop flow pressure measurements was left-shifted in NKCC2A-/- compared with wild-type mice, with maximum responses being significantly diminished. In summary, NKCC2A activity seems to be required for MD salt sensing in the high Cl concentration range. Coexpression of both high- and low-affinity isoforms of NKCC2 may permit transport and Cl-dependent tubuloglomerular feedback regulation to occur over a wider Cl concentration range.
Comparison between the bacterial and oligosaccharide content of ileostomy effluent in subjects taking diets rich in refined or unrefined carbohydrate.
Authors: L Berghouse, S Hori, M Hill, M Hudson, J E Lennard-Jones, E Rogers
Journal: Gut (1984)

Dietary surveys have shown that patients with Crohn9s disease tend to eat more sucrose than control subjects and this investigation was undertaken to determine whether a diet rich in refined carbohydrate affects the bacterial flora of the terminal ileum. Ileostomy effluent in five patients with Crohn9s disease and five with ulcerative colitis after two weeks on a diet rich in sucrose and refined cereal has been compared with the same period on a diet low in sucrose and rich in unrefined cereal. Observations were made hourly for nine hours after equicaloric breakfasts representing the two diets. The amount of ileostomy effluent was greater on the unrefined carbohydrate diet both in terms of wet weight (238 +/- 89 g vs 162 +/- 79 g, p less than 0.02) and dry weight (23 X 6 +/- 6.8 g vs 14.9 +/- 6.6 g, p less than 0.01); surprisingly, the amount of glucose and oligosaccharide was also greater (169 +/- 41 mg vs 82 +/- 26 mg, p less than 0.001) in all 10 volunteers. The bacteriological flora per gram was also higher on the unrefined carbohydrate diet after the test meal (p less than 0.02 between three and six hours) as a result of a general increase in all organisms. The relative proportions of the organisms did not vary between the two diets. No differences were detected between patients with ulcerative colitis and those with Crohn9s disease.
Evolutionary Meta-Analysis of Association Studies Reveals Ancient Constraints Affecting Disease Marker Discovery
Authors: J. T. Dudley, R. Chen, M. Sanderford, A. J. Butte, S. Kumar
Journal: Molecular Biology and Evolution (2012)

Genome-wide disease association studies contrast genetic variation between disease cohorts and healthy populations to discover single nucleotide polymorphisms (SNPs) and other genetic markers revealing underlying genetic architectures of human diseases. Despite scores of efforts over the past decade, many reproducible genetic variants that explain substantial proportions of the heritable risk of common human diseases remain undiscovered. We have conducted a multispecies genomic analysis of 5,831 putative human risk variants for more than 230 disease phenotypes reported in 2,021 studies. We find that the current approaches show a propensity for discovering disease-associated SNPs (dSNPs) at conserved genomic positions because the effect size (odds ratio) and allelic P value of genetic association of an SNP relates strongly to the evolutionary conservation of their genomic position. We propose a new measure for ranking SNPs that integrates evolutionary conservation scores and the P value (E-rank). Using published data from a large case-control study, we demonstrate that E-rank method prioritizes SNPs with a greater likelihood of bona fide and reproducible genetic disease associations, many of which may explain greater proportions of genetic variance. Therefore, long-term evolutionary histories of genomic positions offer key practical utility in reassessing data from existing disease association studies, and in the design and analysis of future studies aimed at revealing the genetic basis of common human diseases.
Vaccine-Instructed Intratumoral IFN-γ Enables Regression of Autochthonous Mouse Prostate Cancer in Allogeneic T-Cell Transplantation
Authors: Rodrigo Hess Michelini, Teresa Manzo, Tabea Sturmheit, Veronica Basso, Martina Rocchi, Massimo Freschi, Joanna Listopad, Thomas Blankenstein, Matteo Bellone, Anna Mondino
Journal: Cancer Research (2013)

Abstract Vaccination can synergize with transplantation of allogeneic hematopoietic stem cells to cure hematologic malignancies, but the basis for this synergy is not understood to the degree where such approaches could be effective for treating solid tumors. We investigated this issue in a transgenic mouse model of prostate cancer treated by transplantation of a nonmyeloablative MHC-matched, single Y chromosome–encoded, or multiple minor histocompatibility antigen-mismatched hematopoietic cell preparation. Here, we report that tumor-directed vaccination after allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion is essential for acute graft versus tumor responses, tumor regression, and prolonged survival. Vaccination proved essential for generation of CD8+ IFN-γ+ tumor-directed effector cells in secondary lymphoid organs and also for IFN-γ+ upregulation at the tumor site, which in turn instructed local expression of proinflammatory chemokines and intratumoral recruitment of donor-derived T cells for disease regression. Omitting vaccination, transplanting IFN-γ–deficient donor T cells, or depleting alloreactive T cells all compromised intratumoral IFN-γ–driven inflammation and lymphocyte infiltration, abolishing antitumor responses and therapeutic efficacy of the combined approach. Our findings argue that posttransplant tumor-directed vaccination is critical to effectively direct donor T cells to the tumor site in cooperation with allogeneic hematopoietic cell transplantation. Cancer Res; 73(00); 4641–52. ©2013 AACR.