tbuckley/cabot-search huggingface dataset:
Guideline-discordant androgen deprivation therapy in localized prostate cancer: patterns of use in the medicare population and cost implications
Authors: A.R. Kuykendal, L.H. Hendrix, R.G. Salloum, P.A. Godley, R.C. Chen
Journal: Annals of Oncology (2013)

BackgroundAndrogen deprivation therapy (ADT) in localized prostate cancer improves overall survival and is recommended by National Comprehensive Cancer Network guidelines in certain situations. However, ADT is without benefit in other situations and can actually cause harm. This study examines recent trends in the ADT use and quantifies the cost of guideline-discordant ADT.Patients and methodsPatients, aged 66–80 years, in the Surveillance Epidemiology and End Results-Medicare database with non-metastatic prostate cancer diagnosed between 2004 and 2007 were included for analysis. Prostate-specific antigen, Gleason score, and stage were used to define D'Amico risk categories. Logistic regression was used to examine factors associated with guideline-discordant ADT. Annual direct cost was estimated using 2011 Medicare reimbursement for ADT.ResultsOf 28 654 men included, 12.4% received guideline-discordant ADT. In low-risk patients, 14.9% received discordant ADT, mostly due to simultaneous ADT with radiation. Discordant use was seen in 7.3% of intermediate and 14.9% of high-risk patients, mostly from ADT as primary therapy. The odds of receiving guideline-discordant ADT decreased over time (2007 versus 2004; OR 0.69; 95% CI 0.62–0.76). The estimated annual direct cost from discordant ADT is $42 000 000.ConclusionApproximately one in eight patients received ADT discordant with published guidelines. Elimination of discordant use would result in substantial savings.
Gossip as an effective and low-cost form of punishment
Authors: Matthew Feinberg, Joey T. Cheng, Robb Willer
Journal: Behavioral and Brain Sciences (2012)

Abstract The spreading of reputational information about group members through gossip represents a widespread, efficient, and low-cost form of punishment. Research shows that negative arousal states motivate individuals to gossip about the transgressions of group members. By sharing information in this way groups are better able to promote cooperation and maintain social control and order.
GC Composition of the Human Genome: In Search of Isochores
Authors: Netta Cohen, Tal Dagan, Lewi Stone, Dan Graur
Journal: Molecular Biology and Evolution (2005)

The isochore theory, proposed nearly three decades ago, depicts the mammalian genome as a mosaic of long, fairly homogeneous genomic regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five distinct isochore families: L1, L2, H1, H2, and H3, with GC contents of <37%, 37%–42%, 42%–47%, 47%–52%, and >52%, respectively. In this paper, we address the question of the validity of the isochore theory through a rigorous sequence-based analysis of the human genome. Toward this end, we adopt a set of six attributes that are generally claimed to characterize isochores and statistically test their veracity against the available draft sequence of the complete human genome. By the selection criteria used in this study: distinctiveness, homogeneity, and minimal length of 300 kb, we identify 1,857 genomic segments that warrant the label "isochore." These putative isochores are nonuniformly scattered throughout the genome and cover about 41% of the human genome. We found that a four-family model of putative isochores is the most parsimonious multi-Gaussian model that can be fitted to the empirical data. These families, however, are GC poor, with mean GC contents of 35%, 38%, 41%, and 48% and do not resemble the five isochore families in the literature. Moreover, due to large overlaps among the families, it is impossible to classify genomic segments into isochore families reliably, according to compositional properties alone. These findings undermine the utility of the isochore theory and seem to indicate that the theory may have reached the limits of its usefulness as a description of genomic compositional structures.
Immunoregulation in onchocerciasis. Functional and phenotypic abnormalities of lymphocyte subsets and changes with therapy.
Authors: D O Freedman, A Lujan-Trangay, C Steel, C Gonzalez-Peralta, T B Nutman
Journal: Journal of Clinical Investigation (1991)

To help define the immunoregulatory defects in patients with onchocerciasis, flow cytometric analysis of circulating lymphocyte subpopulations was performed in parallel with functional assays. No significant differences in CD4/CD8 ratios were seen when microfilariae-positive individuals from Guatemala were compared with Guatemalan controls. However, the infected individuals had significantly increased numbers of circulating CD4+CD45RA+ lymphocytes (mean 38.3%) when compared with controls (mean 16.0%). Coexpression of the activation marker HLA-DR was significantly increased on CD4+ cells from infected individuals. In contrast, no up-regulation of HLA-DR was seen on CD8+ or CD19+ cells. At 1 year after initiation of treatment with semiannual doses of the microfilaricide ivermectin, there were significant increases (P less than 0.05) in the percentage of CD4+CD45RA- cells, the percentage of CD4+HLA-DR+ cells, and mitogen-induced lymphokine production (IL-2, IL-4). Despite these changes, parasite-specific IL-2 and IL-4 production which had been undetectable before treatment did not manifest itself even by the 2-yr follow-up. Defects in the T-cell activation pathway in Onchocerca volvulus-infected individuals may thus exist at several independent points; a state of parasite antigen-specific tolerance appears to remain even after the relative reversal of other generalized immunoregulatory defects.
Respiratory Changes After Open-heart Surgery
Authors: J. B. McClenahan, W. E. Young, M. K. Sykes
Journal: Thorax (1965)

1-0 to 1-5 mg./kg., one hour before operation.Anaes- thesia was induced with thiopentone, 50 to 250 mg., and muscular relaxation was obtained with D-tubocurarine, 15 to 30 mg.Respirations were controlled using a mixture of nitrous oxide 70% and oxygen 30% from a non- rebreathing system on a mechanical ventilator, except during the period of total cardiopulmonary bypass, when the lungs were held inflated with a mixture of helium, or nitrogen, and oxygen.Small doses of pethidine, 10 to 545 on July 17,
Genetic alterations in pancreatic carcinoma.
Authors: Gunter Schneider, Roland M Schmid
Journal: Molecular Cancer (2003)

Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%. Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques. Pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. In this article we describe major genetic alterations of pancreatic cancer, mutations in the proto-oncogene K-RAS and the tumor suppressors INK4A, TP53 and DPC4/SMAD4. The accumulation of these genetic changes leads to a profound disturbance in cell cycle regulation and continuous growth. The knowledge of the underlying molecular mechanisms will offer new therapeutic and diagnostic options and hopefully improve the outcome of this aggressive disease.
Active8: a randomized, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with TLR8 agonist VTX-2337 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)
Authors: Robert L Ferris, Ezra Cohen, Kelly Gash, Sam Whiting, Kristi Manjarrez, Greg Dietsch, Robert Hershberg, James Bryan
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Recurrent or metastatic SCCHN has few effective therapeutic options. In these patients, the EXTREME regimen added Cetuximab--an EGFR-specific monoclonal antibody--to a regimen of Platinum/5-FU and improved median overall survival (OS) by 2.7 months and progression-free survival (
Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response
Authors: Philipp Enghard, Claudia Rieder, Katharina Kopetschke, J R Klocke, Reinmar Undeutsch, Robert Biesen, Duska Dragun, Maik Gollasch, Udo Schneider, Karlfried Aupperle, Jens Y Humrich, Falk Hiepe, Marina Backhaus, A H Radbruch, Gerd R Burmester, Gabriela Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Proliferative lupus nephritis (LN) is one of the major concerns in the treatment of systemic lupus erythematosus (SLE). Here we evaluate urinary CD4 T cells as a biomarker of active LN and indicator of treatment response. <h3>Methods</h3> Urinary CD3CD4 T cells were quantified using flow cytometry in 186 urine samples from 147 patients with SLE. Fourteen patients were monitored as follow-up. Thirty-one patients with other nephropathies and 20 healthy volunteers were included as controls. <h3>Results</h3> In SLE, urinary CD4 T cell counts ≥800/100 ml were observed exclusively in patients with active LN. Receiver operator characteristic analysis documented clear separation of SLE patients with active and non-active LN (area under the curve 0.9969). All patients with up-to-date kidney biopsy results showing proliferative LN had high urinary CD4 T cell numbers. In patients monitored under therapy, normalisation of urinary CD4 T cell counts indicated lower disease activity and better renal function. In contrast, patients with persistence of, or increase in, urinary T cells displayed worse outcomes. <h3>Conclusions</h3> Urinary CD4 T cells are a highly sensitive and specific marker for detecting proliferative LN in patients with SLE. Furthermore, monitoring urinary CD4 T cells may help to identify treatment responders and treatment failure and enable patient-tailored therapy in the future.
Crizotinib in<i>ALK</i>-Rearranged Inflammatory Myofibroblastic Tumor
Authors: James E. Butrynski, David R. D'Adamo, Jason L. Hornick, Paola Dal Cin, Cristina R. Antonescu, Suresh C. Jhanwar, Marc Ladanyi, Marzia Capelletti, Scott J. Rodig, Nikhil Ramaiya, Eunice L. Kwak, Jeffrey W. Clark, Keith D. Wilner, James G. Christensen, Pasi A. Jänne, Robert G. Maki, George D. Demetri, Geoffrey I. Shapiro
Journal: New England Journal of Medicine (2010)

Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation. These results support the dependence of ALK-rearranged tumors on ALK-mediated signaling and suggest a therapeutic strategy for genomically identified patients with the aggressive form of this soft-tissue tumor. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.).
Prediction of proximal advanced neoplasia: a comparison of four existing sigmoidoscopy-based strategies in a Chinese population
Authors: Martin C S Wong, Jessica Y L Ching, Siew C Ng, Sunny Wong, Victor C W Chan, Jeffrey P Shum, Thomas Y T Lam, Arthur K C Luk, Joseph J Y Sung
Journal: Gut (2014)

<h3>Objective</h3> To compare the performance of existing sigmoidoscopy-based strategies in predicting advanced proximal neoplasia (APN) in an asymptomatic Chinese cohort. <h3>Design</h3> We included all screening participants aged 50–70 years who received colonoscopy between 2008 and 2014 in Hong Kong. Sigmoidoscopy yield was estimated from the colonoscopic findings based on the: (1) UK flexible sigmoidoscopy; (2) Screening for COlon REctum (SCORE); (3) NORwegian Colorectal Cancer Prevention (NORCCAP) trials and (4) US clinical index based on age, gender and distal findings. The sensitivity, specificity, the number of subjects needed to screen (NNS) and the number of subjects needed to refer (NNR) for colonoscopy to detect one APN were evaluated. Binary logistic regression modelling identified the distal findings associated with APN. <h3>Results</h3> From 5879 eligible subjects, 132 (2.2%) had APN. The US strategy achieved the highest sensitivity for APN detection (42.0%) and the UK criteria attained the highest specificity (96%). The US criteria led to the lowest NNS (92 vs 103–267) and the UK criteria required the least NNR (12 vs 16–21). Using the US strategy, the rates of APN detected were 1.4% (low-risk group), 2.2% (intermediate risk) and 5.9% (high risk). The c-statistics of the UK, SCORE, NORCCAP and the US criteria were 0.55±0.03; 0.59±0.03; 0.59±0.03 and 0.62±0.05 respectively. <h3>Conclusions</h3> The US criteria had the highest sensitivity for detection of APN and lowest NNS and the UK score had the highest specificity and the lowest NNR. The performance of all these four criteria to predict APN is limited, highlighting an urgent need to devise a novel APN prediction system for Asian subjects.
Population and age-group trends in weekend sun protection and sunburn over two decades of the SunSmart programme in Melbourne, Australia
Authors: J.K. Makin, C.D. Warne, S.J. Dobbinson, M.A. Wakefield, D.J. Hill
Journal: British Journal of Dermatology (2012)

In response to the high skin cancer burden in Australia, the multicomponent, community-wide SunSmart programme has worked since 1988 to reduce excessive sun exposure. To examine trends in key sun-protection behaviours and sunburn for the Melbourne population from 1987 to 2007, and examine for the first time patterns of change among age groups. Representative cross-sectional weekly telephone surveys of weekend sun protection and sunburn were conducted over 11 of the summers in the period 1987-88 to 2006-07. Trends were analysed for the population and for age groups, adjusting for ambient temperature and ultraviolet radiation, which are environmental determinants of sun-related behaviour and sunburn. The general pattern of trends suggests two distinct periods, one with rapid improvement in behaviours (more sunscreen use, less unprotected body exposure and less sunburn) from 1987-88 to 1994-95, and the second from 1997-98 to 2006-07 with fewer changes in behaviours noted. The age-group analyses showed a similar pattern of change over time across groups, with a few notable exceptions. The similarity of the pattern of trends among age groups suggests that external influences including the SunSmart programme's activity had a relatively similar impact across the population. Sun-related behaviours continue to be amenable to change. More recent relative stability with some declines in sun protection suggests further intensive campaigns and other strategies may be needed to maintain previous successes and to achieve more universal use of sun protection.
Targeting a Glioblastoma Cancer Stem-Cell Population Defined by EGF Receptor Variant III
Authors: David R. Emlet, Puja Gupta, Marina Holgado-Madruga, Catherine A. Del Vecchio, Siddhartha S. Mitra, Shuang-Yin Han, Gordon Li, Kristin C. Jensen, Hannes Vogel, Linda Wei Xu, Stephen S. Skirboll, Albert J. Wong
Journal: Cancer Research (2013)

The relationship between mutated proteins and the cancer stem-cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGF receptor (EGFR) variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here, we show that EGFRvIII is highly coexpressed with CD133 and that EGFRvIII(+)/CD133(+) defines the population of cancer stem cells (CSC) with the highest degree of self-renewal and tumor-initiating ability. EGFRvIII(+) cells are associated with other stem/progenitor markers, whereas markers of differentiation are found in EGFRvIII(-) cells. EGFRvIII expression is lost in standard cell culture, but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII(+)/CD133(+) coexpression, self-renewal, and tumor initiating abilities. Elimination of the EGFRvIII(+)/CD133(+) population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC-specific expression and be used to specifically target this population.
Acquisition of High-Level Chromosomal Instability Is Associated with Integration of Human Papillomavirus Type 16 in Cervical Keratinocytes
Authors: Mark R. Pett, William O. F. Alazawi, Ian Roberts, Sally Dowen, David I. Smith, Margaret A. Stanley, Nicholas Coleman
Journal: Cancer Research (2004)

Abstract Whereas two key steps in cervical carcinogenesis are integration of high-risk human papillomavirus (HR-HPV) and acquisition of an unstable host genome, the temporal association between these events is poorly understood. Chromosomal instability is induced when HR-HPV E7 oncoprotein is overexpressed from heterologous promoters in vitro. However, it is not known whether such events occur at the “physiologically” elevated levels of E7 produced by deregulation of the homologous HR-HPV promoter after integration. Indeed, an alternative possibility is that integration in vivo is favored in an already unstable host genome. We have addressed these issues using the unique human papillomavirus (HPV) 16-containing cervical keratinocyte cell line W12, which was derived from a low-grade squamous intraepithelial lesion and thus acquired HPV16 by “natural” infection. Whereas W12 at low passage contains HPV16 episomes only, long-term culture results in the emergence of cells containing integrated HPV16 only. We show that integration of HPV16 in W12 is associated with 3′ deletion of the E2 transcriptional repressor, resulting in deregulation of the homologous promoter of the integrant and an increase in E7 protein levels. We further demonstrate that high-level chromosomal instability develops in W12 only after integration and that the forms of instability observed correlate with the physical state of HPV16 DNA and the level of E7 protein. Whereas intermediate E7 levels are associated with numerical chromosomal abnormalities, maximal levels are associated with both numerical and structural aberrations. HR-HPV integration is likely to be a critical event in cervical carcinogenesis, preceding the development of chromosomal abnormalities that drive malignant progression.
Inactıve hepatitis B surface antigen carriers and intrafamilial tramsmission: results of a 10-year study
Authors: Nese Demirturk, Tuna Demirdal
Journal: Clinical and Molecular Hepatology (2014)

The aims of the present study were to determine the outcomes of inactive hepatitis B virus (HBV) surface antigen (HBsAg) carriers over a 10-year study period and to elucidate the HBV serological profile of their family members.We retrospectively analyzed the medical files of inactive HBsAg carriers followed up at the Department of Infectious Diseases of Kocatepe University Medical Faculty Hospital between March 2001 and January 2011.In total, 438 inactive HBsAg carriers were enrolled in this trial. The follow-up period was 33.7 ± 22.5 months (mean ± SD). Anti-hepatitis-B surface antibody seroconversion occurred in 0.7% of cases, while chronic hepatitis B was found in 0.5%. The anti-hepatitis-D virus (HDV) status was evaluated in 400 patients and anti-hepatitis C virus (HCV) in 430. It was found that 1% and 0.2% were positive for anti-HDV and anti-HCV, respectively. HBV serology was investigated in at least 1 family member of 334/438 (76.3%) patients. The HBsAg positivity rate was 34.6% in 625 family members of 334 patients. A comparison of the HBsAg positivity rates in terms of HBV DNA levels in index cases revealed that HBsAg seropositivity rates were higher in family members of HBV DNA-negative patients than in family members of HBV DNA-positive cases (P=0.0001).The HBsAg positivity rate was higher in family members of inactive HBsAg carriers than in the general population; these family members therefore have a higher risk of HBV transmission. Furthermore, despite negative HBV DNA levels, transmission risk was not reduced in these patients, and horizontal transmission seems to be independent of the HBV DNA value.
Preclinical Evaluation of Antiangiogenic Thrombospondin-1 Peptide Mimetics, ABT-526 and ABT-510, in Companion Dogs with Naturally Occurring Cancers
Authors: Anthony Rusk, Evelyn McKeegan, Fortuna Haviv, Sandra Majest, Jack Henkin, Chand Khanna
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The angiogenic phenotype of malignant cancers has been established as a target for cancer therapy. ABT-526 and ABT-510, two peptide mimetics of thrombospondin-1 (TSP-1), block angiogenesis in vitro and in vivo and slow tumor growth in mice. To guide the clinical development of these drugs, translational studies in dogs with naturally occurring cancers were initiated. Experimental Design: A prospective open-label trial using ABT-510 or ABT-526 in pet dogs with measurable malignant spontaneously arising tumors. Endpoints included safety, pharmacokinetics, antitumor activity, and preliminary assessment of changes in circulating endothelial cell populations. Results: Two-hundred and forty-two dogs were sequentially entered to this open-label trial. The elimination half-life for ABT-510 and ABT-526 was 0.7 and 0.8 h, respectively (range, 0.5-1 h). No dose-limiting toxicities were seen in any dogs (N = 242). Forty-two dogs receiving peptide had objective responses (&amp;gt;50% reduction in tumor size; n = 6) or significant disease stabilization. Most objective responses were seen after 60 days of exposure to the TSP-1 peptide. Antitumor activity was similar for both peptides and was seen in several histologies, including mammary carcinoma, head and neck carcinoma, soft tissue sarcoma, cutaneous T-cell lymphoma, and non–Hodgkin's lymphoma. Assessment of circulating endothelial cell populations in a small subset of dogs suggested that effective exposure to TSP-1 peptides may be associated with reductions in circulating endothelial cells. Conclusions: These results support the safety and activity of ABT-526 and ABT-510 in dogs with naturally occurring malignant cancers. Data from this preclinical trial support the development of TSP-1 mimetic peptides as anticancer agents.
Metabolism of circulating adenosine by the porcine isolated perfused lung.
Authors: P G Hellewell, J D Pearson
Journal: Circulation Research (1983)

Adenosine uptake was studied in the piglet isolated perfused lung by means of the single-circulation paired-tracer dilution technique. Adenosine was efficiently taken up from the pulmonary vascular bed, and the process was potently inhibited by dipyridamole. Following uptake, adenosine was incorporated into intracellular nucleotides, and at low perfusate concentrations, little or none of the incorporated radioactivity returned to the circulation. At higher concentrations, cellular uptake was saturable and products of intracellular catabolism (inosine and hypoxanthine) were returned to the circulation. Perfusion of low concentrations of adenosine after inhibition of pulmonary adenosine kinase led to a proportional decrease in the retention of nucleotides and to a release of inosine and hypoxanthine. A small proportion of adenosine was metabolised extracellularly by adenosine deaminase; this activity was not released from perfused lungs and is apparently an ecto-enzyme.