tbuckley/cabot-search huggingface dataset:
Effectiveness of Implementing the Agency for Healthcare Research and Quality Smoking Cessation Clinical Practice Guideline: A Randomized, Controlled Trial
Authors: D. A. Katz, D. R. Muehlenbruch, R. L. Brown, M. C. Fiore, T. B. Baker
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: The Agency for Healthcare Research and Quality (AHRQ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit. Methods: We conducted a randomized, controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin (four test sites, four control sites) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period (June 16, 1999, to June 20, 2000) or the intervention period (from June 21, 2000, to May 3, 2001). After collecting baseline data, staff at test sites implemented the intervention over a 2-month period. The intervention included a tutorial for intake clinicians, group and individual performance feedback for intake clinicians, use of a modified vital signs stamp, an offer of free nicotine replacement therapy, and proactive telephone counseling. Staff at control sites received only general information about the AHRQ Guideline. Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessments. Hierarchical logistic regression models were used to estimate the odds ratios (ORs) for treatment assignment after adjustment for patient characteristics. All statistical tests were two-sided. Results: There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period. Among participants treated during the intervention period, those at test sites were more likely than those at control sites to report being abstinent at the 2-month (16.4% versus 5.8%; adjusted OR = 3.3, 95% confidence interval [CI] = 1.9 to 5.6; P<.001) and 6-month (15.4% versus 9.8%; adjusted OR = 1.7, 95% CI = 1.2 to 2.6; P = .009) follow-up assessments and to report continuous abstinence, that is, abstinence at both 2 and 6 months (10.9% versus 3.8%; adjusted OR = 3.4, 95% CI = 1.8 to 6.3; P<.001). Conclusion: Implementation of a guideline-based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers.
Clinicopathologic Findings Predictive of Relapse in Children With Stage III Favorable-Histology Wilms Tumor
Authors: Peter F. Ehrlich, James R. Anderson, Michael L. Ritchey, Jeffrey S. Dome, Daniel M. Green, Paul E. Grundy, Elizabeth J. Perlman, John A. Kalapurakal, Norman E. Breslow, Robert C. Shamberger
Journal: Journal of Clinical Oncology (2013)

Stage III designation in NWTS-5 (National Wilms Tumor Study-5) was determined by four pathologic criteria: positive lymph nodes (LNs), peritoneal implants, residual disease, and tumor rupture. The objective of this study was to determine the prognostic significance of each of the stage III criteria.Children with stage III Wilms tumor (WT) treated in NWTS-5 were assessed for event-free (EFS) and overall survival (OS). Sites of relapse and molecular status of tumors are reported. EFS and OS are reported 8 years after diagnosis.There were 569 patients with local stage III favorable-histology (FH) WT in this analysis, of whom 109 had overall stage IV disease. LN involvement alone was the most frequent criterion for stage III designation (38%), followed by microscopic residual disease alone (20%), microscopic residual disease and LN involvement (14%), and spill or soilage alone (9%). The 8-year EFS and OS estimates for all patients with local stage III FHWT were 82% and 91%, respectively. Multivariate analysis demonstrated that both LN involvement (relative risk, 1.89; P = .005) and microscopic residual disease (relative risk, 1.87; P = .007) were predictive of EFS, and OS results were similar. There was no apparent difference in pattern of relapse according to stage III subtype. The rate of loss of heterozygosity was higher (6%) for those with positive LNs than for those without (2%; P = .05).LN involvement and microscopic residual are the stage III criteria highly predictive of EFS and OS for patients with stage III FHWT. It is possible that in future studies, patients with different stage III criteria may receive different therapies.
Population-Level Analyses Indirectly Reveal Cryptic Sex and Life History Traits of Pseudoperkinsus tapetis (Ichthyosporea, Opisthokonta): A Unicellular Relative of the Animals
Authors: W. L. Marshall, M. L. Berbee
Journal: Molecular Biology and Evolution (2010)

We use population genetics to detect the molecular footprint of a sexual cycle, of a haploid vegetative state, and of lack of host specificity in Pseudoperkinsus tapetis, a marine unicellular relative of the animals. Prior to this study, complete life cycles were not known for any of the unicellular lineages sharing common ancestry with multicellular animals and fungi. We established the first collection of conspecific cultures of any member from the unicellular opisthokont lineage ichthyosporea, isolating 126 cultures of P. tapetis from guts of marine invertebrates ranging from clams to sea cucumbers. We sequenced fragments of the elongation factor alpha-like (EFL) and heat-shock protein 70 (HSP70) genes for a subset of our isolates. Absence of heterozygotes from the EFL locus in 52 isolates provided evidence for haploidy. Phylogenetic incongruence and a lack of support for linkage between two loci from 34 sequenced isolates signified a history of recombination consistent with a sexual cycle. Shared haplotypes in different invertebrate species showed that P. tapetis was not host specific. Based on estimates of the frequency of sex and on observations of cultures, we propose that P. tapetis is transmitted between hosts via asexual endospores. New protists are continually being discovered, and, as this study illustrates, analysis of culturable collections from natural habitats can transform a species from a near unknown to a model system for better understanding the evolution of life histories.
Lifetime Costs of Complications Resulting From Type 2 Diabetes in the U.S.
Authors: J. Jaime Caro, Alexandra J. Ward, Judith A. O’Brien
Journal: Diabetes Care (2002)

OBJECTIVE—To model the lifetime costs associated with complications of type 2 diabetes. RESEARCH DESIGN AND METHODS—A cohort of 10,000 patients with diabetes was simulated using a model based on existing epidemiological studies. Complication rates were estimated for various stages of macrovascular disease, nephropathy, retinopathy, neuropathy, and hypoglycemia. At the beginning of the simulation, patients were assumed to have been treated for 5 years and have a mean HbA1c of 8.4. From the U.K. Prospective Diabetes Study, it was estimated that on current therapies, the HbA1c would drift upward on average 0.15% per year. Direct medical costs of managing each complication were estimated (in 2000 U.S. dollars) from all-payor databases, surveys, and literature. RESULTS—Macrovascular disease was estimated to be the largest cost component, accounting for 85% of cumulative costs of complications over the first 5 years. The costs of complications were estimated to be $47,240 per patient over 30 years, on average. The management of macrovascular disease is estimated to be the largest cost component, accounting for 52% of the costs; nephropathy accounts for 21%, neuropathy accounts for 17%, and retinopathy accounts for 10% of the costs of complications. CONCLUSIONS—The complications of diabetes account for substantial costs, with management of macrovascular disease being the largest and earliest. If improving glycemic control prevents complications, it will reduce these costs.
PTU-141 Gastric Intestinal Metaplasia: A Retrospective Analysis In A District General Hospital In The United Kingdom
Authors: A Singanayagam, N Chatrath, L Pee, A Loganayagam
Journal: Gut (2014)

Introduction Gastric intestinal metaplasia (IM) is part of a carcinogenesis sequence leading to gastric cancer. Recent evidence-based European Society of Gastrointestinal Endoscopy (ESGE) guidelines highlight additional risk factors, such as extensive intragastric distribution of IM and the presence of Helicobacter pylori . The former is identified with ≥2 antral and ≥2 corpus biopsies, involving the greater and lesser curvature, and warrants three-yearly surveillance endoscopies. The latter should be eradicated to slow carcinogenesis progression. Methods Using keywords “intestinal metaplasia”, the histology database for the Queen Elizabeth Hospital, South London, was reviewed over 2000–11 to identify patients with IM on gastric biopsy. Gastro-oesophageal junctional IM was excluded. The number and site of biopsies taken and the presence of H. pylori was identified. The terminology used, with regards to “extensive” and “focal” IM, was compared with the suggestions from the ESGE guidelines. To investigate the development of cancer in patients with IM, histology and upper gastrointestinal cancer databases were compared. Results 175 patients with gastric IM were identified. Of these, only one patient developed gastric cancer. Helicobacter pylori was associated with 20/175 (11.4%) of gastric IM biopsies. After review of pathology reports, in 37/175 (21.1%) of cases with gastric IM, the pathologist did not receive sufficient clinical information specifying the site of the biopsies. Of those where the biopsy site was specified, only 10/138 (7.2%) had sufficient biopsies. The term “extensive” was used in 27/175 (15.4%) pathology reports, despite either insufficient number or non-specified location of biopsies. Conclusion This study identified 175 patients with gastric intestinal metaplasia over 2000–2011. One patient developed gastric adenocarcinoma after 8 years. Since surveillance endoscopy is not routine practice in the Trust, all biopsies were incidental findings. This study suggests that, where biopsy site details were provided, only 7.2% of patients were adequately biopsied. Remaining cases should have repeat biopsies to decide on surveillance. “Extensive metaplasia” refers to a wide intragastric distribution of IM to include the antrum and corpus. We identified discrepant use of nomenclature in pathology reporting in 15.4%. Helicobacter pylori was associated in 11.4%, where ESGE advocates its eradication. This study reveals further work is needed to risk stratify and survey this important pre-cancerous condition. Reference Dinis-Ribeiro M, Areia M, de Vries A, Marcos-Pinto R, Monteiro-Soares M, O’Connor A, et al . Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE). Endoscopy 2011 Dec 23;44(01):74–94 Disclosure of Interest None Declared.
Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes
Authors: S Sobue, T Iwasaki, C Sugisaki, K Nagata, R Kikuchi, M Murakami, A Takagi, T Kojima, Y Banno, Y Akao, Y Nozawa, R Kannagi, M Suzuki, A Abe, T Naoe, T Murate
Journal: Leukemia (2006)
Elevated Intestinal Interleukin-13 Promotes Intestinal Epithelial Barrier Dysfunction
Authors: D.X. Wu, R.E. Ahrens, K.R. Groschwitz, H.N. Osterfield, P.S. Foster, F.D. Finkelman, K.I. Matthaei, S.P. Hogan
Journal: Journal of Allergy and Clinical Immunology (2009)
Dual Targeting of Wild-Type and Mutant p53 by Small Molecule RITA Results in the Inhibition of N-Myc and Key Survival Oncogenes and Kills Neuroblastoma Cells <i>In Vivo</i> and <i>In Vitro</i>
Authors: Mikhail Burmakin, Yao Shi, Elisabeth Hedström, Per Kogner, Galina Selivanova
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Restoration of the p53 function in tumors is a promising therapeutic strategy due to the high potential of p53 as tumor suppressor and the fact that established tumors depend on p53 inactivation for their survival. Here, we addressed the question whether small molecule RITA can reactivate p53 in neuroblastoma and suppress the growth of neuroblastoma cells in vitro and in vivo. Experimental Design: The ability of RITA to inhibit growth and to induce apoptosis was shown in seven neuroblastoma cell lines. Mechanistic studies were carried out to determine the p53 dependence and the molecular mechanism of RITA-induced apoptosis in neuroblastoma, using cell viability assays, RNAi silencing, co-immunoprecipitation, qPCR, and Western blotting analysis. In vivo experiments were conducted to study the effect of RITA on human neuroblastoma xenografts in mice. Results: RITA induced p53-dependent apoptosis in a set of seven neuroblastoma cell lines, carrying wild-type or mutant p53; it activated p53 and triggered the expression of proapoptotic p53 target genes. Importantly, p53 activated by RITA inhibited several key oncogenes that are high-priority targets for pharmacologic anticancer strategies in neuroblastoma, including N-Myc, Aurora kinase, Mcl-1, Bcl-2, Wip-1, MDM2, and MDMX. Moreover, RITA had a strong antitumor effect in vivo. Conclusions: Reactivation of wild-type and mutant p53 resulting in the induction of proapoptotic factors along with ablation of key oncogenes by compounds such as RITA may be a highly effective strategy to treat neuroblastoma. Clin Cancer Res; 19(18); 5092–103. ©2013 AACR.
On the Conduction of Physical Signs in Diseases of the Lungs
Authors: E. M. Skerritt
Journal: BMJ (1884)

7Rlow M I months, p.nd having convalesced.. went about for three weeks,4wkea pain eppesred at the umbilicus, which was not increased after taking food.4oh kept about for three weeks, when she, was compelkedtotake to her bed°1 She then had diarrhcea, without much pai-n or toeemuss and for *l'e weeks had vomiting, which, latterly, had been extreme.When ;VPXitted, she had an anxious face, and was very thin.There was pai< t the umbilicus, and upwards along the sternum, and across fob epigastrium.On February 5th, the bowels were opened, and tIAsnmotion natural.She had no vomiting.On the 8th, she vomited After eating bread and butter.On the 11th, the pain was const'*nt; the bowels were opened naturally ; there was no mucus in the mot¼'?JI0 On the 14th, the pain was constant,' but aggravated in paroWhks, with vomiting.OF the 18th, compound colocynth pill was given, t'hich operated quickly, and diarrhoea set in, which lasted until the 22nd.On March 7th, at 8 A. M., sudden intense pain arose, followed in one hour by vomiting., Morphia-injections and poultices relieved the pain, but tht 'patLent was collapsed at 2, and died at 5 P.M.A pos& V.W..rtem examilanation was made (88).The peritoneum contained iauch thin, purulent fluid, and one coil of bowel looked of a yellow 'aoloar.Many coils were greatly distended.After removal, when laid wpen, they measured five inches and a half.Below the umbilicus, an i.ntussusception was seen of the small intestine, two or three feet above J.he cncum.On this being laid open, it was found that the lower end o! f the intussuscepted mass had a solid tumour hanging from it by a
Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression
Authors: Swati Biswas, Marta Guix, Cammie Rinehart, Teresa C. Dugger, Anna Chytil, Harold L. Moses, Michael L. Freeman, Carlos L. Arteaga
Journal: Journal of Clinical Investigation (2007)

We investigated whether TGF-β induced by anticancer therapies accelerates tumor progression. Using the MMTV/PyVmT transgenic model of metastatic breast cancer, we show that administration of ionizing radiation or doxorubicin caused increased circulating levels of TGF-β1 as well as increased circulating tumor cells and lung metastases. These effects were abrogated by administration of a neutralizing pan–TGF-β antibody. Circulating polyomavirus middle T antigen–expressing tumor cells did not grow ex vivo in the presence of the TGF-β antibody, suggesting autocrine TGF-β is a survival signal in these cells. Radiation failed to enhance lung metastases in mice bearing tumors that lack the type II TGF-β receptor, suggesting that the increase in metastases was due, at least in part, to a direct effect of TGF-β on the cancer cells. These data implicate TGF-β induced by anticancer therapy as a prometastatic signal in tumor cells and provide a rationale for the simultaneous use of these therapies in combination with TGF-β inhibitors.
The impact of phlebotomy in nonalcoholic fatty liver disease: A prospective, randomized, controlled trial
Authors: Leon A. Adams, Darrell H. Crawford, Katherine Stuart, Michael J. House, Timothy G. St. Pierre, Malcolm Webb, Helena L.I. Ching, Jenny Kava, Michael Bynevelt, Gerry C. MacQuillan, George Garas, Oyekoya T. Ayonrinde, Trevor A. Mori, Kevin D. Croft, Xianwa Niu, Gary P. Jeffrey, John K. Olynyk
Journal: Hepatology (2014)

Iron is implicated in the pathogenesis of liver injury and insulin resistance (IR) and thus phlebotomy has been proposed as a treatment for nonalcoholic fatty liver disease (NAFLD). We performed a prospective 6‐month randomized, controlled trial examining the impact of phlebotomy on the background of lifestyle advice in patients with NAFLD. Primary endpoints were hepatic steatosis (HS; quantified by magnetic resonance imaging) and liver injury (determined by alanine aminotransaminase [ALT] and cytokeratin‐18 [CK‐18]). Secondary endpoints included insulin resistance measured by the insulin sensitivity index (ISI) and homeostasis model of assessment (HOMA), and systemic lipid peroxidation determined by plasma F2‐isoprostane levels. A total of 74 subjects were randomized (33 phlebotomy and 41 control). The phlebotomy group underwent a median (range) of 7 (1‐19) venesection sessions and had a significantly greater reduction in ferritin levels over 6 months, compared to controls (−148 ± 114 vs. −38 ± 89 ng/mL; P &lt; 0.001). At 6 months, there was no difference between phlebotomy and control groups in HS (17.7% vs. 15.5%; P = 0.4), serum ALT (36 vs. 46 IU/L; P = 0.4), or CK‐18 levels (175 vs. 196 U/L; P = 0.9). Similarly, there was no difference in end‐of‐study ISI (2.5 vs. 2.7; P = 0.9), HOMA (3.2 vs. 3.2; P = 0.6), or F2‐isoprostane levels (1,332 vs. 1,190 pmmol/L; P = 0.6) between phlebotomy and control groups. No differences in any endpoint were noted in patients with hyperferritinemia at baseline. Among patients undergoing phlebotomy, there was no correlation between number of phlebotomy sessions and change in HS, liver injury, or IR from baseline to end of study. Conclusion : Reduction in ferritin by phlebotomy does not improve liver enzymes, hepatic fat, or IR in subjects with NAFLD. (H epatology 2015;61:1555–1564)
JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma
Authors: Adam D. Durbin, Gino R. Somers, Michael Forrester, Malgorzata Pienkowska, Gregory E. Hannigan, David Malkin
Journal: Journal of Clinical Investigation (2009)

Although most reports describe the protein kinase integrin-linked kinase (ILK) as a proto-oncogene, occasional studies detail opposing functions in the regulation of normal and transformed cell proliferation, differentiation, and apoptosis. Here, we demonstrated that ILK functions as an oncogene in the highly aggressive pediatric sarcoma alveolar rhabdomyosarcoma (ARMS) and as a tumor suppressor in the related embryonal rhabdomyosarcoma (ERMS). These opposing functions hinge on signaling through a noncanonical ILK target, JNK1, to the proto-oncogene c-Jun. RNAi-mediated depletion of ILK induced activation of JNK and its target, c-Jun, resulting in growth of ERMS cells, whereas in ARMS cells, it led to loss of JNK/c-Jun signaling and suppression of growth both in vitro and in vivo. Ectopic expression of the fusion gene characteristic of ARMS (paired box 3-forkhead homolog in rhabdomyosarcoma [PAX3-FKHR]) in ERMS cells was sufficient to convert them to an ARMS signaling phenotype and render ILK activity oncogenic. Furthermore, restoration of JNK1 in ARMS reestablished a tumor-suppressive function for ILK. These findings indicate what we believe to be a novel effector pathway regulated by ILK, provide a mechanism for interconversion of oncogenic and tumor-suppressor functions of a single regulatory protein based on the genetic background of the tumor cells, and suggest a rationale for tailored therapy of rhabdomyosarcoma based on the different activities of ILK.
Stress-Related Signaling Pathways in Lethal and Nonlethal Prostate Cancer
Authors: Donghao Lu, Jennifer A. Sinnott, Unnur Valdimarsdóttir, Fang Fang, Travis Gerke, Svitlana Tyekucheva, Michelangelo Fiorentino, Mats Lambe, Howard D. Sesso, Christopher J. Sweeney, Kathryn M. Wilson, Edward L. Giovannucci, Massimo Loda, Lorelei A. Mucci, Katja Fall
Journal: Clinical Cancer Research (2015)

Recent data suggest that neuroendocrine signaling may influence progression in some cancers. We aimed to determine whether genes within the five major stress-related signaling pathways are differentially expressed in tumor tissue when comparing prostate cancer patients with lethal and nonlethal disease.
A neuron doctrine in the philosophy of neuroscience
Authors: Ian Gold, Daniel Stoljar
Journal: Behavioral and Brain Sciences (1999)

Many neuroscientists and philosophers endorse a view about the explanatory reach of neuroscience (which we will call the neuron doctrine) to the effect that the framework for understanding the mind will be developed by neuroscience; or, as we will put it, that a successful theory of the mind will be solely neuroscientific. It is a consequence of this view that the sciences of the mind that cannot be expressed by means of neuroscientific concepts alone count as indirect sciences that will be discarded as neuroscience matures. This consequence is what makes the doctrine substantive, indeed, radical. We ask, first, what the neuron doctrine means and, second, whether it is true. In answer to the first question, we distinguish two versions of the doctrine. One version, the trivial neuron doctrine, turns out to be uncontroversial but unsubstantive because it fails to have the consequence that the nonneuroscientific sciences of the mind will eventually be discarded. A second version, the radical neuron doctrine, does have this consequence, but, unlike the first doctrine, is highly controversial. We argue that the neuron doctrine appears to be both substantive and uncontroversial only as a result of a conflation of these two versions. We then consider whether the radical doctrine is true. We present and evaluate three arguments for it, based either on general scientific and philosophical considerations or on the details of neuroscience itself, arguing that all three fail. We conclude that the evidence fails to support the radical neuron doctrine.