tbuckley/cabot-search huggingface dataset:
Intra-tumor Genetic Heterogeneity and Mortality in Head and Neck Cancer: Analysis of Data from The Cancer Genome Atlas
Authors: Edmund A. Mroz, Aaron M. Tward, Rebecca J. Hammon, Yin Ren, James W. Rocco
Journal: PLoS Medicine (2015)

Background Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH). Here, we examine data collected as part of a large, multi-institutional study to validate this measure and determine whether intra-tumor heterogeneity is itself related to mortality. Methods and Findings Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions. Initial pathologic diagnoses were between 1992 and 2011 (median, 2008). Median time to death for 131 deceased patients was 14 mo; median follow-up of living patients was 22 mo. Tumor MATH values were calculated from WES results. Despite the multiple head and neck tumor subsites and the variety of treatments, we found in this retrospective analysis a substantial relation of high MATH values to decreased overall survival (Cox proportional hazards analysis: hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3). This relation of intra-tumor heterogeneity to survival was not due to intra-tumor heterogeneity's associations with other clinical or molecular characteristics, including age, human papillomavirus status, tumor grade and TP53 mutation, and N classification. MATH improved prognostication over that provided by traditional clinical and molecular characteristics, maintained a significant relation to survival in multivariate analyses, and distinguished outcomes among patients having oral-cavity or laryngeal cancers even when standard disease staging was taken into account. Prospective studies, however, will be required before MATH can be used prognostically in clinical trials or practice. Such studies will need to examine homogeneously treated HNSCC at specific head and neck subsites, and determine the influence of cancer therapy on MATH values. Analysis of MATH and outcome in human-papillomavirus-positive oropharyngeal squamous cell carcinoma is particularly needed. Conclusions To our knowledge this study is the first to combine data from hundreds of patients, treated at multiple institutions, to document a relation between intra-tumor heterogeneity and overall survival in any type of cancer. We suggest applying the simply calculated MATH metric of heterogeneity to prospective studies of HNSCC and other tumor types.
Re: Re: Role of the Insulin-Like Growth Factors in Cancer Development and Progression
Authors: R. J. Collier, D. E. Bauman
Journal: JNCI Journal of the National Cancer Institute (2001)

We write to correct several misrepresentations and serious factual errors in the correspondence by Samuel S. Epstein (1). Among these are the statements that “the nation’s milk supply has been contaminated with excess IGF [insulin-like growth factor] levels;” “IGF . . . is readily absorbed from the gastrointestinal tract, and has growth promoting effects;” and “confirmation of these concerns by an international expert committee prompted the January 2000 European ban on the marketing and sale of rBGH [recombinant bovine growth hormone] milk.” The IGF-I content of milk from cattle treated with bovine somatotropin (rBST or rBGH) has been reviewed extensively by the U.S. Food and Drug Administration (2), the European Union (3), and the World Health Organization (WHO) (4). Comparisons of marketed milk indicate that there are no differences in the IGF-I concentrations between milk certified as derived from cows not treated with rBST and milk derived from cows receiving rBST (4). There is thus no evidence that milk marketed from herds treated with rBST has “excess IGF levels” as stated in (1). In addition, studies investigating the biologic activity of orally delivered IGF-I have uniformly demonstrated no change in serum IGF-I concentrations, even at oral doses greatly exceeding physiologic levels of IGF-I present in the digestive tract (5,6). Furthermore, the Joint Expert Committee on Food Additives (JECFA) of the United Nations Food and Agricultural Organization (FAO) (4) concluded that “any increase in the concentration of IGF-I in milk from rBST-treated cows is orders of magnitude lower than the physiological amounts produced in the gastrointestinal tract and in other parts of the body.” Finally, the European Union’s decision not to approve rBST for sale in member countries was based not on human health concerns but rather on animal issues (7). Milk and milk products from cattle treated with rBST are recognized as safe and may be marketed in European Union member countries (3).
Evaluation of the selection process of liver transplant candidates with alcoholic liver cirrhosis in Ikem, Prague
Authors: P. Wohl, E. Kostolná, J. Špicák, J. Šperl, H. Hrncárková, P. Trunecka, M. Ryska, F. Belina, K. Filip, Š. Vítko
Journal: Journal of Hepatology (2001)
Generation and Molecular Characterization of Head and Neck Squamous Cell Lines of Fanconi Anemia Patients
Authors: Hester J.T. van Zeeburg, Peter J.F. Snijders, Gerard Pals, Mario A.J.A. Hermsen, Martin A. Rooimans, Grover Bagby, Jean Soulier, Eliane Gluckman, Johan Wennerberg, C. René Leemans, Hans Joenje, Ruud H. Brakenhoff
Journal: Cancer Research (2005)

Abstract Patients with Fanconi anemia (FA) are prone to develop malignancies at an early age. Besides hematologic malignancies, squamous cell carcinomas in the anogenital region and head and neck are also frequently found in these patients. The aim of this study was to generate a panel of head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts of FA HNSCC, and to characterize these cell lines in comparison with a panel of seven cell lines from patients with sporadic HNSCC. Analyses have been done on sensitivity to DNA cross-linking agents, loss of heterozygosity profile, TP53 mutations, TP53 polymorphisms and the presence of human papillomavirus. Four FA HNSCC cell lines were established. Sensitivity to DNA cross-linking agents (cisplatin) in the FA HNSCC cell lines was on average 10 times higher as compared with the sporadic HNSCC cell lines. Human papillomavirus was not detected in any of the FA or sporadic cell lines. No differences were found in loss of heterozygosity pattern, TP53 mutation frequency and TP53 polymorphism between FA and sporadic HNSCC cell lines. This is the first report on the generation of squamous cell lines of FA patients. The FA HNSCC cell lines we have generated may be utilized for future studies and might aid in the development of new preventive therapies for FA patients. The genetic characteristics of these cell lines suggest that FA HNSCC are not very different from sporadic HNSCC, except for the sensitivity to cisplatin which is consistent with the known cellular FA phenotype.
Discovery and Characterization of Gut Microbiota Decarboxylases that Can Produce the Neurotransmitter Tryptamine
Authors: Brianna B. Williams, Andrew H. Van Benschoten, Peter Cimermancic, Mohamed S. Donia, Michael Zimmermann, Mao Taketani, Atsushi Ishihara, Purna C. Kashyap, James S. Fraser, Michael A. Fischbach
Journal: Cell Host & Microbe (2014)
The role of a relative age effect in the first winter Youth Olympic Games in 2012
Authors: Christian Raschner, Lisa Müller, Carolin Hildebrandt
Journal: British Journal of Sports Medicine (2012)

Background Owing to the separation into age groups at the first winter Youth Olympic Games (YOG), athletes differed in age by up to two years, leading to a potential relative age effect (RAE). Objective The purpose of this study was to define the role of the RAE in the first winter YOG with regard to sex, type of sport and performance. Methods The birth dates and anthropometric data of all 1021 athletes (557 male, 464 female, 14–19 years old) participating in 15 sports were analysed. A χ 2 test was used to assess the difference between the observed and expected birth distributions. ANOVA (analysis of variance) and Kruskal−Wallis analyses were used to investigate differences in anthropometrics. Results The birth date distribution of the overall sample was significantly different from an equal distribution, with an over-representation of athletes born shortly after the cut-off date (χ 2 =284.7, p&lt;0.001). A significant RAE was found in both male (χ 2 =245.1, p&lt;0.001) and female competitors (χ 2 =74.6, p&lt;0.001). An analysis based on the type of sport showed an RAE in all categories (strength—χ 2 =229.9, p&lt;0.001, endurance—χ 2 =60.4, p&lt;0.001 and technique-related sports χ 2 =25.2, p=0.001). Relatively older competitors were also over-represented among medal winners (χ 2 =47.9, p&lt;0.001). Relatively older male competitors were significantly taller (p=0.005) and heavier (p&lt;0.001) than younger competitors. No differences were found in female competitors. Conclusions The results suggest that relative age had a highly significant influence on participation in various sports regardless of sex. A possible strategy to reduce the RAE would be a fixed quota for each birth year within the two-year age group across events.
Synthetic Fc peptide-mediated regulation of the immune response. I. Characterization of the immunomodulating properties of a synthetic 23-amino acid peptide derived from the sequence of the CH3 domain of human IgG1.
Authors: E L Morgan, J E Shields, C S Campbell, R L Barton, G A Koppel, W O Weigle
Journal: The Journal of Experimental Medicine (1983)

A synthetic 23-amino acid peptide derived from the CH3 domain of human IgG1 was found to be a potent adjuvant as well as a polyclonal activator. The Fc peptide was found to enhance human and murine humoral, and T cell-mediated immune responses. Moreover, in vivo administration of Fc peptide enhanced murine natural killer cell activity. The synthetic Fc peptide was found to be more potent, on a molar basis, than native Fc fragments in inducing polyclonal antibody production and potentiating immune responses.
Letter: "Comprehensive psychiatric care".
Authors: A A Baker
Journal: BMJ (1976)

in its longest diameter was the only lesion detected.No evidence was found by which the latter could be aetiologically linked to the hydrops.In particular, there were no "vuln- erable" blood vessels of the placenta that might have been obstructed by the tumour, nor was this excessively vascular, so that an arteriovenous shunt effect was unlikely.Explanations such as protein sequestration by the tumour or unduly rapid increase in the vascular bed are within the realms of speculation.This association has not been reported before so far as I am aware (although Macafee et al; mention a case of mediastinal teratoma associated with hydrops) and I should be grateful to hear from any of your readers who know of a similar observation.
Factors Influencing Disease Expression in Hemochromatosis
Authors: Darrell H. G. Crawford, Lawrie W. Powell, June W. Halliday, Barbara A. Leggett
Journal: Annual Review of Nutrition (1996)

Genetic hemochromatosis is one of the most common inherited disorders in Caucasian populations. The disease frequency in Caucasian populations in Australia, Europe, and the United States is 1:300-400. The basic genetic defect remains unknown, although the hemochromatosis gene is closely linked to histocompatibility antigen (HLA) A, thus allowing early diagnosis in members of affected families. Many factors—environmental, genetic, and nongenetic in nature—influence the degree of iron loading in affected individuals. In particular, pathologic and physiologic blood loss and blood donation influence iron stores in hemochromatosis. The iron concentration in the liver is an important determinant of survival because a hepatic iron concentration in excess of 400 pmol/g dry weight is usually associated with cirrhosis. Patients with cirrhosis secondary to hemochromatosis are at risk of heptocellular carcinoma and complications of portal hypertension. The combination of improved awareness of the condition and the use of HLA typing to identify affected family members has led to earlier diagnosis and therapy, and to an improvement in overall survival
A young female with severe upper abdominal pain and profuse vomiting
Authors: H. Hardardottir, M. E. Keemers-Gels, A. Termeer, C. Rosman
Journal: European Respiratory Journal (2005)

A 23-yr-old female presented with progressive dyspnoea and epigastrical pain after 2 days of severe upper abdominal pain with heavy, profuse vomiting.There was no history of dysphagia or gastric reflux.
HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells
Authors: Lewis Z. Shi, Ruoning Wang, Gonghua Huang, Peter Vogel, Geoffrey Neale, Douglas R. Green, Hongbo Chi
Journal: The Journal of Experimental Medicine (2011)

Upon antigen stimulation, the bioenergetic demands of T cells increase dramatically over the resting state. Although a role for the metabolic switch to glycolysis has been suggested to support increased anabolic activities and facilitate T cell growth and proliferation, whether cellular metabolism controls T cell lineage choices remains poorly understood. We report that the glycolytic pathway is actively regulated during the differentiation of inflammatory TH17 and Foxp3-expressing regulatory T cells (Treg cells) and controls cell fate determination. TH17 but not Treg cell–inducing conditions resulted in strong up-regulation of the glycolytic activity and induction of glycolytic enzymes. Blocking glycolysis inhibited TH17 development while promoting Treg cell generation. Moreover, the transcription factor hypoxia-inducible factor 1α (HIF1α) was selectively expressed in TH17 cells and its induction required signaling through mTOR, a central regulator of cellular metabolism. HIF1α–dependent transcriptional program was important for mediating glycolytic activity, thereby contributing to the lineage choices between TH17 and Treg cells. Lack of HIF1α resulted in diminished TH17 development but enhanced Treg cell differentiation and protected mice from autoimmune neuroinflammation. Our studies demonstrate that HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells.
Oxidative Stress Mediates Apoptotic Changes Induced by Hyperglycemia in Human Tubular Kidney Cells
Authors: Daniela Verzola, Maria Bianca Bertolotto, Barbara Villaggio, Luciano Ottonello, Franco Dallegri, Francesca Salvatore, Valeria Berruti, Maria Teresa Gandolfo, Giacomo Garibotto, Giacomo Deferrari
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Reactive oxygen species (ROS) are important mediators for several biologic responses, including apoptosis. The present study evaluated the time course of changes in intracellular ROS production and apoptosis-related proteins, as well as apoptotic changes in human tubular proximal cells (HK-2 cells) exposed to hyperglycemia. Apoptosis (annexin V binding), ROS formation (fluorescence probe dichlorofluorescin diacetate and FACScan flow cytometry), and X chromosome–linked protein (XIAP; Western blot) were studied in HK-2 cells grown in a medium containing normal (NG) or high glucose (HG) concentrations (5.5 or 30 mM, respectively) for 18 to 48 h. HG promoted an increase (65% at 18 h and 73% at 24 h; <i>P</i> &lt; 0.05 <i>versus</i> NG) in intracellular ROS generation. At 18 h, the NF-kB binding activity (evaluated by electrophoretic mobility-shift assay) was suppressed by HG. At the same time, the expression of NF-kB–induced antiapoptotic XIAP was reduced in HG-treated cells. Apoptotic changes were observed at 48 h (34 ± 7% in HG versus 10 ± 3% in NG; <i>P</i> &lt; 0.001). Changes in ROS production at 24 h predicted changes in the apoptotic index at 48 h (<i>r</i> = 0.96, <i>P</i> &lt; 0.0001). These results suggest that hyperglycemia induces apoptotic changes in human tubular cells via an increase in oxidative stress and that a downregulation of antiapoptotic protein XIAP is a component of this response.
Closure of the Inguinal Canal in Treatment of Hernia
Authors: H. S. K. Singha
Journal: BMJ (1963)

as they were based on the results of a single meal of iron-fortified bread given to normal subjects.The results of the experiment reported here give no evidence that additional fortification of flour is of therapeutic value; they also raise doubts about the value of the present level of fortification with ferrum redactum in this country.Summary Bread made from flour fortified with 60 mg. of ferrum redactum per 100 g. of flour was given for six months to two groups of 53 and 55 female patients in long-stay units of a mental hospital.Each patient received about 80 mg. of elemental iron per day.One group was given a vitamin C supplement twice a day for the last two months of the trial.A further group of 52 patients received the same total amount of elemental iron in tablet form as ferrous gluconate, and another group of 99 patients received no iron therapy.All groups were comparable with regard to age and haemoglobin level at the commencement of the trial.No significant (at P<0.05) increase in mean haemo- globin level was experienced by either group given fortified bread, but the group given tablets of ferrous gluconate did experience a significant mean increase.Patients with an initial haemoglobin level of less than 12.5 g./100 ml. in the group given fortified bread but no vitamin C experienced a significant increase in mean haemoglobin, but this increase was almost identical with that experienced by comparable patients in the control group.The patients with lower initial haemoglobin levels who received ferrous gluconate showed a signi- ficant mean increase of 1.60 + 0.30 g. over the six months, which was significantly in excess of corre- sponding changes in all other similar patients.These results are discussed and the therapeutic value of fortification of flour with ferrum redactum at a high level is considered; the relevance of the findings to the present statutory fortification of flour is indicated.I would like to thank Professor J. Pemberton, who initiated this study, for advice, and Dr. C. B. Robinson and the nursing staff for the hospital for their willing co-operation.I am indebted to the directors of Messrs. Inglis and Co
Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients
Authors: J. Wenzel, S. Brahler, R. Bauer, T. Bieber, T. Tuting
Journal: British Journal of Dermatology (2005)

Journal Article Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients Get access J. Wenzel, J. Wenzel Department of Dermatology, University of Bonn, Sigmund‐Freud‐Strasse 25, 53105 Bonn, Germany Joerg Wenzel. E‐mail: joerg.wenzel@ukb.uni‐bonn.de Search for other works by this author on: Oxford Academic Google Scholar S. Brähler, S. Brähler Department of Dermatology, University of Bonn, Sigmund‐Freud‐Strasse 25, 53105 Bonn, Germany Search for other works by this author on: Oxford Academic Google Scholar R. Bauer, R. Bauer Department of Dermatology, University of Bonn, Sigmund‐Freud‐Strasse 25, 53105 Bonn, Germany Search for other works by this author on: Oxford Academic Google Scholar T. Bieber, T. Bieber Department of Dermatology, University of Bonn, Sigmund‐Freud‐Strasse 25, 53105 Bonn, Germany Search for other works by this author on: Oxford Academic Google Scholar T. Tüting T. Tüting Department of Dermatology, University of Bonn, Sigmund‐Freud‐Strasse 25, 53105 Bonn, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 1, 1 July 2005, Pages 157–162, https://doi.org/10.1111/j.1365-2133.2005.06552.x Published: 01 July 2005 Article history Accepted: 22 September 2004 Published: 01 July 2005
Screening of asymptomatic elite youth hockey players: clinical and MRI exam
Authors: M J Philippon, R F LaPrade, K K Briggs, J D Stull
Journal: British Journal of Sports Medicine (2011)

Background Ice hockey players are reportedly at increased risk to suffer hip injuries. This may be due to repetitive hip positions during the ice hockey skate stride. Objective To determine if specific tests used during a screening program can identify youth hockey players who are at risk of acetabular labral tears due to femoroacetabular impingement (FAI). Design Prospective screening study. Setting Clinical centre screened elite youth hockey players. Participants 20 asymptomatic male (average age of 17.6 SD=0.5) ice hockey players who had signed IRB approved consent. Assessment of risk factors Participants underwent impingement testing, Flexion Abduction External Rotation (FABER) test, and range of motion and hip strength assessment prior to an MRI (3T) to determine hip alpha angle (AA) and labral pathology. Main outcome measurements Positive clinical findings of impingement correlate with the presence of labral pathology and high AA. Results 14 players had a positive clinical exam (+impingement test or+FABER test or decreased hip internal rotation). Players with a positive clinical exam had a significantly higher AA compared to those with no positive signs (68° vs 61°; p&lt;0.025). Players with a positive clinical exam were 12.5 times (95% CI 1.1 to 143) more likely to have an AA 65° or greater. 12 of the 14 participants with a positive clinical exam also had partial acetabular labral tears. Conclusion With this screening protocol, we were able to identify those patients with higher AA, which are considered at high risk. These players also demonstrated labral tears on MRI. We recommend that hip screening utilizing the impingement test, FABER test, and assessment of hip internal rotation be conducted as the initial screening of athletes with hip pain to assess for symptomatic FAI.