tbuckley/cabot-search huggingface dataset:
Stage one seminoma: Evidence based guidelines for follow up
Authors: J. M. Martin, T. Panzarella, D. R. Zwahlen, P. W. Chung, P. Warde
Journal: Journal of Clinical Oncology (2006)

4546 Background: Several management strategies are used following ochiectomy for stage one seminoma (SOS) of the testis. The aim of this systematic review (SR) is to provide evidence based guidelines for the follow-up (FU) schedule for each strategy regarding investigations required, frequency of assessment and overall duration. Methods: A SR of all prospective studies in SOS published since 1980 in MEDLINE, EMBASE and the Cochrane database was performed in November 2005. Data was extracted regarding the time, location and method of detection of first relapses, duration of FU, relapse free rates, and numbers of patients at risk. Five strategies were identified: Surveillance (S), Extended-field Radiotherapy (EFRT), Para-aortic Radiotherapy (PART) and either one (C1) or two (C2) cycles of Carboplatin chemotherapy. For each strategy Kaplan-Meier relapse free estimates were used to calculate weighted mean cumulative hazards of relapse over time. These were used to calculate yearly weighted mean relapse hazards. Weights used were based on numbers of patients at risk in each trial. Results: Fifteen prospective studies with a total of 5277 patients were identified. Actuarial relapse data was available in 4185 (79.3%) patients and 4850 (91.9%) had the location of relapse documented. Method of relapse detection was infrequently reported. The median time to relapse with all strategies was 12–16 months. Annual hazard ratios for relapse decreased with increasing length of FU and relapse location depended on the strategy used ( Table ). Conclusions: 1. The investigations performed need to reflect locations at risk of relapse. This should include computerised tomography (CT) of the abdomen and pelvis for Survillance and adjuvant Carboplatin, with CT of the pelvis only for Para-aortic RT. 2. Long term FU data on patients treated with Carboplatin is not available, and further FU is necessary. 3. Frequency of FU should reflect the annual hazard of relapse. We suggest 3 times per year when the risk is &gt;5%, 2 times per year when the risk is 1–5%, and annually until the risk is &lt;0.3%. [Table: see text] No significant financial relationships to disclose.
P161Two cardioprotective regimens of chronic intermittent hypoxia differ in activation of antioxidant systems
Authors: D Kasparova, J Neckar, F Kolar, J Novotny, O Novakova, J Zurmanova
Journal: Cardiovascular Research (2014)

Purpose: We have shown that long-term adaptation to intermittent normobaric hypoxia (INH) or to intermittent hypobaric hypoxia (IHH) for 8 h per day improves myocardial tolerance to acute ischemia-reperfusion injury. Reactive oxygen species formed during hypoxic exposures play an important role in the induction of protective cardiac phenotype.
Trends in Coronary Revascularization Procedures Among Medicare Beneficiaries Between 2008 and 2012
Authors: Steven D. Culler, Aaron D. Kugelmass, Phillip P. Brown, Matthew R. Reynolds, April W. Simon
Journal: Circulation (2014)

This study reports on the trends in the volume and outcomes of coronary revascularization procedures performed on Medicare beneficiaries between 2008 and 2012.This retrospective study identifies all Medicare beneficiaries undergoing a coronary revascularization procedure: coronary artery bypass graft surgery or percutaneous coronary intervention (PCI) performed in either the nonadmission or inpatient setting. International Classification of Diseases, 9th Revision, Clinical Modification procedure codes (inpatient setting) and Current Procedural Terminology and Ambulatory Payment Classification codes (nonadmission) were used to identify revascularizations. The study population consists of 2,768,007 records. This study finds that the rapid growth in nonadmission PCIs performed on Medicare beneficiaries (60,405-106,495) has been more than offset by the decrease in PCI admissions (363,384-295,434) during the study period. There also were >18,000 fewer coronary artery bypass graft admissions in 2012 than in 2008. This study finds lower observed mortality rates (3.7%-3.2%) among Medicare beneficiaries undergoing any coronary artery bypass graft surgery and higher observed mortality rates (1.7%-1.9%) for Medicare beneficiaries undergoing any PCI encounter. This study also finds a growth in the number of facilities performing revascularization procedures during the study period: 268 (20.2%) more sites were performing nonadmission PCIs; 136 (8.2%) more sites were performing inpatient PCIs; and 19 (1.6%) more sites were performing coronary artery bypass graft surgery.The total number of revascularization procedures performed on Medicare beneficiaries peaked in 2010 and declined by >4% per year in 2011 and 2012. Observed mortality rates among all Medicare beneficiaries undergoing any coronary revascularization remained between 2.1% and 2.2% annually during the study period.
Ichthyosis vulgaris: novel<i>FLG</i>mutations in the German population and high presence of CD1a+ cells in the epidermis of the atopic subgroup
Authors: V. Oji, N. Seller, A. Sandilands, R. Gruber, J. Gerß, U. Hüffmeier, H. Hamm, S. Emmert, K. Aufenvenne, D. Metze, T. Luger, K. Loser, I. Hausser, H. Traupe, W.H.I. McLean
Journal: British Journal of Dermatology (2009)

Ichthyosis vulgaris (IV) is a genetic disorder with a prevalence of 1:250-1000 caused by filaggrin (FLG) mutations, which also predispose to atopic diseases.To study the genotype/phenotype relationship in IV and to analyse whether the suggested skin barrier defect is associated with differences of epidermal dendritic cells.We evaluated a cohort of 26 German patients with IV, established an IV severity score and analysed epidermal ultrastructure, histology, filaggrin and CD1a antigens. Mutations were screened by restriction enzyme analysis. Particular sequencing techniques allowed the complete FLG analysis to reveal novel mutations.The combined null allele frequency of R501X and 2282del4 was 67.3%. Patients also showed the mutations S3247X and R2447X as well as five novel FLG mutations: 424del17 and 621del4 (profilaggrin S100 domain), 2974delGA (repeat 2), R3766X (repeat 10(1)) and E4265X (repeat 10(2)). Their combined allele frequency in controls was <0.7%. No mutation was found in one IV patient, all in all approximately 27% were heterozygous, and the majority (approximately 69%) showed two null alleles. The IV severity score and ultrastructure showed a significant correlation with genotypes. Interestingly, CD1a cell counts showed a significant difference between nonatopic and atopic IV patients both with eczema and without eczema.We confirm that the mutations R501X and 2282del4 represent the most frequent genetic cause in German IV patients. The novel mutations are probably population and family specific. The observed differences of CD1a cells support the hypothesis that there is a barrier defect that predisposes to atopic manifestations, possibly independent of atopic eczema.
Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA
Authors: Tim Forshew, Muhammed Murtaza, Christine Parkinson, Davina Gale, Dana W. Y. Tsui, Fiona Kaper, Sarah-Jane Dawson, Anna M. Piskorz, Mercedes Jimenez-Linan, David Bentley, James Hadfield, Andrew P. May, Carlos Caldas, James D. Brenton, Nitzan Rosenfeld
Journal: Science Translational Medicine (2012)

Sizable genomic regions were screened and low-frequency mutations were identified in circulating DNA of cancer patients using tagged-amplicon deep sequencing (TAm-Seq).
Transatrial repair of double-outlet right ventricle in infants.
Authors: D A Goor, C Massini, A Shem-Tov, H N Neufeld
Journal: Thorax (1982)

In three infant cases of double outlet right ventricle (DORV), two with normally related great arteries (NGA) and one with side-by-side great arteries, a transatrial repair was carried out. In all three cases, the results were excellent. It is concluded that in the small baby with DORV with NGA and in DORV with side-by-side great arteries with a hypoplastic crista, a transatrial repair should be successful. This is dependent on the VSD being in the perimembranous (and, therefore, subaortic) location and on the absence of infundibular pulmonary stenosis. In all other varieties of DORV the repair should probably be done through the ventricle.
CRYSTAL-INDUCED INFLAMMATION IN CANINE JOINTS
Authors: Daniel J. McCarty, Paulding Phelps, Jacob Pyenson
Journal: The Journal of Experimental Medicine (1966)

Injection of sodium urate or calcium pyrophosphate crystals into the stifle joints of anesthetized dogs almost invariably induced an acute exudative response. This response was quantified by serial measurements of intra-articular pressure, pH and leukocyte concentration. Pressure rose progressively and reflected intra-articular volume increase. The hydrogen ion concentration increased as the reaction progressed and correlated in a given exudate with the leukocyte concentration. Analysis of sequential physiologic and biochemical changes occurring in this model of crystal-induced inflammation may provide insight into the mechanisms of acute gouty arthritis in man.
Herpetiform napkin dermatitis: napkin dermatitis simulating an acute herpes simplex infection
Authors: R.A.C. Graham-Brown, D.M. Lister, D.A. Burns
Journal: British Journal of Dermatology (1986)

Journal Article Herpetiform napkin dermatitis: napkin dermatitis simulating an acute herpes simplex infection Get access R.A.C. Graham‐Brown, R.A.C. Graham‐Brown Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.M. Lister, D.M. Lister Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.A. Burns D.A. Burns Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 114, Issue 6, 1 June 1986, Pages 746–747, https://doi.org/10.1111/j.1365-2133.1986.tb04888.x Published: 01 June 1986
Quaternary Epitopes of α345(IV) Collagen Initiate Alport Post-Transplant Anti-GBM Nephritis
Authors: Florina Olaru, Wentian Luo, Xu-Ping Wang, Linna Ge, Jens Michael Hertz, Clifford E. Kashtan, Yoshikazu Sado, Yoav Segal, Billy G. Hudson, Dorin-Bogdan Borza
Journal: Journal of the American Society of Nephrology (2013)

Alport post-transplant nephritis (APTN) is an aggressive form of anti-glomerular basement membrane disease that targets the allograft in transplanted patients with X-linked Alport syndrome. Alloantibodies develop against the NC1 domain of α5(IV) collagen, which occurs in normal kidneys, including renal allografts, forming distinct α345(IV) and α1256(IV) networks. Here, we studied the roles of these networks as antigens inciting alloimmunity and as targets of nephritogenic alloantibodies in APTN. We found that patients with APTN, but not those without nephritis, produce two kinds of alloantibodies against allogeneic collagen IV. Some alloantibodies targeted alloepitopes within α5NC1 monomers, shared by α345NC1 and α1256NC1 hexamers. Other alloantibodies specifically targeted alloepitopes that depended on the quaternary structure of α345NC1 hexamers. In Col4a5-null mice, immunization with native forms of allogeneic collagen IV exclusively elicited antibodies to quaternary α345NC1 alloepitopes, whereas alloimmunogens lacking native quaternary structure elicited antibodies to shared α5NC1 alloepitopes. These results imply that quaternary epitopes within α345NC1 hexamers may initiate alloimmune responses after transplant in X-linked Alport patients. Thus, α345NC1 hexamers are the culprit alloantigen and primary target of all alloantibodies mediating APTN, whereas α1256NC1 hexamers become secondary targets of anti-α5NC1 alloantibodies. Reliable detection of alloantibodies by immunoassays using α345NC1 hexamers may improve outcomes by facilitating early, accurate diagnosis.
Clinical Trial Substantiates the Predictive Value of <b> <i>O-6-Methylguanine-DNA Methyltransferase</i> </b> Promoter Methylation in Glioblastoma Patients Treated with Temozolomide
Authors: Monika E. Hegi, Annie-Claire Diserens, Sophie Godard, Pierre-Yves Dietrich, Luca Regli, Sandrine Ostermann, Philippe Otten, Guy Van Melle, Nicolas de Tribolet, Roger Stupp
Journal: Clinical Cancer Research (2004)

In the setting of a prospective clinical trial, we determined the predictive value of the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter for outcome in glioblastoma patients treated with the alkylating agent temozolomide. Expression of this excision repair enzyme has been associated with resistance to alkylating chemotherapy.The methylation status of MGMT in the tumor biopsies was evaluated in 38 patients undergoing resection for newly diagnosed glioblastoma and enrolled in a Phase II trial testing concomitant and adjuvant temozolomide and radiation. The epigenetic silencing of the MGMT gene was determined using methylation-specific PCR.Inactivation of the MGMT gene by promoter methylation was associated with longer survival (P = 0.0051; Log-rank test). At 18 months, survival was 62% (16 of 26) for patients testing positive for a methylated MGMT promoter but reached only 8% (1 of 12) in absence of methylation (P = 0.002; Fisher's exact test). In the presence of other clinically relevant factors, methylation of the MGMT promoter remains the only significant predictor (P = 0.017; Cox regression).This prospective clinical trial identifies MGMT-methylation status as an independent predictor for glioblastoma patients treated with a methylating agent. The association of the epigenetic inactivation of the DNA repair gene MGMT with better outcome in this homogenous cohort may have important implications for the design of future trials and supports efforts to deplete MGMT by O-6-benzylguanine, a noncytotoxic substrate of this enzyme.
Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy.
Authors: J B Hibbs, C Westenfelder, R Taintor, Z Vavrin, C Kablitz, R L Baranowski, J H Ward, R L Menlove, M P McMurry, J P Kushner
Journal: Journal of Clinical Investigation (1992)

An interferon-gamma, tumor necrosis factor, and interleukin-1-inducible, high-output pathway synthesizing nitric oxide (NO) from L-arginine was recently identified in rodents. High-dose interleukin-2 (IL-2) therapy is known to induce the same cytokines in patients with advanced cancer. Therefore, we examined renal cell carcinoma (RCC; n = 5) and malignant melanoma (MM; n = 7) patients for evidence of cytokine-inducible NO synthesis. Activity of this pathway was evaluated by measuring serum and urine nitrate (the stable degradation product of NO) during IL-2 therapy. IL-2 administration caused a striking increase in NO generation as reflected by serum nitrate levels (10- and 8-fold increase [P less than 0.001, P less than 0.003] for RCC and MM patients, respectively) and 24-h urinary nitrate excretion (6.5- and 9-fold increase [both P less than 0.001] for RCC and MM patients, respectively). IL-2-induced renal dysfunction made only a minor contribution to increased serum nitrate levels. Metabolic tracer studies using L-[guanidino-15N2]arginine demonstrated that the increased nitrate production was derived from a terminal guanidino nitrogen atom of L-arginine. Our results showing increased endogenous nitrate synthesis in patients receiving IL-2 demonstrate for the first time that a cytokine-inducible, high-output L-arginine/NO pathway exists in humans.
Five-Factor Model of Personality Disorder: A Proposal for DSM-V
Authors: Thomas A. Widiger, Stephanie N. Mullins-Sweatt
Journal: Annual Review of Clinical Psychology (2008)

The predominant dimensional model of general personality structure within psychology is the five-factor model (FFM). Research indicates that the personality disorders of the American Psychiatric Association's diagnostic manual can be understood as maladaptive variants of the domains and facets of the FFM. The current review provides a proposal for the classification of personality disorder from the perspective of the FFM. Discussed as well are implications and issues associated with an FFM of personality disorder, including the integration of a psychiatric nomenclature with general personality structure, the inclusion of a domain of openness to experience, the identification of problems in living associated with maladaptive personality traits, the setting of a diagnostic threshold, prototypal matching, feasibility, and clinical utility.
hapbin: An Efficient Program for Performing Haplotype-Based Scans for Positive Selection in Large Genomic Datasets: Fig. 1.
Authors: Colin A. Maclean, Neil P. Chue Hong, James G.D. Prendergast
Journal: Molecular Biology and Evolution (2015)

Understanding how the genome is shaped by selective processes forms an integral part of modern biology. However, as genomic datasets continue to grow larger it is becoming increasingly difficult to apply traditional statistics for detecting signatures of selection to these cohorts. There is therefore a pressing need for the development of the next generation of computational and analytical tools for detecting signatures of selection in large genomic datasets. Here, we present hapbin, an efficient multithreaded implementation of extended haplotype homzygosity-based statistics for detecting selection, which is up to 3,400 times faster than the current fastest implementations of these algorithms.
Liposome-Encapsulated Curcumin Suppresses Growth of Head and Neck Squamous Cell Carcinoma<i>In vitro</i>and in Xenografts through the Inhibition of Nuclear Factor κB by an AKT-Independent Pathway
Authors: Dorothy Wang, Mysore S. Veena, Kerry Stevenson, Christopher Tang, Baran Ho, Jeffrey D. Suh, Victor M. Duarte, Kym F. Faull, Kapil Mehta, Eri S. Srivatsan, Marilene B. Wang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The purpose of this study was to determine whether a liposomal formulation of curcumin would suppress the growth of head and neck squamous cell carcinoma (HNSCC) cell lines CAL27 and UM-SCC1 in vitro and in vivo. Experimental Design: HNSCC cell lines were treated with liposomal curcumin at different doses and assayed for in vitro growth suppression using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A reporter gene assay was done on cell lines to study the effect of liposomal curcumin on nuclear factor κB (NFκB) activation. Western blot analysis was done to determine the effect of curcumin on the expression of NFκB, phospho-IκBα, phospho-AKT (pAKT), phospho-S6 kinase, cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S. Xenograft mouse tumors were grown and treated with intravenous liposomal curcumin. After 5 weeks, tumors were harvested and weighed. Immunohistochemistry and Western blot analyses were used to study the effect of liposomal curcumin on the expression of NFκB and pAKT. Results: The addition of liposomal curcumin resulted in a dose-dependent growth suppression of both cell lines. Liposomal curcumin treatment suppressed the activation of NFκB without affecting the expression of pAKT or its downstream target phospho-S6 kinase. Expression of cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S were reduced, indicating the effect of curcumin on the NFκB pathway. Nude mice xenograft tumors were suppressed after 3.5 weeks of treatment with i.v. liposomal curcumin, and there was no demonstrable toxicity of liposomal curcumin upon autopsy. Immunohistochemistry and Western blot analysis on xenograft tumors showed the inhibition of NFκB without affecting the expression of pAKT. Conclusions: Liposomal curcumin suppresses HNSCC growth in vitro and in vivo. The results suggest that liposomal curcumin is a viable nontoxic therapeutic agent for HNSCC that may work via an AKT-independent pathway.
Gastrointestinal Function Regulation by Nitrergic Efferent Nerves
Authors: Noboru Toda, Arnold G. Herman
Journal: Pharmacological Reviews (2005)

Gastrointestinal (GI) smooth muscle responses to stimulation of the nonadrenergic noncholinergic inhibitory nerves have been suggested to be mediated by polypeptides, ATP, or another unidentified neurotransmitter. The discovery of nitric-oxide (NO) synthase inhibitors greatly contributed to our understanding of mechanisms involved in these responses, leading to the novel hypothesis that NO, an inorganic, gaseous molecule, acts as an inhibitory neurotransmitter. The nerves whose transmitter function depends on the NO release are called "nitrergic", and such nerves are recognized to play major roles in the control of smooth muscle tone and motility and of fluid secretion in the GI tract. Endothelium-derived relaxing factor, discovered by Furchgott and Zawadzki, has been identified to be NO that is biosynthesized from l-arginine by the constitutive NO synthase in endothelial cells and neurons. NO as a mediator or transmitter activates soluble guanylyl cyclase and produces cyclic GMP in smooth muscle cells, resulting in relaxation of the vasculature. On the other hand, NO-induced GI smooth muscle relaxation is mediated, not only by cyclic GMP directly or indirectly via hyperpolarization, but also by cyclic GMP-independent mechanisms. Numerous cotransmitters and cross talk of autonomic efferent nerves make the neural control of GI functions complicated. However, the findingsrelated to the nitrergic innervation may provide us a new way of understanding GI tract physiology and pathophysiology and might result in the development of new therapies of GI diseases. This review article covers the discovery of nitrergic nerves, their functional roles, and pathological implications in the GI tract.
2-(3-{1-Carboxy-5-[(6-[18F]Fluoro-Pyridine-3-Carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid, [18F]DCFPyL, a PSMA-Based PET Imaging Agent for Prostate Cancer
Authors: Ying Chen, Mrudula Pullambhatla, Catherine A. Foss, Youngjoo Byun, Sridhar Nimmagadda, Srinivasan Senthamizhchelvan, George Sgouros, Ronnie C. Mease, Martin G. Pomper
Journal: Clinical Cancer Research (2011)

We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [(18)F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen (PSMA). PSMA is upregulated in prostate cancer epithelia and in the neovasculature of most solid tumors.[(18)F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[(18)F]fluoronicotinic acid tetrafluorophenyl ester ([(18)F]F-Py-TFP) for introduction of (18)F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PSMA PC3 PIP and PSMA- PC3 flu xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0.DCFPyL displays a K(i) value of 1.1 ± 0.1 nmol/L for PSMA. [(18)F]DCFPyL was produced in radiochemical yields of 36%-53% (decay corrected) and specific radioactivities of 340-480 Ci/mmol (12.6-17.8 GBq/μmol, n = 3). In an immunocompromised mouse model [(18)F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PSMA+ PC3 PIP tumor, with a ratio of 358:1 of uptake within PSMA+ PC3 PIP to PSMA- PC3 flu tumor placed in the opposite flank. At or after 1 hour postinjection, minimal nontarget tissue uptake of [(18)F]DCFPyL was observed. The bladder wall is the dose-limiting organ.These data suggest [(18)F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues.