tbuckley/cabot-search huggingface dataset:
Coexistence of Staphylococcal Scalded Skin Syndrome and Acute Graft-vs-Host Disease
Authors: Cristina Thomas, Pedram Yazdan, Jonathan A. Cotliar
Journal: JAMA Dermatology (2014)

cantly (McNemar test, P < .05for all), but these gains were highest for discussions with siblings and children.For example, intended discussion with brothers increased to 73% from 42% reported at baseline.Discussion | Genetic testing for melanoma risk presents multiple opportunities for family risk awareness and prevention. 6 Findings indicate that FDRs of patients with melanoma are likely to talk with a range of family members about melanoma risk and that positive risk feedback (high-risk mutation, gene environment, and nongenetic) increases intended discussions more than negative feedback.Increased communication with siblings and children, in particular, may be a worthwhile outcome of melanoma genetic testing.Specific guidance on the importance of family communication and risk reduction may be particularly important in the provision of negative genetic testing information.
The Globin Gene Repertoire of Lampreys: Convergent Evolution of Hemoglobin and Myoglobin in Jawed and Jawless Vertebrates
Authors: Kim Schwarze, Kevin L. Campbell, Thomas Hankeln, Jay F. Storz, Federico G. Hoffmann, Thorsten Burmester
Journal: Molecular Biology and Evolution (2014)

Agnathans (jawless vertebrates) occupy a key phylogenetic position for illuminating the evolution of vertebrate anatomy and physiology. Evaluation of the agnathan globin gene repertoire can thus aid efforts to reconstruct the origin and evolution of the globin genes of vertebrates, a superfamily that includes the well-known model proteins hemoglobin and myoglobin. Here, we report a comprehensive analysis of the genome of the sea lamprey (Petromyzon marinus) which revealed 23 intact globin genes and two hemoglobin pseudogenes. Analyses of the genome of the Arctic lamprey (Lethenteron camtschaticum) identified 18 full length and five partial globin gene sequences. The majority of the globin genes in both lamprey species correspond to the known agnathan hemoglobins. Both genomes harbor two copies of globin X, an ancient globin gene that has a broad phylogenetic distribution in the animal kingdom. Surprisingly, we found no evidence for an ortholog of neuroglobin in the lamprey genomes. Expression and phylogenetic analyses identified an ortholog of cytoglobin in the lampreys; in fact, our results indicate that cytoglobin is the only orthologous vertebrate-specific globin that has been retained in both gnathostomes and agnathans. Notably, we also found two globins that are highly expressed in the heart of P. marinus, thus representing functional myoglobins. Both genes have orthologs in L. camtschaticum. Phylogenetic analyses indicate that these heart-expressed globins are not orthologous to the myoglobins of jawed vertebrates (Gnathostomata), but originated independently within the agnathans. The agnathan myoglobin and hemoglobin proteins form a monophyletic group to the exclusion of functionally analogous myoglobins and hemoglobins of gnathostomes, indicating that specialized respiratory proteins for O2 transport in the blood and O2 storage in the striated muscles evolved independently in both lineages. This dual convergence of O2-transport and O2-storage proteins in agnathans and gnathostomes involved the convergent co-option of different precursor proteins in the ancestral globin repertoire of vertebrates.
S-nitroso human serum albumin reduces ischaemia/reperfusion injury in the pig heart after unprotected warm ischaemia
Authors: S. Hallstrom, M. Franz, H. Gasser, M. Vodrazka, S. Semsroth, U. M. Losert, M. Haisjackl, B. K. Podesser, T. Malinski
Journal: Cardiovascular Research (2007)

Uncoupled endothelial nitric oxide synthase (eNOS) is a major contributor to vascular reactive oxygen species generation in ischaemia/reperfusion (I/R) injury. Supplementation of NO by the novel NO donor S-nitroso human serum albumin (S-NO-HSA) may inhibit uncoupling of eNOS (feedback inhibition).Pigs (n = 14; 33.1 +/- 1.7 kg) were continuously monitored for heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and coronary flow (CF). Infusion of either human serum albumin (n = 8; controls) or S-NO-HSA (n = 6) lasted 60 min (0.1 micromol/kg/h) starting 15 min prior to ischaemia. After clamping the aorta under cardiopulmonary bypass (CPB), the hearts underwent 15 min of warm, unprotected ischaemia (37 degrees C). Reperfusion lasted 150 min (30 min under CPB; 15 min weaning; additional 105 min reperfusion). In biopsies from non-ischaemic hearts and myocardial biopsies taken after 150 min of reperfusion, high-energy phosphates were measured and the calcium ionophore-stimulated release of NO, superoxide, and peroxynitrite (ONOO(-)) were monitored with nanosensors. Compared with non-ischaemic hearts, the NO level decreased from 930 +/- 25 to 600 +/- 15 nmol/L (P < 0.001) while the superoxide level increased from 45 +/- 5 to 110 +/- 10 nmol/L (P < 0.001) after ischaemia. S-NO-HSA restored the NO level to 825 +/- 20 nmol/L, shifted favourably the [NO]/[ONOO(-)] balance (a marker of eNOS uncoupling) from 1.36 +/- 0.06 (ischaemia) to 3.59 +/- 0.18, significantly improved CF (65 +/- 10 vs. control, 43 +/- 5 mL/min, P < 0.05), MAP (57 +/- 5 vs. 39 +/- 3 mm Hg, P < 0.01), LVSP (106 +/- 5 vs. 81 +/- 4 mm Hg, P < 0.01) and phosphocreatine (PCr) content (41.5 +/- 7.3 vs. 18.0 +/- 5.6 micromol/g protein; P < 0.01) at 150 min of reperfusion.Long-lasting release of NO by S-NO-HSA prevented uncoupling of eNOS and thereby improved systolic and diastolic function, myocardial perfusion, and the energetic reserve of the heart after I/R injury.
Letter to the editor: Measles on the cruise ship: links with virus spreading into an emergency department in Southern Italy
Authors: V Cozza, M Chironna, C Leo, R Prato
Journal: Eurosurveillance (2014)

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TAXUS III Trial
Authors: Kengo Tanabe, Patrick W. Serruys, Eberhard Grube, Pieter C. Smits, Guido Selbach, Willem J. van der Giessen, Manfred Staberock, Pim de Feyter, Ralf Müller, Evelyn Regar, Muzaffer Degertekin, Jurgen M.R. Ligthart, Clemens Disco, Bianca Backx, Mary E. Russell
Journal: Circulation (2003)

The first clinical study of paclitaxel-eluting stent for de novo lesions showed promising results. We performed the TAXUS III trial to evaluate the feasibility and safety of paclitaxel-eluting stent for the treatment of in-stent restenosis (ISR).The TAXUS III trial was a single-arm, 2-center study that enrolled 28 patients with ISR meeting the criteria of lesion length < or =30 mm, 50% to 99% diameter stenosis, and vessel diameter 3.0 to 3.5 mm. They were treated with one or more TAXUS NIRx paclitaxel-eluting stents. Twenty-five patients completed the angiographic follow-up at 6 months, and 17 of these underwent intravascular ultrasound (IVUS) examination. No subacute stent thrombosis occurred up to 12 months, but there was one late chronic total occlusion, and additional 3 patients showed angiographic restenosis. The mean late loss was 0.54 mm, with neointimal hyperplasia volume of 20.3 mm3. The major adverse cardiac event rate was 29% (8 patients; 1 non-Q-wave myocardial infarction, 1 coronary artery bypass grafting, and 6 target lesion revascularization [TLR]). Of the patients with TLR, 1 had restenosis in a bare stent implanted for edge dissection and 2 had restenosis in a gap between 2 paclitaxel-eluting stents. Two patients without angiographic restenosis underwent TLR as a result of the IVUS assessment at follow-up (1 incomplete apposition and 1 insufficient expansion of the stent).Paclitaxel-eluting stent implantation is considered safe and potentially efficacious in the treatment of ISR. IVUS guidance to ensure good stent deployment with complete coverage of target lesion may reduce reintervention.
Preclinical Characterization of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway
Authors: Adrian von Witzleben, Lukas T. Goerttler, Ralf Marienfeld, Holger Barth, André Lechel, Kevin Mellert, Michael Böhm, Marko Kornmann, Regine Mayer-Steinacker, Alexandra von Baer, Markus Schultheiss, Adrienne M. Flanagan, Peter Möller, Silke Brüderlein, Thomas F.E. Barth
Journal: Cancer Research (2015)

Abstract Chordomas are tumors that arise at vertebral bodies and the base of the skull. Although rare in incidence, they are deadly owing to slow growth and a lack of effective therapeutic options. In this study, we addressed the need for chordoma cell systems that can be used to identify therapeutic targets and empower testing of candidate pharmacologic drugs. Eight human chordoma cell lines that we established exhibited cytology, genomics, mRNA, and protein profiles that were characteristic of primary chordomas. Candidate responder profiles were identified through an immunohistochemical analysis of a chordoma tissue bank of 43 patients. Genomic, mRNA, and protein expression analyses confirmed that the new cell systems were highly representative of chordoma tissues. Notably, all cells exhibited a loss of CDKN2A and p16, resulting in universal activation of the CDK4/6 and Rb pathways. Therefore, we investigated the CDK4/6 pathway and responses to the CDK4/6–specific inhibitor palbociclib. In the newly validated system, palbociclib treatment efficiently inhibited tumor cell growth in vitro and a drug responder versus nonresponder molecular signature was defined on the basis of immunohistochemical expression of CDK4/6/pRb (S780). Overall, our work offers a valuable new tool for chordoma studies including the development of novel biomarkers and molecular targeting strategies. Cancer Res; 75(18); 3823–31. ©2015 AACR.
A Consistent Phylogenetic Backbone for the Fungi
Authors: I. Ebersberger, R. de Matos Simoes, A. Kupczok, M. Gube, E. Kothe, K. Voigt, A. von Haeseler
Journal: Molecular Biology and Evolution (2011)

The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data—a common practice in phylogenomic analyses—introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses.
Dermoscopy of circumscribed juvenile pityriasis rubra pilaris
Authors: Alicia López-Gómez, Ángel Vera-Casaño, Elisabeth Gómez-Moyano, Tania Salas-García, María Dorado-Fernández, Jesús Hernández-Gil-Sánchez, Antonio Ramírez-Andreo, Andrés Sanz-Trelles
Journal: Journal of the American Academy of Dermatology (2014)
Effectiveness of smoking cessation in patients with psychiatric disease
Authors: Zeynep Pinar Önen, Elif Sen, Banu Eris Gülbay, Pinar Akin Kabalak, Öznur Akkoca Yildiz, Turan Acican, Sevgi Saryal, Gülseren Karabiyikoglu
Journal: European Respiratory Journal (2012)

Background: Smoking cessation treatment is considered to be less effective in patients with psychiatric diseases.  Aim: To evaluate the smoking cessation rate in patients with psychiatric diseases, compare the effectiveness between the different treatment modalities and demonstrate the discrepancies from other patients.  Methods: From a total number of 609 active smokers; 52 with psychiatric diseases (most distinctive concomitant condition was depression) were prospectively evaluated between 2004 and 2010. Each patient answers the same questionnaire including smoking status and medical background. Nicotine dependence and CO levels were evaluated. Smoking cessation program was administered individually according to the guidelines and all of the patients were followed at least l year.  Results: There was no difference between the groups in; age, baseline Fagerstrom nicotine addiction score, exhaled carbon monoxide level and treatment protocols. However, total amount of smoked tobacco (27,8±21pack-year) and cigarette consumption per day (21±10) was higher in patients with psychiatric diseases (p=0.001 for all). The cessation rates with or without psychiatric diseases are respectively 44,2% and 55,6%. Effectiveness of treatment modalities are 44,4% for nicotine replacement treatment (NRT), 75% for bupropion, 25% for varenicline and 33,3% for behavioral treatment without pharmacotherapy in psychiatric diseases.  Conclusion: According to our results, one year smoking cessation success was lower in psychiatric diseases. Pharmacotherapy is superior to pure behavioral treatment. Bupropion and varenicline seems to more effective than NRT at relapse rates.
AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update
Authors: Thomas A. Pearson, Steven N. Blair, Stephen R. Daniels, Robert H. Eckel, Joan M. Fair, Stephen P. Fortmann, Barry A. Franklin, Larry B. Goldstein, Philip Greenland, Scott M. Grundy, Yuling Hong, Nancy Houston Miller, Ronald M. Lauer, Ira S. Ockene, Ralph L. Sacco, James F. Sallis, Sidney C. Smith, Neil J. Stone, Kathryn A. Taubert
Journal: Circulation (2002)

HomeCirculationVol. 106, No. 3AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update
Preoperative Twice-Weekly Paclitaxel With Concurrent Radiation Therapy Followed by Surgery and Postoperative Doxorubicin-Based Chemotherapy in Locally Advanced Breast Cancer: A Phase I/II Trial
Authors: Silvia C. Formenti, Matthew Volm, Kristin A. Skinner, Darcy Spicer, Deidre Cohen, Edith Perez, Anna C. Bettini, Susan Groshen, Conway Gee, Barbara Florentine, Michael Press, Peter Danenberg, Franco Muggia
Journal: Journal of Clinical Oncology (2003)

Preoperative chemotherapy is the conventional primary treatment in locally advanced breast cancer (LABC). We investigated the safety and efficacy of primary twice-weekly paclitaxel and concurrent radiation (RT) before modified radical mastectomy followed by adjuvant doxorubicin-based chemotherapy.Stage IIB (T3N0) to III LABC patients were eligible. Primary chemoradiation consisted of paclitaxel, 30 mg/m(2) delivered intravenously for 1 hour twice weekly for a total of 8 to 10 weeks, and concurrent RT (45 Gy at 1.8 Gy/fraction). Modified radical mastectomy was performed at least 2 weeks after completion of chemoradiation or on recovery of skin toxicity. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan.Forty-four patients were accrued. Toxicity from paclitaxel/RT included grade 3 skin desquamation (7%), hypersensitivity (2%), and stomatitis (2%). Postsurgery complications occurred in six patients (14%). The only grade 4 toxicity of postmastectomy chemotherapy was hematologic (10%). Grade 3 toxicities were leukopenia (24%), infection (22%), peripheral neuropathy (17%), arthralgia and pain (17%), stomatitis (12%), fatigue (10%), esophagitis (5%), and nausea (2%). Overall clinical response rate to preoperative paclitaxel and RT was 91%. Thirty-four percent of patients achieved a pathologic response in the mastectomy specimen: 16% pathologic complete responses (clearance of invasive cancer in the breast and axillary contents) and 18% pathologic partial responses (< 10 residual microscopic foci of invasive breast cancer).Twice-weekly paclitaxel with concurrent RT is a feasible and effective primary treatment for LABC. Future studies should compare primary chemoradiation to chemotherapy in LABC.
Recombinant Adeno-Associated Virus 2-Mediated Antiangiogenic Prevention in a Mouse Model of Intraperitoneal Ovarian Cancer
Authors: Tatyana Isayeva, Changchun Ren, Selvarangan Ponnazhagan
Journal: Clinical Cancer Research (2005)

In the present study, we sought to determine the potential of sustained transgene expression by a single i.m. administration of recombinant adeno-associated virus 2 (rAAV) encoding angiostatin and endostatin in inhibiting i.p. ovarian cancer growth and dissemination in a preclinical mouse model.Cohorts of female athymic nude mice received either no virus or 1.2 x 10(11) particles of rAAV encoding green fluorescence protein or endostatin plus angiostatin, i.m. Three weeks later, the mice were i.p. injected with 10(6) human epithelial ovarian cancer cell line SKOV3.ip1. As a measure of effectiveness of the therapy, tumor weight, abdominal distension, ascites volume and vascular endothelial growth factor level, and tumor weight were determined. Immunohistochemistry was done to determine tumor cell apoptosis and endothelial cell proliferation following the therapy. Tumor-free survival was recorded as the end point.Results indicated a significant tumor-free survival (P < 0.003) following therapy with rAAV encoding endostatin and angiostatin compared with untreated or rAAV-green fluorescence protein-treated mice. Ascites volume in rAAV endostatin and angiostatin-treated mice was significantly lower than naive mice and contained less hemorrhage and tumor conglomerates. The level of vascular endothelial growth factor in the ascites of antiangiogenic vector treated mice was also significantly less compared with the untreated mice. Immunohistochemical analyses indicated increased tumor cell apoptosis and decreased blood vasculature following rAAV endostatin and angiostatin treatment.The results indicate that antiangiogenic genetic prevention from stable systemic levels of angiostatin and endostatin by i.m. administration of rAAV can be used for the treatment of i.p. ovarian cancer growth and dissemination.
Cardiovascular Effects of Griseofulvin
Authors: EARL E. ALDINGER
Journal: Circulation Research (1968)

The intravenous administration of griseofulvin in doses of 3.0 mg/kg to 32 anesthetized open-chest dogs produced marked increments (43%) in isometric systolic force measured by a strain gauge. These changes were accompanied by an increase (22%) in heart rate and a decrease (25%) in blood pressure. The effect was unaltered by clamping the blood supply to and from the adrenal glands or by previous treatment with 1 mg/kg reserpine, 0.4 mg/kg propranolol HCl, 10 mg/kg hexamethonium chloride, 1 mg/kg phentolamine HCl or 2 mg/kg atropine. In 11 anesthetized open-chest rats and 7 isolated rabbit hearts, griseofulvin also increased the force of contraction. It may be inferred from these experiments that griseofulvin has a direct action on the cardiovascular system rather than one mediated through neurogenic or hormonal mechanisms. These cardiovascular changes may occur in patients in whom griseofulvin is used in the treatment of fungus diseases.
Effect of Statin Use During Hospitalization for Intracerebral Hemorrhage on Mortality and Discharge Disposition
Authors: Alexander C. Flint, Carol Conell, Vivek A. Rao, Jeff G. Klingman, Stephen Sidney, S. Claiborne Johnston, J. Claude Hemphill, Hooman Kamel, Stephen M. Davis, Geoffrey A. Donnan
Journal: JAMA Neurology (2014)

Statin use during hospitalization is associated with improved survival and a better discharge disposition among patients with ischemic stroke. It is unclear whether inpatient statin use has a similar effect among patients with intracerebral hemorrhage (ICH).To determine whether inpatient statin use in ICH is associated with improved outcomes and whether the cessation of statin use is associated with worsened outcomes.Retrospective cohort study of 3481 patients with ICH admitted to any of 20 hospitals in a large integrated health care delivery system over a 10-year period. Detailed electronic medical and pharmacy records were analyzed to explore the association between inpatient statin use and outcomes.The primary outcome measures were survival to 30 days after ICH and discharge to home or inpatient rehabilitation facility. We used multivariable logistic regression, controlling for demographics, comorbidities, initial severity, and code status. In addition, we used instrumental variable modeling to control for confounding by unmeasured covariates at the individual patient level.Among patients hospitalized for ICH, inpatient statin users were more likely than nonusers to be alive 30 days after ICH (odds ratio [OR], 4.25 [95% CI, 3.46-5.23]; P < .001) and were more likely than nonusers to be discharged to their home or an acute rehabilitation facility (OR, 2.57 [95% CI, 2.16-3.06]; P < .001). Patients whose statin therapy was discontinued were less likely than statin users to survive to 30 days (OR, 0.16 [95% CI, 0.12-0.21]; P < .001) and were less likely than statin users to be discharged to their home or an acute rehabilitation facility (OR, 0.26 [95% CI, 0.20-0.35]; P < .001). Instrumental variable models of local treatment environment (to control for confounding by unmeasured covariates) confirmed that a higher probability of statin therapy was associated with a higher probability of 30-day survival (with an increase in probability of 0.15 [95% CI, 0.04-0.25]; P = .01) and a better chance of being discharged to home or an acute rehabilitation facility (with an increase in probability of 0.13 [95% CI, 0.02-0.24]; P = .02).Inpatient statin use is associated with improved outcomes after ICH, and the cessation of statin use is associated with worsened outcomes after ICH. Given the association between statin cessation and substantially worsened outcomes, the risk-benefit balance of discontinuing statin therapy in the acute setting of ICH should be carefully considered.