tbuckley/cabot-search huggingface dataset:
Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma
Authors: Robert H.I. Andtbacka, Howard L. Kaufman, Frances Collichio, Thomas Amatruda, Neil Senzer, Jason Chesney, Keith A. Delman, Lynn E. Spitler, Igor Puzanov, Sanjiv S. Agarwala, Mohammed Milhem, Lee Cranmer, Brendan Curti, Karl Lewis, Merrick Ross, Troy Guthrie, Gerald P. Linette, Gregory A. Daniels, Kevin Harrington, Mark R. Middleton, Wilson H. Miller, Jonathan S. Zager, Yining Ye, Bin Yao, Ai Li, Susan Doleman, Ari VanderWalde, Jennifer Gansert, Robert S. Coffin
Journal: Journal of Clinical Oncology (2015)

Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial.Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate.Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred.T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.
Efficacy of intravenous administration of anti-tuberculosis drugs in patients with multidrug-resistant tuberculosis
Authors: Svitlana Cherenko, Nataliia Lytvynenko
Journal: European Respiratory Journal (2013)

Background. The treatment of patients with multidrug-resistant tuberculosis (MDR-TB) is a major issue due to high level of morbidity and mortality. The way to improve the outcomes in patients with MDR-TB is using some anti-tuberculosis drugs (ATD) in intravenous route. The objectives of this study were to evaluate the efficacy of intravenous versus oral administration of some ATD in patients with MDR-TB and to compare the main cost of these two regimens.  Methods. In the randomized controlled open-label clinical trial 60 individuals with MDR-TB received chemotherapy regimens included not less than 5 effectiveness anti-tuberculosis drugs (to which sensitivity of MBT is kept). These regimens differed only in that the patients of the main group received ethambutol (25 mg/kg), levofloxacin (15 mg/kg) and PAS (150 mg/kg) intravenously; the patients of the control received the same drugs in the same doses via oral route. Results. In patients of main group sputum conversion achieved in 83.3% vs. 60.0% of control (p
Cellular Recognition during Neural Development
Authors: D I Gottlieb, L Glaser
Journal: Annual Review of Neuroscience (1980)

Roger Sperry's chemoaffinity hypothesis, elegantly summarized in the pre­ ceding quotation (Sperry 1965), is one of the central ideas of contemporary neurobiology. When Sperry first proposed the chemoaffinity hypothesis, the experimental evidence for it consisted entirely of behavioral and anatomical studies. The proposed identification tags were necessary to explain the way axons grow during the regeneration of altered nervous pathways; the hy­ pot hesis gained widespread support because it was extremely difficult to imagine other reasonable explanations for the anatomical and behavioral results. Experimental support for the chemoaffinity hypothesis could theoreti­ cally be of two distinct kinds. In the first, the nervous system is altered and the assembly of nerve circuits is observed and compared to that in normal animals. If chemical identification tags offer a parsimonious explanation for the observed patterns of growth and connections, then the theory gains support. More direct support must come from experiments of a second kind, which study actual molecular content, in order to test the proposition
Do Hospitals and Surgeons With Higher Coronary Artery Bypass Graft Surgery Volumes Still Have Lower Risk-Adjusted Mortality Rates?
Authors: Edward L. Hannan, Chuntao Wu, Thomas J. Ryan, Edward Bennett, Alfred T. Culliford, Jeffrey P. Gold, Alan Hartman, O. Wayne Isom, Robert H. Jones, Barbara McNeil, Eric A. Rose, Valavanur A. Subramanian
Journal: Circulation (2003)

Background— Studies that are the basis of recommended volume thresholds for CABG surgery are outdated and not reflective of recent advances in the field. This study examines both hospital and surgeon volume-mortality relations for CABG surgery through the use of a population-based clinical data set. Methods and Results— Data from New York’s clinical CABG surgery registry from 1997 to 1999 (total number of procedures, 57 150) were used to examine the individual and combined impact of annual hospital volume and annual surgeon volume on in-hospital mortality rates after adjusting for differences in severity of illness. Significantly lower risk-adjusted mortality rates occurred above all annual hospital volume thresholds between 200 and 800 and above all surgeon volume thresholds between 50 and 200. The number needed to treat (NNT) at higher-volume providers to avoid a death was minimized for a hospital threshold volume of 100 (NNT=50) and a surgeon threshold volume of 50 (NNT=118). The risk-adjusted mortality rate (RAMR) for patients undergoing surgery performed by surgeons with volumes of ≥125 in hospitals with volumes of ≥600 was 1.89%. The RAMR was significantly higher (2.67%) for patients undergoing surgery performed by surgeons with volumes of &lt;125 in hospitals with volumes of &lt;600. Conclusions— Higher-volume surgeons and hospitals continue to have lower risk-adjusted mortality rates, and patients undergoing surgery performed by higher-volume surgeons in higher-volume hospitals have the lowest mortality rates.
Nebulised budesonide using a novel device in patients with oral steroid-dependent asthma
Authors: Claus Vogelmeier, Peter Kardos, Thomas Hofmann, Sebastian Canisius, Gerhard Scheuch, Bernhard Muellinger, Karlheinz Nocker, Guenter Menz, Klaus F. Rabe
Journal: European Respiratory Journal (2014)

This phase 2/3 randomised, parallel-group, placebo-controlled trial investigated oral corticosteroid (OCS)-sparing efficacy, safety and tolerability of nebulised budesonide (Bud) administered with a novel computer-controlled, compressor-driven inhalation system (AKITA) as add-on therapy to Global Initiative for Asthma step 5. Patients (18–65 years) with OCS-dependent asthma were randomised (2:1:1:1) to receive 18-week, twice-daily, double-blind treatment with AKITA inhaled corticosteroid (AICS)-Bud 1 mg, AICS-Bud 0.5 mg, AICS-placebo or open-label Bud 1 mg administered by conventional nebuliser (CN-Bud). OCS doses were tapered until week 14. 199 patients started treatment. More AICS-Bud 1 mg (80.0%) than placebo-treated (62.5%) patients had daily OCS doses reduced ≥50%, with clinical stability to week 18 (one-sided p=0.02; treatment difference: 17.5% (95% CI 0.1–34.9%), two-sided p=0.04). Mean± sd forced expiratory volume in 1 s improved (from baseline to week 18) for AICS-Bud 1 mg (239±460 mL, p&lt;0.001) and AICS-Bud 0.5 mg (126±345 mL, p=0.01) but not placebo (93±419 mL, p=0.36) or CN-Bud (137±459 mL, p=0.18). Fewer AICS-Bud 1 mg-treated patients experienced asthma exacerbations (7.5%) compared with placebo (17.5%) or CN-Bud (22.5%). All treatments were well tolerated. Budesonide applied with AKITA allowed significant meaningful OCS reduction in OCS-dependent asthma patients while improving pulmonary function and maintaining exacerbation control.
Active smoking negatively affects recovery of patients hospitalized due to acute exacerbation of chronic obstructive pulmonary disease (COPD)
Authors: Andrea Schäfer, Noémi Eszes, Zsuzsanna Kováts, Veronika Müller
Journal: European Respiratory Journal (2011)

COPD is a progressive inflammatory airway disease most often caused by smoking. Significant proportion of COPD patients continues to smoke even in advanced stages, mainly as the result of severe tobacco dependence. COPD predisposes to depression making symptoms worse. Frequency and effects of active smoking and depression in patients hospitalized due to acute exacerbation of COPD is unknown.  One hundred patients admitted to the Department of Pulmonology Semmelweis University with the diagnosis of COPD acute exacerbation were analyzed (men: women = 46:54). Detailed history, Fagerstrom nicotine dependence test (FNDT) and Beck depression inventory scale were registered, expiratory CO was measured. Spirometry at admission and release, length of hospital stay and data on medications were collected.  Current smoker (S group, N=45) were compared to former (N=44) and never smoker (N=9) patients (non-S group). FNDT confirmed low dependence (3.9±0.4 points), Beck test results showed significantly higher scores for possible depression in S patients (S:12.7±1.3 vs. non-S: 9.4±1.0 p  Our results indicate that in patients hospitalized due to acute exacerbation of COPD treatment of smoking dependence is absolutely indicated as active smoking decreased improvement in health status and significantly increased hospital stay.
After GWAS: Searching for Genetic Risk for Schizophrenia and Bipolar Disorder
Authors: Elliot S. Gershon, Ney Alliey-Rodriguez, Chunyu Liu
Journal: American Journal of Psychiatry (2011)

Ten years ago it was widely expected that the genetic basis of common disease would be resolved by genome-wide association studies (GWAS), large-scale studies in which the entire genome is covered by genetic markers. However, the bulk of heritable variance remains unexplained. The authors consider several alternative research strategies. For instance, whereas it has been hypothesized that a common disease is associated primarily with common genetic variants, it is now plausible that multiple rare variants each have a potent effect on disease risk and that they could accumulate to become a substantial component of common disease risk. This idea has become more appealing since the discovery that copy number variants (CNVs) are a substantial source of human mutations and are associated with multiple common diseases. CNVs are structural genomic variants consisting of microinsertions, microdeletions, and transpositions in the human genome. It has been argued that numerous rare CNVs are plausible causes of a substantial proportion of common disease, and rare CNVs have been found to be potent risk factors in schizophrenia and autism. Another approach is to "parse the genome," i.e., reanalyze subsets of current GWAS data, since the noise inherent in genome-wide approaches may be hiding valid associations. Lastly, technological advances and declining costs may allow large-scale genome-wide sequencing that would comprehensively identify all genetic variants. Study groups even larger than the 10,000 subjects in current meta-analyses would be required, but the outcomes may lead to resolution of our current dilemma in common diseases: Where is the missing heritability?
Increase in Expression of Adhesion Molecule Receptors on T Helper Cells During Antipsychotic Treatment and Relationship to Blood-Brain Barrier Permeability in Schizophrenia
Authors: Norbert Mï¿½ller, Michael Riedel, Myriam Hadjamu, Markus J. Schwarz, Manfred Ackenheil, Rudolf Gruber
Journal: American Journal of Psychiatry (1999)

The authors estimated the expression of adhesion molecule receptors (VLA-4 and LFA-1) on T helper (CD4+) and T suppressor/cytotoxic (CD8+) lymphocytes in schizophrenic patients before and during antipsychotic treatment and studied the relationship of these subpopulations to CSF measures and blood-brain barrier permeability.Blood was drawn from hospitalized patients with schizophrenia before (N = 45) and after (N = 22) neuroleptic treatment and from an age-matched comparison group (N = 41). Lumbar punctures were performed on 32 of the schizophrenic patients.During antipsychotic treatment there were significant increases in the percentage of VLA-4+/CD4+ and VLA-4+/CD8+ cells. VLA-4+/CD4+ and LFA-1+/CD4+ cells were both closely related to disturbance of the blood-brain barrier. Higher values for VLA-4+/CD4+ and LFA-1+/CD4+ cells were found in patients with a disturbed blood-brain barrier.The findings suggest that adhesion molecules are involved in immunoregulation between the central nervous system and the peripheral immune system in schizophrenia.
A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains
Authors: Michelle M Simon, Simon Greenaway, Jacqueline K White, Helmut Fuchs, Valérie Gailus-Durner, Sara Wells, Tania Sorg, Kim Wong, Elodie Bedu, Elizabeth J Cartwright, Romain Dacquin, Sophia Djebali, Jeanne Estabel, Jochen Graw, Neil J Ingham, Ian J Jackson, Andreas Lengeling, Silvia Mandillo, Jacqueline Marvel, Hamid Meziane, Frédéric Preitner, Oliver Puk, Michel Roux, David J Adams, Sarah Atkins, Abdel Ayadi, Lore Becker, Andrew Blake, Debra Brooker, Heather Cater, Marie-France Champy, Roy Combe, Petr Danecek, Armida di Fenza, Hilary Gates, Anna-Karin Gerdin, Elisabetta Golini, John M Hancock, Wolfgang Hans, Sabine M Hölter, Tertius Hough, Pierre Jurdic, Thomas M Keane, Hugh Morgan, Werner Müller, Frauke Neff, George Nicholson, Bastian Pasche, Laura-Anne Roberson, Jan Rozman, Mark Sanderson, Luis Santos, Mohammed Selloum, Carl Shannon, Anne Southwell, Glauco P Tocchini-Valentini, Valerie E Vancollie, Henrik Westerberg, Wolfgang Wurst, Min Zi, Binnaz Yalcin, Ramiro Ramirez-Solis, Karen P Steel, Ann-Marie Mallon, Martin Hrabě de Angelis, Yann Herault, Steve DM Brown
Journal: Genome biology (2013)

The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms.We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems.Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.
Nucleic Acid Biotechnology
Authors: Charles M. Roth, Martin L. Yarmush
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Driven by advances in the acquisition of genetic sequence information and the ability to manipulate small quantities of nucleic acid, a number of technologies are emerging that exploit nucleic acids for research, diagnostic, and therapeutic utility. In this review, we cover three technologies based on nucleic acids—DNA microarrays, antisense technology, and gene therapy—that are especially promising and may make a substantial impact in the laboratory and in the clinic during the coming years. For each of these areas, an overview of the current status and applications is provided, followed by a discussion of critical issues and challenges to be faced for further advancement of the technology; an emphasis is placed on quantitative and engineering aspects.
Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia
Authors: Séverine Loisel, Pierre-Alain André, Josee Golay, Franz Buchegger, Jean Kadouche, Martine Cérutti, Luca Bologna, Marek Kosinski, David Viertl, Angelika Bischof Delaloye, Christian Berthou, Jean-Pierre Mach, Laurence Boumsell
Journal: Molecular Cancer (2011)

Abstract Background The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment. To this aim, we analyse the biological and therapeutic properties of three mAbs directed against the CD5, CD71 or HLA-DR molecules highly expressed on B-CLL cells. Results The three mAbs, after purification and radiolabelling demonstrated high and specific binding capacity to various human leukaemia target cells. Further in vitro analysis showed that mAb anti-CD5 induced neither growth inhibition nor apoptosis, mAb anti-CD71 induced proliferation inhibition with no early sign of cell death and mAb anti-HLA-DR induced specific cell aggregation, but without evidence of apoptosis. All three mAbs induced various degrees of ADCC by NK cells, as well as phagocytosis by macrophages. Only the anti-HLA-DR mAb induced complement mediated lysis. Coincubation of different pairs of mAbs did not significantly modify the in vitro results. In contrast with these discrete and heterogeneous in vitro effects, in vivo the three mAbs demonstrated marked anti-tumour efficacy and prolongation of mice survival in two models of SCID mice, grafted either intraperitoneally or intravenously with the CD5 transfected JOK1-5.3 cells. This cell line was derived from a human hairy cell leukaemia, a type of malignancy known to have very similar biological properties as the B-CLL, whose cells constitutively express CD5. Interestingly, the combined injection of anti-CD5 with anti-HLA-DR or with anti-CD71 led to longer mouse survival, as compared to single mAb injection, up to complete inhibition of tumour growth in 100% mice treated with both anti-HLA-DR and anti-CD5. Conclusions Altogether these data suggest that the combined use of two mAbs, such as anti-HLA-DR and anti-CD5, may significantly enhance their therapeutic potential.
Molecular Portraits and 70-Gene Prognosis Signature Are Preserved throughout the Metastatic Process of Breast Cancer
Authors: Britta Weigelt, Zhiyuan Hu, Xiaping He, Chad Livasy, Lisa A. Carey, Matthew G. Ewend, Annuska M. Glas, Charles M. Perou, Laura J. van't Veer
Journal: Cancer Research (2005)

Abstract Microarray analysis has been shown to improve risk stratification of breast cancer. Breast tumors analyzed by hierarchical clustering of expression patterns of “intrinsic” genes have been reported to subdivide into at least four molecular subtypes that are associated with distinct patient outcomes. Using a supervised method, a 70-gene expression profile has been identified that predicts the later appearance or absence of clinical metastasis in young breast cancer patients. Here, we show that distant metastases display both the same molecular breast cancer subtype as well as the 70-gene prognosis signature as their primary tumors. Our results suggest that the capacity to metastasize is an inherent feature of most breast cancers. Furthermore, our data imply that poor prognosis breast carcinomas classified either by the intrinsic gene set or the 70 prognosis genes represent distinct disease entities that seem sustained throughout the metastatic process.
Advances in the science of objective physical activity monitoring: 3rd International Conference on Ambulatory Monitoring of Physical Activity and Movement
Authors: Stewart G Trost, Catrine Tudor-Locke
Journal: British Journal of Sports Medicine (2014)

This theme issue of BJSM presents key papers from the 3rd International Conference on Ambulatory Monitoring of Physical Activity and Movement (ICAMPAM). The July 2013 conference was hosted by the University of Massachusetts and was attended by researchers, clinicians, students and technology vendors for North America, Europe, Australasia and Asia.

Delegates from a wide range of academic disciplines and professions, including sports medicine, computer science and engineering, statistics, exercise science, rehabilitation science, and health promotion presented symposia and papers addressing five broad conference themes: (1) behaviour and health outcomes; (2) data processing, statistics and computation science; (3) validation and calibration; (4) engineering and tool development and (5) clinical applications.

ICAMPAM was a truly unique scientific meeting in that it provided an international forum for the dissemination of cutting edge multidisciplinary research related to the measurement of physical activity and sedentary behaviours in daily life. While the focus of the conference was primarily methodological, the resultant advances in measurement technology have immediate and positive impacts on clinical and public …
Myositis ossificans traumatica. Association with hemophilia (factor XI deficiency) in a football player
Authors: P. Joki
Journal: JAMA (1977)

A case report of an outstanding college football halfback with partial factor XI deficiency, recurrent ecchymosis, and myositis ossificans is reviewed. The association of multiple areas of myositis ossificans and partial clotting-factor deficiency has not been noted in the past. The importance of considering this diagnosis in participants in contact sports with the above findings is emphasized. (<i>JAMA</i>237:2215-2216, 1977)