tbuckley/cabot-search huggingface dataset:
Mantle Cell Lymphoma International Prognostic Index but Not Pretransplantation Induction Regimen Predicts Survival for Patients With Mantle-Cell Lymphoma Receiving High-Dose Therapy and Autologous Stem-Cell Transplantation
Authors: Lihua E. Budde, Katherine A. Guthrie, Brian G. Till, Oliver W. Press, Thomas R. Chauncey, John M. Pagel, Steven H. Petersdorf, William I. Bensinger, Leona A. Holmberg, Andrei R. Shustov, Damian J. Green, David G. Maloney, Ajay K. Gopal
Journal: Journal of Clinical Oncology (2011)

Purpose High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) are frequently used in an attempt to improve outcome in patients with mantle-cell lymphoma (MCL); however, the importance of intensive induction regimens before transplantation is unknown. Patients and Methods To address this question, we evaluated baseline characteristics, time to treatment, induction regimen, disease status at the time of transplantation, and MIPI score at diagnosis and their associations with survival in 118 consecutive patients with MCL who received HDT and ASCT at our centers. Results The MIPI was independently associated with survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P &lt; .001) and in the 85 patients who underwent ASCT as initial consolidation (HR, 7.2; P &lt; .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively. Low-risk MIPI scores were more common in the intensive induction group than the standard induction group in all patients (64% v 46%, respectively; P = .03) and in the initial consolidation group (66% v 45%, respectively; P = .03). After adjustment for the MIPI, an intensive induction regimen was not associated with improved survival after transplantation in all patients (HR, 0.5; P = .10), the initial consolidation group (HR, 1.1; P = .86), or patients ≤ 60 years old (HR, 0.6; P = .50). Observation of more than 3 months before initiating therapy did not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in patients receiving ASCT. Conclusion An intensive induction regimen before HDT and ASCT was not associated with improved survival after adjusting for differences in MIPI scores at diagnosis.
Synonymous and Nonsynonymous Polymorphisms versus Divergences in Bacterial Genomes
Authors: A. L. Hughes, R. Friedman, P. Rivailler, J. O. French
Journal: Molecular Biology and Evolution (2008)

Comparison of the ratio of nonsynonymous to synonymous polymorphisms within species with the ratio of nonsynonymous to synonymous substitutions between species has been widely used as a supposed indicator of positive Darwinian selection, with the ratio of these 2 ratios being designated as a neutrality index (NI). Comparison of genome-wide polymorphism within 12 species of bacteria with divergence from an outgroup species showed substantial differences in NI among taxa. A low level of nonsynonymous polymorphism at a locus was the best predictor of NI < 1, rather than a high level of nonsynonymous substitution between species. Moreover, genes with NI < 1 showed a strong tendency toward the occurrence of rare nonsynonymous polymorphisms, as expected under the action of ongoing purifying selection. Thus, our results are more consistent with the hypothesis that a high relative rate of between-species nonsynonymous substitution reflects mainly the action of purifying selection within species to eliminate slightly deleterious mutations rather than positive selection between species. This conclusion is consistent with previous results highlighting an important role of slightly deleterious variants in bacterial evolution and suggests caution in the use of the McDonald–Kreitman test and related statistics as tests of positive selection.
Bioactive androgens and glucuronidated androgen metabolites are associated with subcutaneous and ectopic skeletal muscle adiposity among older black men
Authors: Iva Miljkovic, Jane A. Cauley, Amy S. Dressen, Christopher L. Gordon, Bret H. Goodpaster, Lewis H. Kuller, Clareann H. Bunker, Alan L. Patrick, Victor W. Wheeler, Eric S. Orwoll, Joseph M. Zmuda
Journal: Metabolism (2011)
Ultrasound Imaging–Guided Noninvasive Ultrasound Thrombolysis
Authors: Uri Rosenschein, Vladimir Furman, Efim Kerner, Itzchak Fabian, Joelle Bernheim, Yoram Eshel
Journal: Circulation (2000)

Background —Catheter-based therapeutic ultrasound thrombolysis was recently shown to be effective and safe. The purpose of this work was to study the safety and efficacy of external high-intensity focused ultrasound thrombolysis guided by ultrasound imaging in experimental settings. Methods and Results —A therapeutic transducer was constructed from an acoustic lens and integrated with an ultrasound imaging transducer. In vitro clots were inserted into bovine arterial segments and sonicated under real-time ultrasound imaging guidance in a water tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with thrombolysis efficiency ( r 2 =0.7666). A thrombolysis efficiency of 91% was achieved with optimal PW parameters (1:25 duty cycle, 200-μs pulse length) at an intensity (I spta ) of &gt;35±5 W/cm 2 . Ultrasound imaging during sonication showed the cavitation field as a spherical cloud of echo-dense material. Within &lt;2 minutes, the vessel lumen evidenced neither residual clot nor damage to the arterial wall. On serial filtration, 93±1% of the lysed clot became subcapillary in size (&lt;8 μm). In vitro safety studies, however, showed arterial damage when an I spta of 45 W/cm 2 was used for periods of ≥300 seconds. Conclusions —External high-intensity focused ultrasound thrombolysis using optimal PW parameters for periods of ≤300 seconds appears to be a safe and effective method to induce thrombolysis. The procedure can be guided by ultrasound imaging, thereby allowing the monitoring of therapy.
Median-joining networks for inferring intraspecific phylogenies
Authors: H. J. Bandelt, P. Forster, A. Rohl
Journal: Molecular Biology and Evolution (1999)

Reconstructing phylogenies from intraspecific data (such as human mitochondrial DNA variation) is often a challenging task because of large sample sizes and small genetic distances between individuals. The resulting multitude of plausible trees is best expressed by a network which displays alternative potential evolutionary paths in the form of cycles. We present a method ("median joining" [MJ]) for constructing networks from recombination-free population data that combines features of Kruskal's algorithm for finding minimum spanning trees by favoring short connections, and Farris's maximum-parsimony (MP) heuristic algorithm, which sequentially adds new vertices called "median vectors", except that our MJ method does not resolve ties. The MJ method is hence closely related to the earlier approach of Foulds, Hendy, and Penny for estimating MP trees but can be adjusted to the level of homoplasy by setting a parameter epsilon. Unlike our earlier reduced median (RM) network method, MJ is applicable to multistate characters (e.g., amino acid sequences). An additional feature is the speed of the implemented algorithm: a sample of 800 worldwide mtDNA hypervariable segment I sequences requires less than 3 h on a Pentium 120 PC. The MJ method is demonstrated on a Tibetan mitochondrial DNA RFLP data set.
A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: Preclinical activity and safety in nonhuman primates
Authors: Gurunadh R. Chichili, Ling Huang, Hua Li, Steve Burke, Leilei He, Qin Tang, Linda Jin, Sergey Gorlatov, Valentina Ciccarone, Francine Chen, Scott Koenig, Michele Shannon, Ralph Alderson, Paul A. Moore, Syd Johnson, Ezio Bonvini
Journal: Science Translational Medicine (2015)

MGD006, a CD3xCD123 bispecific DART molecule intended for AML treatment, shows anticancer activity in mouse model and favorable pharmacodynamic and safety profile in nonhuman primates.
Reduction of Airway Smooth Muscle Mass by Bronchial Thermoplasty in Patients with Severe Asthma
Authors: Marina Pretolani, Marie-Christine Dombret, Gabriel Thabut, Dominique Knap, Fatima Hamidi, Marie-Pierre Debray, Camille Taille, Pascal Chanez, Michel Aubier
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Beta-blockers in cirrhosis patients with refractory ascites
Authors: Anne Robins, Anne Bowden, William Watson, Fiona Smith, William Gelson, William Griffiths
Journal: Hepatology (2013)

Because prothrombin time was lacking in our pooled data, we could not represent cirrhosis severity in this study.The study endpoint was HCC incidence over 1 year after the start of observation.Patients who developed HCC within 1 year were included in those with a follow-up duration <1 year.Therefore, patients with HCC or suspicion of HCC on enrollment were excluded from this study.It is impossible to avoid any bias because this study is a retrospective cohort study.We think that the method of this study is the next best method of ensuring that the experimental and control groups are similar in the absence of randomization, as Prof. Sherman described. 2Our findings are consistent with those recently published from Hong Kong. 3A recent meta-analysis, which included our results, demonstrated a reduction in HCC incidence with oral antiviral agents. 4 The risk reduction of HCC by nucleos(t)ide analogs needs to be confirmed in other long-term studies of ETV or tenofovir with high antiviral potency.
HAMSTRING MUSCLE ACTIVATION DURING HIGH-SPEED OVERGROUND RUNNING: IMPACT OF PREVIOUS STRAIN INJURY
Authors: M Bourne, D Opar, A Shield
Journal: British Journal of Sports Medicine (2014)

Background Hamstring strain injuries (HSIs) are a common and recurrent complaint in sport, with most insults occurring during high-speed overground running. Objective To determine, during high-speed overground running, the spatial patterns of hamstring muscle voluntary activation (VA) in limbs with and without a history of HSI. Design Retrospective cross-sectional study. Setting Elite and sub-elite level track and field (T&amp;F). Participants Five healthy, elite (n=4) and sub-elite (n=1) level T&amp;F athletes, with a history of unilateral HSI were recruited (average time of 6.5±3.9 months post-injury; average age 20±1.8 years; stature 182.1±6.5 cm and mass 78.3±4.8 kg). Assessment of risk factors Functional MRI was performed on participants thighs before and after 3 sets of 6, 40m sprints (30s rest between reps; 1 min rest between sets). T2 relaxation times of all hamstring muscles (biceps femoris long (BFlh) and short head (BFsh); semitendinosus (ST); semimembranosus (SM)), were measured at rest and immediately after the running protocol. Main outcome measurements The percentage change in T2 relaxation time for each hamstring muscle, in both the previously injured and contralateral uninjured limbs. Results For the spatial analysis of uninjured limbs, no significant differences were observed in the percentage increase in T2 relaxation for any muscles (BFlh vs ST, P=.07; BFlh vs BFsh, P=.66; BFlh vs SM, P=.08; BFsh vs ST, P=.08; BFsh vs SM, P=.54; SM vs ST, P=.57). However, previously injured hamstring muscles displayed significantly smaller increases in T2 relaxation time compared with homonymous muscles in the uninjured contralateral limb (mean difference=–8.1%, 95% CI=-16.5 to -0.3%, P=.02). Conclusions These preliminary findings indicate that the hamstrings of uninjured limbs are activated somewhat uniformly during high-speed overground running however, following an HSI, VA is chronically reduced in the previously injured muscle.
Inefficient clearance of myelin debris by microglia impairs remyelinating processes
Authors: Antoine Lampron, Antoine Larochelle, Nathalie Laflamme, Paul Préfontaine, Marie-Michèle Plante, Maria Gabriela Sánchez, V. Wee Yong, Peter K. Stys, Marie-Ève Tremblay, Serge Rivest
Journal: The Journal of Experimental Medicine (2015)

An imbalance between remyelinating and demyelinating rates underlies degenerative processes in demyelinating diseases such as multiple sclerosis. An optimal therapeutic strategy would be to stimulate remyelination while limiting demyelination. Although accumulation of myelin debris impairs remyelination, the mechanisms regulating the clearance of such debris by mononuclear phagocytic cells are poorly understood. We demonstrate that after cuprizone intoxication, CCR2-dependent infiltration of mouse bone marrow–derived cells is abundant in demyelinating areas, but that these cells do not impact demyelination. However, in CX3CR1-deficient mice, the clearance of myelin debris by microglia was blocked greatly, affecting the integrity of the axon and myelin sheaths and thus preventing proper remyelination. These results highlight the crucial role played by CX3CR1 in myelin removal and show that there can be no efficient remyelination after a primary demyelinating insult if myelin clearance by microglia is impaired.
Estimated GFR Associates with Cardiovascular Risk Factors Independently of Measured GFR
Authors: Ulla Dorte Mathisen, Toralf Melsom, Ole C. Ingebretsen, Trond Jenssen, Inger Njølstad, Marit D. Solbu, Ingrid Toft, Bjørn O. Eriksen
Journal: Journal of the American Society of Nephrology (2011)

Estimation of the GFR (eGFR) using creatinine- or cystatin C-based equations is imperfect, especially when the true GFR is normal or near-normal. Modest reductions in eGFR from the normal range variably predict cardiovascular morbidity. If eGFR associates not only with measured GFR (mGFR) but also with cardiovascular risk factors, the effects of these non-GFR-related factors might bias the association between eGFR and outcome. To investigate these potential non-GFR-related associations between eGFR and cardiovascular risk factors, we measured GFR by iohexol clearance in a sample from the general population (age 50 to 62 years) without known cardiovascular disease, diabetes, or kidney disease. Even after adjustment for mGFR, eGFR associated with traditional cardiovascular risk factors in multiple regression analyses. More risk factors influenced cystatin C-based eGFR than creatinine-based eGFR, adjusted for mGFR, and some of the risk factors exhibited nonlinear effects in generalized additive models (P<0.05). These results suggest that eGFR, calculated using standard creatinine- or cystatin C-based equations, partially depends on factors other than the true GFR. Thus, estimates of cardiovascular risk associated with small changes in eGFR must be interpreted with caution.
Immunostimulation Versus Immunosuppression after Multiple Vaccinations: the Woes of Therapeutic Vaccine Development
Authors: Alexander M.M. Eggermont
Journal: Clinical Cancer Research (2009)

Three articles in this issue of Clinical Cancer Research show how multiple vaccinations can lead to immunosuppression. Moreover, two studies in patients show that granulocyte macrophage colony-stimulating factor (GM-CSF) as an adjuvant immunostimulant to different kind of vaccines can lead to adverse outcome in terms of relapse-free and overall survival. Modulation of regulatory T-cell activity may be required to overcome this outcome and may be crucial for the successful development of therapeutic vaccines.
Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and Allergies in Childhood (ISAAC) data
Authors: P. Ellwood, M.I. Asher, B. Björkstén, M. Burr, N. Pearce, C.F Robertson
Journal: European Respiratory Journal (2001)

Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data. Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6–7 and 13–14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995). The 13–14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13–14 yr olds and the ISAAC data for 6–7 yr olds showed similar patterns for these foods. A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.
Effects of chronic low dose rotenone treatment on human microglial cells
Authors: Shamim B Shaikh, Louise FB Nicholson
Journal: Molecular Neurodegeneration (2009)

Exposure to toxins/chemicals is considered to be a significant risk factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is the naturally occurring herbicide rotenone that is now used widely in establishing PD models. We, and others, have shown that chronic low dose rotenone treatment induces excessive accumulation of Reactive Oxygen Species (ROS), inclusion body formation and apoptosis in dopaminergic neurons of animal and human origin. Some studies have also suggested that microglia enhance the rotenone induced neurotoxicity. While the effects of rotenone on neurons are well established, there is little or no information available on the effect of rotenone on microglial cells, and especially cells of human origin. The aim of the present study was to investigate the effects of chronic low dose rotenone treatment on human microglial CHME-5 cells. We have shown previously that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y cells and therefore used these cells as a control for inclusion body formation in this study. SH-SY5Y and CHME-5 cells were treated with 5 nM rotenone for four weeks. At the end of week 4, both cell types were analysed for the presence of inclusion bodies, superoxide dismutases and cell activation (only in CHME-5 cells) using Haematoxylin and Eosin staining, immunocytochemical and western blotting methods. Levels of active caspases and ROS (both extra and intra cellular) were measured using biochemical methods. The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others. However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low dose) induced damage.
Induction of long-term H-Y-specific tolerance in female mice given male lymphoid cells while transiently depleted of CD4+ or CD8+ T cells.
Authors: F P VanderVegt, L L Johnson
Journal: The Journal of Experimental Medicine (1993)

Rejection of H-Y-bearing primary skin grafts and generation of H-Y-specific cytolytic T cells by female mice requires the participation of both CD4+ and CD8+ T lymphocytes. Studies were conducted to investigate long-term tolerance of H-Y antigen induced in female mice by transiently depleting them of CD4+ and/or CD8+ T cells and, at the same time, giving them an injection of male lymphoid cells. We confirmed that after recovery of CD4+ to normal levels, female mice that had been transiently depleted of CD4+ cells and concurrently given an injection of male spleen cells were unable to generate H-Y-specific cytolytic T cells. Tolerance was also manifest by greatly extended survival (probably permanent in most cases) of male skin grafts. Further investigations revealed that female mice transiently depleted of CD8+ cells, and concurrently given an injection of male spleen cells, were similarly tolerant of H-Y antigen later when numbers of CD8+ T cells returned to normal. Moreover, small numbers of male cells were detectable in spleen and lymph nodes of tolerant females long after they had been given an injection of male cells and depleted of either CD4+ or CD8+ T cells, whereas no male cells were detected in (nontolerant) females given male cells and control antibodies. These findings show that tolerance of the relatively weak transplantation antigen, H-Y, can be achieved simply by giving male antigen-bearing spleen cells to the host while it is transiently depleted of a type of cell it needs in order to reject those cells, thus allowing the male cells to persist in the host. Furthermore, depletion of helper cells is not obligatory to achieve tolerance. It has been hypothesized that tolerance of H-Y antigen in females given male lymphoid cells while temporarily depleted of CD4+ lymphocytes results from unresponsiveness (anergy) induced in H-Y-specific CD8+ cells that are exposed to H-Y antigen in the absence of help from CD4+ cells. Interpretations of our findings are discussed in relation to this hypothesis.
Soccer &amp; science--in an interdisciplinary perspective
Authors: K Arjun Rao
Journal: British Journal of Sports Medicine (2007)

Edited by Jens Bangsbo. Blackwell Publishing:Carlton, Victoria, Australia; 2000, pp 151. ISBN 87-16-12348-4

With a timely release prior to the 2006 World Cup in Germany, much was anticipated. I gather the idea was conceived at the second European Congress of Sport and Exercise Science held in Copenhagen in August 1997. This is part of a series of books, which includes other activities such as running and sailing.

The front cover is certainly interesting, with an abstract painting—largely in the Swedish, Norweigan and Argentinian colours I might add! This book approaches soccer …
Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A
Authors: Sandra Ciesek, Eike Steinmann, Heiner Wedemeyer, Michael P. Manns, Johann Neyts, Norbert Tautz, Vanesa Madan, Ralf Bartenschlager, Thomas von Hahn, Thomas Pietschmann
Journal: Hepatology (2009)

Abstract Numerous anti-hepatitis C virus (HCV) drugs targeting either the viral nonstructural 3 (NS3) protease or NS5B polymerase are currently in clinical testing. However, rapid resistance development is a major problem and optimal therapy will clearly require a combination of multiple mechanisms of action. Cyclosporine A (CsA) and its nonimmunosuppressant derivatives are among the more promising drugs under development. Based on work with subgenomic HCV replicons it has been thought that they act as NS5B-inhibitors. In this study we show that CsA inhibits replication of full-length HCV Japanese Fulminant Hepatitis (JFH1) genomes about 10-fold more efficiently than subgenomic replicons. This effect is dependent on the presence of NS2 in the viral polyprotein and mediated through cellular cyclophilin A. NS2 is either an additional target for CsA-dependent inhibition or modulates the antiviral activity against NS3 to NS5B proteins. CsA is thus the first anti-HCV drug shown to act through NS2. Conclusion: CsA inhibits replication of JFH1 full-length genomes much more efficiently than subgenomic replicons by targeting cleavage at the NS2/NS3 junction and possibly other nonreplication lifecycle steps. (Hepatology 2009.)