tbuckley/cabot-search huggingface dataset:
Genome-Wide Association Study of Event-Free Survival in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy
Authors: Hervé Ghesquieres, Susan L. Slager, Fabrice Jardin, Amelie S. Veron, Yan W. Asmann, Matthew J. Maurer, Thierry Fest, Thomas M. Habermann, Marie C. Bene, Anne J. Novak, Sylvain Mareschal, Corinne Haioun, Thierry Lamy, Stephen M. Ansell, Herve Tilly, Thomas E. Witzig, George J. Weiner, Andrew L. Feldman, Ahmet Dogan, Julie M. Cunningham, Curtis L. Olswold, Thierry Jo Molina, Brian K. Link, Noel Milpied, David G. Cox, Gilles A. Salles, James R. Cerhan
Journal: Journal of Clinical Oncology (2015)

We performed a multistage genome-wide association study to identify inherited genetic variants that predict outcome in diffuse large B-cell lymphoma patients treated with immunochemotherapy.We conducted a meta-analysis of two genome-wide association study data sets, one from the LNH2003B trial (N = 540), a prospective clinical trial from the Lymphoma Study Association, and the other from the Molecular Epidemiology Resource study (N = 312), a prospective observational study from the University of Iowa-Mayo Clinic Lymphoma Specialized Program of Research Excellence. Top single nucleotide polymorphisms were then genotyped in independent cohorts of patients from the Specialized Program of Research Excellence (N = 391) and the Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang (GOELAMS) -075 randomized trial (N = 294). We calculated the hazard ratios (HRs) and 95% CIs for event-free survival (EFS) and overall survival (OS) using a log-additive genetic model with adjustment for age, sex, and age-adjusted International Prognostic Index.In a meta-analysis of the four studies, the top loci for EFS were marked by rs7712513 at 5q23.2 (near SNX2 and SNCAIP; HR, 1.39; 95% CI, 1.23 to 1.57; P = 2.08 × 10(-7)), and rs7765004 at 6q21 (near MARCKS and HDAC2; HR, 1.38; 95% CI, 1.22 to 1.57; P = 7.09 × 10(-7)), although they did not reach conventional genome-wide significance (P = 5 × 10(-8)). Both rs7712513 (HR, 1.49; 95% CI, 1.29 to 1.72; P = 3.53 × 10(-8)) and rs7765004 (HR, 1.47; 95% CI, 1.27 to 1.71; P = 5.36 × 10(-7)) were also associated with OS. In exploratory analyses, a two-single nucleotide polymorphism risk score was highly predictive of EFS (P = 1.78 × 10(-12)) and was independent of treatment, IPI, and cell-of-origin classification.Our study provides encouraging evidence for associations between loci at 5q23.2 and 6q21 with EFS and OS in patients with diffuse large B-cell lymphoma treated with immunochemotherapy, suggesting novel biology and the potential contribution of host genetics to the prognosis of this aggressive malignancy.
Artistic brain-computer interfaces: state-of-the-art control mechanisms
Authors: Amy Wadeson, Anton Nijholt, Chang S. Nam
Journal: Brain-Computer Interfaces (2015)

Artistic BCI applications offer a new modality for humans to express themselves creatively. In this survey we reviewed the available literature on artistic BCIs by classifying four types of user control afforded by the available applications: selective control, passive control, direct control and collaborative control. A brief overview of the history of artistic BCIs is presented, followed by examples of current artistic BCI applications in each defined sector of control. We questioned whether or not creative control affects the users' sense of enjoyment or satisfaction. Finally, we made suggestions for the future of artistic BCI research to question the role that control plays in user satisfaction and entertainment.
Energy Partitioning and Modeling in Animal Nutrition
Authors: R. L. Baldwin, R. D. Sainz
Journal: Annual Review of Nutrition (1995)

We first present a brief discussion of early and current models (feeding systems) used to estimate animal energy and protein requirements and to predict performance based on feed composition and intake. We then touch on some limitations inherent in these systems. Next, we propose that dynamic (i.e. time-variant) models and mechanistic models (i.e. equations based on knowledge of physiological functions) are superior to earlier systems for both practical and research applications. Finally, we describe a number of applied and research models of animal growth and lactation to illustrate how biological concepts may be represented in equation form. Equations that represent current knowledge of underlying functions can be used to improve predictions of animal requirements and performance and to evaluate hypotheses about nutritional and physiological mechanisms that influence animal performance.
The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1
Authors: M Larrayoz, S J Blakemore, R C Dobson, M D Blunt, M J J Rose-Zerilli, R Walewska, A Duncombe, D Oscier, K Koide, F Forconi, G Packham, M Yoshida, M S Cragg, J C Strefford, A J Steele
Journal: Leukemia (2015)
Abstract 16859: Does Glagov's Phenomenon Work in Reverse? A Preliminary Cardiovascular MRI Observation
Authors: Sobhan Kodali, Mark Doyle, David R Neff, Saundra B Grant, Ronald B Williams, June A Yamrozik, Geetha Rayarao, George Angheloiu, Vikas K Rathi, Robert W Biederman
Journal: Circulation (2010)

Introduction: According to Glagov's phenomenon, the early stages of atherogenesis (stenosis <40%) are associated with positive remodeling of the outer arterial wall Resultsing in paradoxical preser...
Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and Long-Term Outcomes of a Single-Blind Randomized Study
Authors: A. John Rush, Madhukar H. Trivedi, Jonathan W. Stewart, Andrew A. Nierenberg, Maurizio Fava, Benji T. Kurian, Diane Warden, David W. Morris, James F. Luther, Mustafa M. Husain, Ian A. Cook, Richard C. Shelton, Ira M. Lesser, Susan G. Kornstein, Stephen R. Wisniewski
Journal: American Journal of Psychiatry (2011)

Objective: Two antidepressant medication combinations were compared with selective serotonin reuptake inhibitor monotherapy to determine whether either combination produced a higher remission rate in first-step acute-phase (12 weeks) and long-term (7 months) treatment. Method: The single-blind, prospective, randomized trial enrolled 665 outpatients at six primary and nine psychiatric care sites. Participants had at least moderately severe nonpsychotic chronic and/or recurrent major depressive disorder. Escitalopram (up to 20 mg/day) plus placebo, sustained-release bupropion (up to 400 mg/day) plus escitalopram (up to 20 mg/day), or extended-release venlafaxine (up to 300 mg/day) plus mirtazapine (up to 45 mg/day) was delivered (1:1:1 ratio) by using measurement-based care. The primary outcome was remission, defined as ratings of less than 8 and less than 6 on the last two consecutive applications of the 16-item Quick Inventory of Depressive Symptomatology—Self-Report. Secondary outcomes included side effect burden, adverse events, quality of life, functioning, and attrition. Results: Remission and response rates and most secondary outcomes were not different among treatment groups at 12 weeks. The remission rates were 38.8% for escitalopram-placebo, 38.9% for bupropion-escitalopram, and 37.7% for venlafaxine-mirtazapine, and the response rates were 51.6%–52.4%. The mean number of worsening adverse events was higher for venlafaxine-mirtazapine (5.7) than for escitalopram-placebo (4.7). At 7 months, remission rates (41.8%–46.6%), response rates (57.4%–59.4%), and most secondary outcomes were not significantly different. Conclusions: Neither medication combination outperformed monotherapy. The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events.
Mismatches In Killer Immunoglobulin Receptor (KIR) Ligands and Inhibitory KIR Receptors Between Donor and Recipients Improve Survival After Non T Cell Depleted Haploidentical Transplantation
Authors: Mariana Bastos-Oreiro, Javier Anguita, Carolina Martínez-Laperche, Almudena Navarro, Lucía Fernandez, Pascual Balsalobre, Cristina Muñoz, Mi Kwon, Ana Perez, Cristina Pascual, Antonio Perez, Ismael Buno, Jorge Gayoso, Jose Luis Díez
Journal: Blood (2013)
Prophylaxis of Infective Endocarditis: A Reevaluation
Authors: J N Sipes, R L Thompson, E W Hook
Journal: Annual Review of Medicine (1977)

Established practice dictates that physicians and dentists give antimicrobial agents at the time of procedures associated with bacteremia in an effort to prevent IE in persons with underlying cardiovascular diseases. Although prospective controlled study has not been established efficacy, very few cases of IE have been reported in patients at risk who have been treated with regimens recommended by the American Heart Association. Furthermore, studies in rabbits in recent years have shown that IE can be prevented by antimicrobials. The results in rabbits have raised some theoretical questions regarding efficacy of currently recommended regimens for man and have led some investigators to propose revisions of the American Heart Association recommendations. We feel that direct translation of results from experimental IE in rabbits into recommendations for prophylaxis of IE in man is subject to question. It is unlikely that a prospective study comparing placebo with antimicrobials will be undertaken, but it is possible and reasonable to undertake studies to document the occurrence of IE in patients at risk who are given established antibiotic regimens. With such data, modifications of established regimens could be proposed and tested. Regimens that are found to be totally effective in a large number of patients at risk might be modified toward simpler programs--for example, modifying parenteral therapy to oral therapy or changing multiple doses of antibiotic to a single dose. If regimens fail, even once in several thousand patients at risk, the factors responsible might be determined and a clear rationale for modification achieved.
First-in-Human Phase I Study of Lumretuzumab, a Glycoengineered Humanized Anti-HER3 Monoclonal Antibody, in Patients with Metastatic or Advanced HER3-Positive Solid Tumors
Authors: Didier Meulendijks, Wolfgang Jacob, Maria Martinez-Garcia, Alvaro Taus, Martijn P. Lolkema, Emile E. Voest, Marlies H.G. Langenberg, Tania Fleitas Kanonnikoff, Andres Cervantes, Maja J. De Jonge, Stefan Sleijfer, Morten Mau Soerensen, Marlene Thomas, Maurizio Ceppi, Georgina Meneses-Lorente, Ian James, Celine Adessi, Francesca Michielin, Keelara Abiraj, Birgit Bossenmaier, Jan H.M. Schellens, Martin Weisser, Ulrik N. Lassen
Journal: Clinical Cancer Research (2015)

A first-in-human phase I study was conducted to characterize safety, efficacy, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of lumretuzumab, a humanized and glycoengineered anti-HER3 monoclonal antibody, in patients with advanced cancer.Twenty-five patients with histologically confirmed HER3-expressing tumors received lumretuzumab (100, 200, 400, 800, 1,600, and 2,000 mg) every two weeks (q2w) in 3+3 dose-escalation phase. In addition, 22 patients were enrolled into an extension cohort at 2,000 mg q2w.There were no dose-limiting toxicities. Common adverse events (any grade) included diarrhea (22 patients, 46.8%), fatigue (21 patients, 44.7%), decreased appetite (15 patients, 31.9%), infusion-related reactions (13 patients, 27.7%), and constipation (10 patients, 21.3%). The peak concentration (Cmax) and area under the concentration-time curve up to the last measurable concentration (AUClast) of lumretuzumab increased more than dose proportionally from 100 mg up to 400 mg. Linear PK was observed with doses ≥ 400 mg q2w indicating target-mediated drug disposition saturation. Downregulation of HER3 membranous protein was observed in on-treatment tumor biopsies from 200 mg, and was maximal at and above 400 mg. An ex vivo assay demonstrated increased activation potential of peripheral NK lymphocytes with lumretuzumab compared with a non-glycoengineered anti-HER3 antibody. Ten patients (21.3%) had stable disease and remained on study at a median of 111 days (range, 80-225 days).Lumretuzumab was well tolerated and showed evidence of clinical activity. Linear serum PK properties and plateauing of PD effects in serial tumor biopsies indicate optimal biologically active doses of lumretuzumab from 400 mg onwards.
Orthotopic transplantation of a tissue engineered diaphragm in rats
Authors: Elena A. Gubareva, Sebastian Sjöqvist, Irina V. Gilevich, Alexander S. Sotnichenko, Elena V. Kuevda, Mei Ling Lim, Neus Feliu, Greg Lemon, Konstantin A. Danilenko, Ramazan Z. Nakokhov, Ivan S. Gumenyuk, Timofei E. Grigoriev, Sergey V. Krasheninnikov, Alexander G. Pokhotko, Alexander A. Basov, Stepan S. Dzhimak, Ylva Gustafsson, Geoanna Bautista, Antonio Beltrán Rodríguez, Vladimir M. Pokrovsky, Philipp Jungebluth, Sergei N. Chvalun, Mark J. Holterman, Doris A. Taylor, Paolo Macchiarini
Journal: Biomaterials (2015)
Mitoxantrone, Etoposide, and Cyclosporine Therapy in Pediatric Patients With Recurrent or Refractory Acute Myeloid Leukemia
Authors: Gary V. Dahl, Norman J. Lacayo, Nathalie Brophy, Kyriaki Dunussi-Joannopoulos, Howard J. Weinstein, Myron Chang, Branimir I. Sikic, Robert J. Arceci
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the remission rate and toxicity of mitoxantrone, etoposide, and cyclosporine (MEC) therapy, multidrug resistance-1 (MDR1) status, and steady-state cyclosporine (CSA) levels in children with relapsed and/or refractory acute myeloid leukemia. PATIENTS AND METHODS: MEC therapy consisted of mitoxantrone 6 mg/m 2 /d for 5 days, etoposide 60 mg/m 2 /d for 5 days, and CSA 10 mg/kg for 2 hours followed by 30 mg/kg/d as a continuous infusion for 98 hours. Because of pharmacokinetic interactions, drug doses were decreased to 60% of those found to be effective without coadministration of CSA. MDR1 expression was evaluated by reverse transcriptase polymerase chain reaction, flow cytometry, and the ability of CSA at 2.5 μmol/L to increase intracellular accumulation of 3 H-daunomycin in blasts from bone marrow specimens. RESULTS: The remission rate was 35% (n = 23 of 66). Overall, 35% of patients (n = 23) achieved complete remission (CR), 12% of patients (n = 8) achieved partial remission, and 9% of patients (n = 6) died of infection. Exposure to CSA levels of greater than 2,400 ng/mL was achieved in 95% of patients (n = 56 of 59). Toxicities included infection, cardiotoxicity, myelosuppression, stomatitis, and reversible increases in serum creatinine and bilirubin. In most who had relapsed while receiving therapy or whose induction therapy had failed, response was not significantly different for MDR1-positive and MDR1-negative patients. CONCLUSION: Serum levels of CSA capable of reversing multidrug resistance are achievable in children with acceptable toxicity. The CR rate of 35% achieved in this study is comparable to previously reported results using standard doses of mitoxantrone and etoposide. The use of CSA may have improved the response rate for the MDR1-positive patients so that it was not different from that for the MDR1-negative patients.
HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice
Authors: Jannick Prentoe, Lieven Verhoye, Rodrigo Velázquez Moctezuma, Caroline Buysschaert, Ali Farhoudi, Richard Wang, Harvey Alter, Philip Meuleman, Jens Bukh
Journal: Gut (2015)

<h3>Objective</h3> HCV is a major cause of chronic liver disease worldwide, but the role of neutralising antibodies (nAbs) in its natural history remains poorly defined. We analysed the in vivo role of hypervariable region 1 (HVR1) for HCV virion properties, including nAb susceptibility. <h3>Design</h3> Analysis of HCV from human liver chimeric mice infected with cell-culture-derived prototype genotype 2a recombinant J6/JFH1 or HVR1-deleted variant J6/JFH1<sub>ΔHVR1</sub> identified adaptive mutations, which were analysed by reverse genetics in Huh7.5 and CD81-deficient S29 cells. The increased in vivo genomic stability of the adapted viruses facilitated ex vivo density analysis by ultracentrifugation and in vivo neutralisation experiments addressing the role of HVR1. <h3>Results</h3> In vivo, J6/JFH1 and J6/JFH1<sub>ΔHVR1</sub> depended on single substitutions within amino acids 867–876 in non-structural protein, NS2. The identified A876P-substitution resulted in a 4.7-fold increase in genomic stability. In vitro, NS2 substitutions enhanced infectivity 5–10-fold by increasing virus assembly. Mouse-derived mJ6/JFH1<sub>A876P</sub> and mJ6/JFH1<sub>ΔHVR1/A876P</sub> viruses displayed similar heterogeneous densities of 1.02–1.1 g/mL. Human liver chimeric mice loaded with heterologous patient H (genotype 1a) immunoglobulin had partial protection against mJ6/JFH1<sub>A876P</sub> and complete protection against mJ6/JFH1<sub>ΔHVR1/A876P</sub>. Interestingly, we identified a putative escape mutation, D476G, in mJ6/JFH1<sub>A876P</sub>. This mutation in hypervariable region 2 conferred 6.6-fold resistance against H06 IgG in vitro. <h3>Conclusions</h3> The A876P-substitution bridges in vitro and in vivo studies using J6/JFH1-based recombinants. We provide the first in vivo evidence that HVR1 protects cross-genotype conserved HCV neutralisation epitopes, which advocates the possibility of using HVR1-deleted viruses as vaccine antigens to boost broadly reactive protective nAb responses.
Global Pediatric Oncology: Lessons From Partnerships Between High-Income Countries and Low- to Mid-Income Countries
Authors: Raul C. Ribeiro, Federico Antillon, Francisco Pedrosa, Ching-Hon Pui
Journal: Journal of Clinical Oncology (2015)

Partnerships between medical institutions in high-income countries (HICs) and low- to mid-income countries (LMICs) have succeeded in initiating and expanding pediatric cancer control efforts. The long-term goal is consistently a sustainable national pediatric cancer program. Here, we review the elements required for successful implementation, development, and long-term sustainability of pediatric cancer programs in LMICs that first arise as partnerships with institutions in HICs. Although plans must be adapted to each country's resources, certain components are unfailingly necessary. First, an essential step is provision of treatment regardless of ability to pay. Second, financial support for program development and long-term sustainability must be sought from sources both international and local, public and private. A local leader, typically a well-trained pediatric oncologist who devotes full-time effort to the project, should direct medical care and collaborate with hospital, governmental, and community leadership and international agencies. Third, nurses must be trained in pediatric cancer care and allowed to practice this specialty full-time. It is also essential to develop a grassroots organization, such as a foundation, dedicated solely to pediatric oncology. Its members must be trained and educated to provide pediatric cancer advocacy, fundraising, and (in concert with government) program sustainability. Finally, a project mentor in the HIC is crucial and should explore the possibility of collaborative research in the LMIC, which may offer significant opportunities. Relationships between the partnership's leaders and influential individuals in the community, hospital, grassroots foundation, and government will lay the foundation for productive collaboration and a sustainable pediatric oncology program.
Counselling will be needed when embryos are donated as well as when they are stored
Authors: S. Maguiness, J. Robinson, S. Killick
Journal: BMJ (1996)

EDITOR,—We agree with Alan Trounson and Karen Dawson that the ability to cryopreserve embryos has presented both opportunities and dilemmas.1 The authors suggest that consent be obtained at the time of storage, and this may have organisational advantages. Nevertheless, …
Research in progress—LungSEARCH: a randomised controlled trial of surveillance for the early detection of lung cancer in a high-risk group
Authors: Stephen G Spiro, Allan Hackshaw
Journal: Thorax (2015)

Low-dose CT screening for lung cancer is effective but expensive. Therefore, cheaper or more focused screening strategies may be required. LungSEARCH is a randomised prospective trial of 1568 high-risk individuals (ie, current or former moderate to heavy smokers with mild/moderate COPD) who undergo either annual sputum cytology/cytometry testing or no screening. Those with abnormal sputum then receive annual CT and fluorescent bronchoscopy for the remainder of 5 years, to identify early stage lung cancer. It is hoped that these simple initial tests could identify those requiring expensive CT scans, and the aim is to demonstrate a stage shift towards early stage cancers. Trial registration numbers ISRCTN: ISRCTN80745975 , clinicaltrials.gov: NCT00512746 .
Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium
Authors: Tina Young Poussaint, Sridhar Vajapeyam, Kelsey I. Ricci, Ashok Panigrahy, Mehmet Kocak, Larry E. Kun, James M. Boyett, Ian F. Pollack, Maryam Fouladi
Journal: Neuro-Oncology (2015)

Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). Baseline and post-RT quantitative ADC histograms were generated from fluid-attenuated inversion recovery (FLAIR) images and enhancement regions of interest. Metrics assessed included number of peaks (ie, unimodal or bimodal), mean and median ADC, standard deviation, mode, skewness, and kurtosis. Based on FLAIR images, the majority of tumors had unimodal peaks with significantly shorter average survival. Pre-RT FLAIR mean, mode, and median values were significantly associated with decreased risk of progression; higher pre-RT ADC values had longer PFS on average. Pre-RT FLAIR skewness and standard deviation were significantly associated with increased risk of progression; higher pre-RT FLAIR skewness and standard deviation had shorter PFS. Nonenhancing tumors at baseline showed higher ADC FLAIR mean values, lower kurtosis, and higher PFS. For enhancing tumors at baseline, bimodal enhancement histograms had much worse PFS and OS than unimodal cases and significantly lower mean peak values. Enhancement in tumors only after RT led to significantly shorter PFS and OS than in patients with baseline or no baseline enhancement. ADC histogram metrics in DIPG demonstrate significant correlations between diffusion metrics and survival, with lower diffusion values (increased cellularity), increased skewness, and enhancement associated with shorter survival, requiring future investigations in large DIPG clinical trials.