tbuckley/cabot-search huggingface dataset:
Estimation of evolutionary distance between nucleotide sequences.
Authors: F Tajima, M Nei
Journal: Molecular Biology and Evolution (1984)

A mathematical formula for estimating the average number of nucleotide substitutions per site (delta) between two homologous DNA sequences is developed by taking into account unequal rates of substitution among different nucleotide pairs. Although this formula is obtained for the equal-input model of nucleotide substitution, computer simulations have shown that it gives a reasonably good estimate for a wide range of nucleotide substitution patterns as long as delta is equal to or smaller than 1. Furthermore, the frequency of cases to which the formula is inapplicable is much lower than that for other similar methods recently proposed. This point is illustrated using insulin genes. A statistical method for estimating the number of nucleotide changes due to deletion and insertion is also developed. Application of this method to globin gene data indicates that the number of nucleotide changes per site increases with evolutionary time but the pattern of the increase is quite irregular.
Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literature
Authors: I. Uçkay, A. Dinh, L. Vauthey, N. Asseray, N. Passuti, M. Rottman, J. Biziragusenyuka, A. Riché, P. Rohner, D. Wendling, S. Mammou, R. Stern, P. Hoffmeyer, L. Bernard
Journal: Clinical Microbiology and Infection (2009)
The Interleukin 7 Receptor Is Required for T Cell Receptor γ Locus Accessibility to the V(D)j Recombinase
Authors: Mark S. Schlissel, Scott D. Durum, Kathrin Muegge
Journal: The Journal of Experimental Medicine (2000)

Defects in the interleukin (IL)-7 signal transduction pathway lead to severe immunodeficiency in humans and in mice. In IL-7 receptor–deficient (IL-7R−/−) mice, lymphoid precursors show a reduced survival rate and variable/diversity/joining region V(D)J recombination is variously affected in different loci, being arrested in the T cell receptor (TCR)-γ locus, aberrant in the immunoglobulin heavy chain (IgH) locus, and delayed in the TCR-β locus. Here, we analyze the recombination defect of the TCR-γ locus. Using ligation-mediated polymerase chain reaction, we sought intermediates of the recombination process. In the absence of the IL-7 signal, no initiation of recombination of the TCR-γ locus was observed, whereas recombination intermediates at the TCR-β locus could be detected. Thus, the failure to rearrange the TCR-γ locus is due to a failure to initiate cleavage rather than a failure to religate broken DNA ends. V(D)J recombination was previously thought to begin at the pro-T2 stage of T cell development after the arrest of IL-7R−/− thymocytes at the pro-T1 stage. However, here we show that both TCR-γ and -β recombination intermediates are readily detectable in normal T1 cells, but only TCR-β intermediates were detected in IL-7R−/− T1 cells, supporting a mechanistic role for IL-7 in TCR-γ locus rearrangement. Since reduced recombination activating gene (rag) expression has been reported in the absence of the IL-7 signal, we directly tested whether the TCR-γ locus is accessible to cleavage by recombinant Rag proteins in vitro. We found a reduction in chromatin accessibility for Rag-mediated cleavage in IL-7R−/− thymocytes compared with wild-type. Thus, IL-7 controls recombination at the TCR-γ locus by regulating locus accessibility.
Demographic, behavioural and physician‐related determinants of early melanoma detection in a low‐incidence population
Authors: J.A. Talaganis, K. Biello, M. Plaka, D. Polydorou, O. Papadopoulos, M. Trakatelli, D. Sotiriadis, D. Tsoutsos, G. Kechagias, H. Gogas, C. Antoniou, S.M. Swetter, A.C. Geller, A.J. Stratigos
Journal: British Journal of Dermatology (2014)

Knowledge of the factors that influence early detection of melanoma is important in developing strategies to reduce associated mortality. To identify sociodemographic, behavioural and medical care‐related factors associated with melanoma thickness in a low‐incidence population but with a high case fatality. In a multicentre, retrospective, survey‐based study of 202 patients with a recent diagnosis of invasive melanoma (< 1 year), we collected data on demographic and behavioural factors, attitudes towards prevention, access to medical care, frequency of skin self‐examination (SSE) and physician skin examination (PSE) in relation to melanoma thickness. Thinner tumours (≤ 1 mm, 80 melanomas) were associated with female sex (P ≤0·049), nonnodular (superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanoma) histological subtypes (P <0·001), absence of ulceration (P ≤0·001), and location other than lower extremity or trunk location (P ≤0·004). Patients married at the time of diagnosis or who performed SSE during the year prior to diagnosis were more likely to have thinner tumours than those who did not [odds ratio (OR) 3·45, 95% confidence interval (CI) 1·48–8·04 and OR 2·43, 95% CI 1·10–5·34, respectively]. Full‐body skin examination by a physician was not significantly associated with thinner melanoma (OR 1·99, 95% CI 0·66–6·07). SSE was shown to be an important factor in the detection of thin melanoma, in contrast to partial or full‐body PSE, which did not show any statistically significant effect on tumour thickness.
The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study
Authors: R Terkeltaub, J S Sundy, H R Schumacher, F Murphy, S Bookbinder, S Biedermann, R Wu, S Mellis, A Radin
Journal: Annals of the Rheumatic Diseases (2009)

Recent studies suggest that blockade of the NLRP3 (cryopyrin) inflammasome interleukin 1beta (IL1beta) pathway may offer a new treatment strategy for gout.To explore the potential utility of rilonacept (IL1 Trap) in patients with chronic active gouty arthritis in a proof-of-concept study.This 14-week, multicentre, non-randomised, single-blind, monosequence crossover study of 10 patients with chronic active gouty arthritis included a placebo run-in (2 weeks), active rilonacept treatment (6 weeks) and a 6-week post-treatment follow-up.Rilonacept was generally well tolerated. No deaths and no serious adverse events occurred during the study. One patient withdrew owing to an injection-site reaction. Patients' self-reported median pain visual analogue scale scores significantly decreased from week 2 (after the placebo run-in) to week 4 (2 weeks of rilonacept) (5.0 to 2.8; p<0.049), with sustained improvement at week 8 (1.3; p<0.049); 5 of 10 patients reported at least a 75% improvement. Median symptom-adjusted and severity-adjusted joint scores were significantly decreased. High-sensitivity C-reactive protein levels fell significantly.This proof-of-concept study demonstrated that rilonacept is generally well tolerated and may offer therapeutic benefit in reducing pain in patients with chronic refractory gouty arthritis, supporting the need for larger, randomised, controlled studies of IL1 antagonism such as with rilonacept for this clinical indication.
IMMEDIATE INCREASES IN PLASMA PROLACTIN AND NEUROPHYSIN BUT NOT OTHER HORMONES AFTER ELECTROCONVULSIVE THERAPY
Authors: LawrenceJ. Whalley, Heinz Dick, AlanG. Watts, JaniceE. Christie, Roberta Rosie, Graciela Levy, WilliamJ. Sheward, George Fink
Journal: The Lancet (1982)
Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study
Authors: Eiso Hiyama, Tomoko Iehara, Tohru Sugimoto, Masahiro Fukuzawa, Yutaka Hayashi, Fumiaki Sasaki, Masahiko Sugiyama, Satoshi Kondo, Akihiro Yoneda, Hiroaki Yamaoka, Tatsuro Tajiri, Kohei Akazawa, Megu Ohtaki
Journal: The Lancet (2008)
A phase I/II trial of vandetanib for patients with recurrent malignant glioma
Authors: T. N. Kreisl, K. A. McNeill, J. Sul, F. M. Iwamoto, J. Shih, H. A. Fine
Journal: Neuro-Oncology (2012)

Vandetanib is a once-daily multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor–2, epidermal growth factor receptor, and the rearranged-during-transfection oncogene. A phase I trial was conducted to describe the pharmacokinetics of vandetanib in patients with recurrent glioma on enzyme-inducing anti-epileptic drugs (EIAEDs) and to identify the maximum tolerated dose (MTD) in this population. A phase II trial evaluated the efficacy of vandetanib in patients with recurrent malignant glioma not on EIAEDs as measured by 6-month progression-free survival (PFS6). In the phase I trial, 15 patients were treated with vandetanib at doses of 300, 400, and 500 mg/day, in a standard dose-escalation design. The MTD in patients on EIAEDs was 400 mg/day, and steady-state levels were similar to those measured in patients not on EIAEDs. Dose-limiting toxicities were prolonged QTc and thromboembolism. Thirty-two patients with recurrent glioblastoma multiforme (GBM) and 32 patients with recurrent anaplastic gliomas (AGs) were treated in the phase II trial, at a dosage of 300 mg/day on 28-day cycles. Six patients (4 GBM, 2 AG) had radiographic response. PFS6 was 6.5% in the GBM arm and 7.0% in the AG arm. Median overall survival was 6.3 months in the GBM arm and 7.6 months in the AG arm. Seizures were an unexpected toxicity of therapy. Vandetanib did not have significant activity in unselected patients with recurrent malignant glioma.
A controlled trial of a protein-free liver extract in the treatment of chronic liver disease
Authors: P. J. Toghill, R. P. Knill-Jones, R. Williams
Journal: Gut (1969)

A double-blind trial of a protein-free liver extract (Ripason) which was administered both orally and intramuscularly is described in 20 patients with stable cirrhosis. Control and treated groups were similar in composition except for age. Both groups showed some symptomatic improvement during the trial. Fewer patients were recorded as worse on Ripason but no significant changes in body weight, haemoglobin, or liver function tests could be detected.
Effect of Posterolateral Scar Tissue on Clinical and Echocardiographic Improvement After Cardiac Resynchronization Therapy
Authors: Gabe B. Bleeker, Theodorus A.M. Kaandorp, Hildo J. Lamb, Eric Boersma, Paul Steendijk, Albert de Roos, Ernst E. van der Wall, Martin J. Schalij, Jeroen J. Bax
Journal: Circulation (2006)

Currently, one third of patients treated with cardiac resynchronization therapy (CRT) do not respond. Nonresponse to CRT may be explained by the presence of scar tissue in the posterolateral left ventricular (LV) segments, which may result in ineffective LV pacing and inadequate LV resynchronization. In the present study, the relationship between transmural posterolateral scar tissue and response to CRT was evaluated.Forty consecutive patients with end-stage heart failure (NYHA class III/IV), LV ejection fraction < or =35%, QRS duration >120 ms, left bundle-branch block, and chronic coronary artery disease were included. The localization and transmurality of scar tissue were evaluated with contrast-enhanced MRI. Next, LV dyssynchrony was assessed at baseline and immediately after implantation with tissue Doppler imaging. Clinical parameters, LV volumes, and LV ejection fraction were assessed at baseline and at a 6-month follow-up. Fourteen patients (35%) had a transmural (>50% of LV wall thickness) posterolateral scar. In contrast to patients without posterolateral scar tissue, these patients showed a low response rate (14% versus 81%; P<0.05) and did not show improvement in clinical or echocardiographic parameters. In addition, LV dyssynchrony remained unchanged after CRT implantation (84+/-46 versus 78+/-41 ms; P=NS). Patients without posterolateral scar tissue and severe baseline dyssynchrony (> or =65 ms) showed an excellent response rate of 95% compared with patients with a posterolateral scar and/or absent LV dyssynchrony (11%).CRT does not reduce LV dyssynchrony in patients with transmural scar tissue in the posterolateral LV segments, resulting in clinical and echocardiographic nonresponse to CRT.
Racial Disparities in Cancer Survival Among Randomized Clinical Trials Patients of the Southwest Oncology Group
Authors: Kathy S. Albain, Joseph M. Unger, John J. Crowley, Charles A. Coltman, Dawn L. Hershman
Journal: JNCI Journal of the National Cancer Institute (2009)

Racial disparities in cancer outcomes have been observed in several malignancies. However, it is unclear if survival differences persist after adjusting for clinical, demographic, and treatment variables. Our objective was to determine whether racial disparities in survival exist among patients enrolled in consecutive trials conducted by the Southwest Oncology Group (SWOG).We identified 19 457 adult cancer patients (6676 with breast, 2699 with lung, 1244 with colon, 1429 with ovarian, and 1843 with prostate cancers; 1291 with lymphoma; 2067 with leukemia; and 2208 with multiple myeloma) who were treated on 35 SWOG randomized phase III clinical trials from October 1, 1974, through November 29, 2001. Patients were grouped according to studies of diseases with similar histology and stage. Cox regression was used to evaluate the association between race and overall survival within each disease site grouping, controlling for available prognostic factors plus education and income, which are surrogates for socioeconomic status. Median and ten-year overall survival estimates were derived by the Kaplan-Meier method. All statistical tests were two-sided.Of 19 457 patients registered, 2308 (11.9%, range = 3.9%-21.6%) were African American. After adjustment for prognostic factors, African American race was associated with increased mortality in patients with early-stage premenopausal breast cancer (hazard ratio [HR] for death = 1.41, 95% confidence interval [CI] = 1.10 to 1.82; P = .007), early-stage postmenopausal breast cancer (HR for death = 1.49, 95% CI = 1.28 to 1.73; P < .001), advanced-stage ovarian cancer (HR for death = 1.61, 95% CI = 1.18 to 2.18; P = .002), and advanced-stage prostate cancer (HR for death = 1.21, 95% CI = 1.08 to 1.37; P = .001). No statistically significant association between race and survival for lung cancer, colon cancer, lymphoma, leukemia, or myeloma was observed. Additional adjustments for socioeconomic status did not substantially change these observations. Ten-year (and median) overall survival rates for African American vs all other patients were 68% (not reached) vs 77% (not reached), respectively, for early-stage, premenopausal breast cancer; 52% (10.2 years) vs 62% (13.5 years) for early-stage, postmenopausal breast cancer; 13% (1.3 years) vs 17% (2.3 years) for advanced ovarian cancer; and 6% (2.2 years) vs 9% (2.7 years) for advanced prostate cancer.African American patients with sex-specific cancers had worse survival than white patients, despite enrollment on phase III SWOG trials with uniform stage, treatment, and follow-up.
Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study
Authors: Kay-Tee Khaw, Nicholas Wareham, Sheila Bingham, Ailsa Welch, Robert Luben, Nicholas Day
Journal: PLoS Medicine (2008)

There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community.We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45-79 y with no known cardiovascular disease or cancer at baseline survey in 1993-1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1-14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass-, and social class-adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21-1.60), 1.95 (1.70--2.25), 2.52 (2.13-3.00), and 4.04 (2.95-5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age.Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.
Causes of Early Stent Thrombosis in Patients Presenting With Acute Coronary Syndrome
Authors: Masataka Nakano, Kazuyuki Yahagi, Fumiyuki Otsuka, Kenichi Sakakura, Aloke V. Finn, Robert Kutys, Elena Ladich, David R. Fowler, Michael Joner, Renu Virmani
Journal: Journal of the American College of Cardiology (2014)
Helper T-Cell Responses and Clinical Activity of a Melanoma Vaccine With Multiple Peptides From MAGE and Melanocytic Differentiation Antigens
Authors: Craig L. Slingluff, Gina R. Petroni, Walter Olson, Andrea Czarkowski, William W. Grosh, Mark Smolkin, Kimberly A. Chianese-Bullock, Patrice Y. Neese, Donna H. Deacon, Carmel Nail, Priscilla Merrill, Robyn Fink, James W. Patterson, Patrice K. Rehm
Journal: Journal of Clinical Oncology (2008)

A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel melanoma vaccine comprising six melanoma-associated peptides defined as antigenic targets for melanoma-reactive helper T cells. Source proteins for these peptides include MAGE proteins, MART-1/MelanA, gp100, and tyrosinase.Thirty-nine patients with stage IIIB to IV melanoma were vaccinated with this six-peptide mixture weekly at three dose levels, with a preceding phase I dose escalation and subsequent random assignment among the dose levels. Helper T-lymphocyte responses were assessed by in vitro proliferation assay and delayed-type hypersensitivity skin testing. Patients with measurable disease were evaluated for objective clinical response by Response Evaluation Criteria in Solid Tumors.Vaccination with the helper peptide vaccine was well tolerated. Proliferation assays revealed induction of T-cell responses to the melanoma helper peptides in 81% of patients. Among 17 patients with measurable disease, objective clinical responses were observed in two patients (12%), with response durations of 1 and 3.9+ years. Durable stable disease was observed in two additional patients for periods of 1.8 and 4.6+ years.Results of this study support the safety and immunogenicity of a vaccine comprised of six melanoma helper peptides. There is also early evidence of clinical activity.
Re-activation of bovine tuberculosis in a patient treated with infliximab
Authors: M. V. Larsen, I. J. Sørensen, V. Ø. Thomsen, P. Ravn
Journal: European Respiratory Journal (2008)

Treatment with tumour necrosis factor-α inhibitors increases the risk of tuberculosis (TB). Screening for latent TB infection (LTBI) and prophylactic treatment has become mandatory. A 79-yr-old female with a history of severe erosive sero-positive rheumatoid arthritis was screened for LTBI before initiation of treatment with infliximab. The tuberculin skin test (TST) was negative, chest radiography was normal and she had no known risk factors for TB. After 4 months of treatment with infliximab, the patient developed ascites caused by Mycobacterium bovis . The TST was repeatedly negative. QuantiFERON®-TB (QFT) testing performed during screening and immunosuppressive treatment was indeterminate, whereas the QFT test performed at the time of ascites puncture was positive. The patient history revealed previous work at a dairy, with probable exposure to unpasteurised milk from M. bovis -infected cattle. Re-activation of bovine tuberculosis is a risk in people with recent or previous exposure to unpasteurised dairy products. The QuantiFERON®-TB test has the potential to detect Mycobacterium bovis infection. Indeterminate test results reflect either anergy, due to poor immunity, or technical problems and should be cautiously interpreted and as a minimum be repeated. Studies are ongoing to determine the role of QuantiFERON®-TB testing in the screening for latent tuberculosis infection.
Paradoxical Cellular Ca <sup>2+</sup> Signaling in Severe but Compensated Canine Left Ventricular Hypertrophy
Authors: Long-Sheng Song, YeQing Pi, Song-Jung Kim, Atsuko Yatani, Silvia Guatimosim, Raymond K. Kudej, Qingxiu Zhang, Heping Cheng, Luc Hittinger, Bijan Ghaleh, Dorothy E. Vatner, W. Jonathan Lederer, Stephen F. Vatner
Journal: Circulation Research (2005)

In conscious dogs with severe left ventricular (LV) hypertrophy (H) (doubling of LV/body weight), which developed gradually over 1 to 2 years after aortic banding, baseline LV function was well compensated. The LV was able to generate twice the LV systolic pressure without an increase in LV end-diastolic pressure, or decrease in LV dP/dt or LV wall thickening. However, LV myocytes isolated from LVH dogs exhibited impaired contraction at baseline and in response to Ca2+. There was no change in L-type Ca2+ channel current (ICa) density but the ability of ICa to trigger Ca2+ release from the sarcoplasmic reticulum (SR) was reduced. Immunoblot analysis revealed a 68% decrease in SERCA2a, and a 35% decrease in the number of ryanodine receptors (RyR2), with no changes in protein level of calsequestrin, Na+/Ca2+ exchanger or phospholamban (PLB), but with both RyR2 and PLB hyperphosphorylated. Spontaneous Ca2+ sparks in LVH cells were found to have prolonged duration but similar intensities despite the reduced SR Ca2+ load. A higher Ca2+ spark rate was observed in LVH cells, but this is inconsistent with the reduced SR Ca2+ content. However, Ca2+ waves were found to be less frequent, slower and were more likely to be aborted in Ca2+-challenged LVH cells. These paradoxical observations could be accounted for by a nonuniform SR Ca2+ distribution, RyR2 hyperphosphorylation in the presence of decreased global SR Ca2+ load. We conclude that severe LVH with compensation masks cellular and subcellular Ca2+ defects that remain likely contributors to the limited contractile reserve of LVH.