tbuckley/cabot-search huggingface dataset:
Improving the Accuracy of Demographic and Molecular Clock Model Comparison While Accommodating Phylogenetic Uncertainty
Authors: Guy Baele, Philippe Lemey, Trevor Bedford, Andrew Rambaut, Marc A. Suchard, Alexander V. Alekseyenko
Journal: Molecular Biology and Evolution (2012)

Recent developments in marginal likelihood estimation for model selection in the field of Bayesian phylogenetics and molecular evolution have emphasized the poor performance of the harmonic mean estimator (HME). Although these studies have shown the merits of new approaches applied to standard normally distributed examples and small real-world data sets, not much is currently known concerning the performance and computational issues of these methods when fitting complex evolutionary and population genetic models to empirical real-world data sets. Further, these approaches have not yet seen widespread application in the field due to the lack of implementations of these computationally demanding techniques in commonly used phylogenetic packages. We here investigate the performance of some of these new marginal likelihood estimators, specifically, path sampling (PS) and stepping-stone (SS) sampling for comparing models of demographic change and relaxed molecular clocks, using synthetic data and real-world examples for which unexpected inferences were made using the HME. Given the drastically increased computational demands of PS and SS sampling, we also investigate a posterior simulation-based analogue of Akaike's information criterion (AIC) through Markov chain Monte Carlo (MCMC), a model comparison approach that shares with the HME the appealing feature of having a low computational overhead over the original MCMC analysis. We confirm that the HME systematically overestimates the marginal likelihood and fails to yield reliable model classification and show that the AICM performs better and may be a useful initial evaluation of model choice but that it is also, to a lesser degree, unreliable. We show that PS and SS sampling substantially outperform these estimators and adjust the conclusions made concerning previous analyses for the three real-world data sets that we reanalyzed. The methods used in this article are now available in BEAST, a powerful user-friendly software package to perform Bayesian evolutionary analyses.
Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer
Authors: Nancy L. Keating, A. James O'Malley, Matthew R. Smith
Journal: Journal of Clinical Oncology (2006)

Androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist is associated with increased fat mass and insulin resistance in men with prostate cancer, but the risk of obesity-related disease during treatment has not been well studied. We assessed whether androgen deprivation therapy is associated with an increased incidence of diabetes and cardiovascular disease.Observational study of a population-based cohort of 73,196 fee-for-service Medicare enrollees age 66 years or older who were diagnosed with locoregional prostate cancer during 1992 to 1999 and observed through 2001. We used Cox proportional hazards models to assess whether treatment with GnRH agonists or orchiectomy was associated with diabetes, coronary heart disease, myocardial infarction, and sudden cardiac death.More than one third of men received a GnRH agonist during follow-up. GnRH agonist use was associated with increased risk of incident diabetes (adjusted hazard ratio [HR], 1.44; P < .001), coronary heart disease (adjusted HR, 1.16; P < .001), myocardial infarction (adjusted HR, 1.11; P = .03), and sudden cardiac death (adjusted HR, 1.16; P = .004). Men treated with orchiectomy were more likely to develop diabetes (adjusted HR, 1.34; P < .001) but not coronary heart disease, myocardial infarction, or sudden cardiac death (all P > .20).GnRH agonist treatment for men with locoregional prostate cancer may be associated with an increased risk of incident diabetes and cardiovascular disease. The benefits of GnRH agonist treatment should be weighed against these potential risks. Additional research is needed to identify populations of men at highest risk of treatment-related complications and to develop strategies to prevent treatment-related diabetes and cardiovascular disease.
Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion
Authors: José Milei, Pedro Forcada, César G. Fraga, Daniel R. Grana, Gabriele Iannelli, Massimo Chiariello, Isabella Tritto, Giuseppe Ambrosio
Journal: Cardiovascular Research (2006)

In animal models, formation of oxidants during postischemic reperfusion may exert deleterious effects ("oxidative stress"). Cardioplegic arrest/reperfusion during cardiac surgery might similarly induce oxidative stress. However, the phenomenon has not been precisely characterized in patients, and therefore the role of antioxidant therapy at cardiac surgery is a matter of debate. Thus, we wanted to ascertain whether the relationship between oxidant formation and development of myocardial injury also translates to the situation of patients subjected to cardioplegic arrest.In 24 patients undergoing coronary artery bypass, trans-cardiac blood samples and myocardial biopsies were taken before cardioplegic arrest and again following reperfusion.Cardiac glutathione release (marker of oxidant production) was negligible at baseline (0.02+/-0.04 micromol/L), but it increased 15 min into reperfusion (1.10+/-0.40 micromol/L; p<0.05); concomitantly, myocardial concentration of the antioxidant ubiquinol decreased from 144.5+/-52.0 to 97.6+/-82.0 nmol/g (p<0.05). Although these changes document cardiac exposure to oxidants, they were not accompanied by evidence of injury. Neither coronary sinus blood nor cardiac biopsies showed increased lipid peroxide concentrations. Furthermore, electron microscopy showed no major ultrastructural alterations. Finally, full recovery of left ventricular systolic and diastolic function was observed.Careful investigation reveals that while oxidant production does occur during cardiac surgery in patients with chronic ischemic heart disease, cardiac oxidative stress may not progress through membrane damage and irreversible injury.
Asthma and Airway Hyperresponsiveness
Authors: R H Ingram
Journal: Annual Review of Medicine (1991)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Conservation of Distantly Related Membrane Proteins: Photosynthetic Reaction Centers Share a Common Structural Core
Authors: Sumedha Sadekar, Jason Raymond, Robert E. Blankenship
Journal: Molecular Biology and Evolution (2006)

Photosynthesis was established on Earth more than 3 billion years ago. All available evidences suggest that the earliest photosynthetic organisms were anoxygenic and that oxygen-evolving photosynthesis is a more recent development. The reaction center complexes that form the heart of the energy storage process are integral membrane pigment proteins that span the membrane in vectorial fashion to carry out electron transfer. The origin and extent of distribution of these proteins has been perplexing from a phylogenetic point of view mostly because of extreme sequence divergence. A series of integral membrane proteins of known structure and varying degrees of sequence identity have been compared using combinatorial extension–Monte Carlo methods. The proteins include photosynthetic reaction centers from proteobacteria and cyanobacterial photosystems I and II, as well as cytochrome oxidase, bacteriorhodopsin, and cytochrome b. The reaction center complexes show a remarkable conservation of the core structure of 5 transmembrane helices, strongly implying common ancestry, even though the residual sequence identity is less than 10%, whereas the other proteins have structures that are unrelated. A relationship of sequence with structure was derived from the reaction center structures; with characteristic decay length of 1.6 Å. Phylogenetic trees derived from the structural alignments give insights into the earliest photosynthetic reaction center, strongly suggesting that it was a homodimeric complex that did not evolve oxygen.
Severe cytomegalovirus pneumonitis in HIV infected patients with higher than average CD4 counts.
Authors: S B Squire, M C Lipman, E K Bagdades, P M Mulvenna, J E Grundy, P D Griffiths, M A Johnson
Journal: Thorax (1992)

Cytomegalovirus may replicate within the lungs both of recipients of transplants and of patients infected with the human immunodeficiency virus (HIV). A hypothesis formulated by this group was that a host damaging immune response might be provoked by cytomegalovirus infection and cause a severe pneumonitis in recipients of allogeneic transplants, whereas the progressive impairment of cellular immunity in patients with HIV disease would preclude a damaging immune response in the lungs, and thus protect these patients from severe cytomegalovirus pneumonitis. This study set out to discover whether severe cytomegalovirus pneumonitis arises in HIV infected patients.Data were prospectively collected on severity of pneumonitis and infectious agents identified in consecutive respiratory episodes in HIV infected patients undergoing diagnostic bronchoalveolar lavage during 20 months.Eighty five episodes of pneumonitis occurred in 68 patients. Cytomegalovirus was identified as the only infectious agent in nine episodes (nine patients). Seven of the episodes were mild; all these patients had CD4 counts below 0.1 x 10(9)/1. The remaining two episodes were severe and ventilatory support was required. In both cases the CD4 counts were above 0.2 x 10(9)/1 and HIV infection appeared to have been acquired shortly before presentation.Although rare, severe cytomegalovirus pneumonitis may occur in HIV infected patients. Both patients with severe pneumonitis in this series had relatively well preserved immune function. These findings support the hypothesis that severe cytomegalovirus pneumonitis is an immunopathological condition.
A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus.
Authors: I Khalil, L d'Auriol, M Gobet, L Morin, V Lepage, I Deschamps, M S Park, L Degos, F Galibert, J Hors
Journal: Journal of Clinical Investigation (1990)

Family and population studies indicate that predisposition to insulin-dependent (type I) diabetes mellitus (IDDM) is polygenic. It has been shown that the absence of the aspartic acid in position 57 (Asp57) of the DQ beta chain is positively correlated to IDDM. However, Asp57-negative haplotypes do not always confer susceptibility and conversely, some Asp57-positive haplotypes seem to be disease associated. It has been suggested that other HLA class II sequences, probably belonging to the HLA DQA1 gene, confer susceptibility to IDDM. This report, based on extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes, reinforces the importance of the Asp57-negative DQ beta chain, but also introduces the possibility that a DQ alpha chain bearing an arginine in position 52 (Arg52) confers susceptibility to IDDM. A molecular model of susceptibility to IDDM is proposed. This model strongly suggests that the disease susceptibility correlates quantitatively with the expression at the cell surface of a heterodimer, composed of a DQ alpha-chain bearing an Arg52 and a DQ beta chain lacking an Asp57. In view of the respective positions of the two residues and their charge, we might anticipate that both residues DQ beta Asp57 and DQ alpha Arg52 are critical for modulation of susceptibility, presumably via viral-antigenic peptide and/or autoantigen presentation.
THE INFLUENCE OF BLOOD GLUCOSE ON THE RENAL CLEARANCE OF PHOSPHATE12
Authors: E. R. Huffman, C. J. Hlad, N. E. Whipple, H. Elrick
Journal: Journal of Clinical Investigation (1958)

Many factors have been shown to influence the level of inorganic phosphorus 8 in the blood (1-5).Among these are glucose and insulin, each of which consistently decreases plasma phosphate (1, 3).Since it has been shown that phosphate excre- tion is dependent upon plasma phosphate (5), one would expect insulin or glucose to alter phos- phate excretion in a predictable manner.How- ever, reports on this point have been very con- flicting; decreases (6), increases (1, 7) and no change (8, 9) in phosphate excretion following glucose or insulin have been described.During the course of studies on the renal ef- fects of glucagon (10, 11), a consistent relation- ship between blood glucose level and renal phos- phate clearance was observed.The purpose of this paper is to define this relationship and to point out its physiologic implications. METHODSStudies were carried out in 40 hospitalized ambula- tory male patients with no evidence of renal disease.All subjects were studied in the postabsorptive state (14 hour fast).Water was ingested before and during the experiments to assure adequate urine flows.Intra- venous infusion of glucose, insulin,' or buffered phos- phate (pH 7.4) solutions was accomplished by a Bowman constant infusion pump.In two subjects glucose was ad- ministered orally as a 50 per cent solution.In two other subjects tolbutamide (Orinase®, sodium)5 was adminis- tered as a single intravenous injection over a five min- ute period.Standard renal clearance techniques were used with endogenous creatinine clearance as a meas- ure of glomerular filtration rate.Phosphate clearance is 1 Presented at a meeting of the American Federation for Clinical Research, Carmel, Calif., January 30, 1957. 2 Supported in part by a grant from the Upjohn Co., Kalamazoo, Mich.3 Hereafter, inorganic phosphorous is referred to as phosphate.4 Insulin free of glucagon (Lot T-3206) kindly sup- plied by
Joint fluid cytology in Reiter's disease.
Authors: A I Spriggs, M M Boddington, A G Mowat
Journal: Annals of the Rheumatic Diseases (1978)

The diagnostic value of the finding of cytophagocytic macrophages (CPM) in the joint fluid of patients with Reiter's disease has been re-examined. CPM were found in 46% of Reiter's disease fluids and in 45% of other inflammatory knee joint fluids. Higher CPM scores, on a 4-point grading, were commoner in Reiter's disease but the difference was not statistically significant. Further, although the graded polymorphonuclear leucocyte phagocytosis shown by CPM was greater in Reiter's disease this also was not significant. It is concluded that the presence of CPM in joint fluid is of little discriminating value.
Patient and health care providers (HCP) perception of sedation & comfort during acute non-invasive ventilation (NIV)
Authors: April Thompson, Swapna Mandal, H. Nicholas, Craig Davidson
Journal: European Respiratory Journal (2013)

Introduction : Agitation, confusion and poor mask tolerance are main factors contributing to poor adherence and often failure of acute NIV. However, there is limited data in the use of sedation to enhance NIV adherence.   Methods : Patients requiring NIV were included in a 12 month period from January to December 2012. Patient and health care providers (HCP) perceptions surrounding the use of sedation and comfort were measured following cessation of NIV and repeated 6 weeks post discharge.   Results : 42 patients, 57% female (age 68.9±12.9 years) were included. 30% experienced an episode of agitation, confusion or aggressive behaviour. 21% were prescribed but only 11% received sedation during NIV. A higher tolerance throughout, and some perceived benefit during initiation of NIV was observed in patients in the ‘sedated’ group (figure1). 21% died prior to the 6 week follow up. Of the survivors, only 16% completed the post-discharge questionnaire. Prior to discharge, 50% of patients reported that they would accept sedation if offered and 66% perceived that this would improve their adherence.   Conclusion : Sedation may aid NIV tolerance and adherence. Furthermore, it is acceptable to patients. These data highlight the need to consider the use of supplemental sedation during the use of acute NIV.
Impact of Oophorectomy on Cancer Incidence and Mortality in Women With a <i>BRCA1</i> or <i>BRCA2</i> Mutation
Authors: Amy P.M. Finch, Jan Lubinski, Pål Møller, Christian F. Singer, Beth Karlan, Leigha Senter, Barry Rosen, Lovise Maehle, Parviz Ghadirian, Cezary Cybulski, Tomasz Huzarski, Andrea Eisen, William D. Foulkes, Charmaine Kim-Sing, Peter Ainsworth, Nadine Tung, Henry T. Lynch, Susan Neuhausen, Kelly A. Metcalfe, Islay Thompson, Joan Murphy, Ping Sun, Steven A. Narod
Journal: Journal of Clinical Oncology (2014)

The purposes of this study were to estimate the reduction in risk of ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2 mutation after oophorectomy, by age of oophorectomy; to estimate the impact of prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival associated with clinically detected ovarian, occult, and peritoneal cancers diagnosed in the cohort.Women with a BRCA1 or BRCA2 mutation were identified from an international registry; 5,783 women completed a baseline questionnaire and ≥ one follow-up questionnaires. Women were observed until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and all-cause mortality associated with oophorectomy were evaluated using time-dependent survival analyses.After an average follow-up period of 5.6 years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13 to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95% CI, 0.13 to 0.39; P < .001).Preventive oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality.
BRCA1 and BRCA2 mutations as prognostic factors in bilateral breast cancer patients
Authors: J. Rogozińska-Szczepka, B. Utracka-Hutka, E. Grzybowska, B. Mąka, E. Nowicka, A. Smok-Ragankiewicz, H. Zientek, J. Steffen, A. Wojciechowska-Łącka
Journal: Annals of Oncology (2004)
A4.15 Osteoporosis knowledge, self-efficacy, and health beliefs among chinese men and women with HIV
Authors: Evelyn Hsieh, Liana Fraenkel, Elizabeth Bradley, Weibo Xia, Cui Qu, Luo Ling, Karl Insogna, Taisheng Li
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Prior studies demonstrate increased rates of osteoporosis and fracture among patients with HIV. Validated scales exist for measuring osteoporosis-related knowledge, self-efficacy for behavioural change, and health beliefs, but have not yet been applied to HIV-infected populations. Better understanding of these factors can increase the effectiveness of osteoporosis prevention efforts. <h3>Materials and Methods</h3> Subjects were drawn from a multi-center trial in China comparing 3 antiretroviral regimens. Volunteers completed a questionnaire with 6 sections including: 1. Fracture risk assessment, 2. International Physical Activity Questionnaire (IPAQ), 3. Calcium and vitamin D intake scale, 4. Osteoporosis Knowledge Test (OKT), 5. Osteoporosis Self-Efficacy Scale (OSES), and 6. Osteoporosis Health Beliefs Scale (OHBS). Demographic data were obtained from the parent study. <h3>Results</h3> In total 263 subjects participated (200 men, 63 women). Mean age (38.4 ± 9.8 yrs.) and BMI (21.6 ± 2.6 kg/m<sup>2</sup>) were similar for both sexes. Men were more likely to have completed high school (69 v. 23.8%, p = 0.000) and report smoking (49 v. 8.8%, p = 0.000) or alcohol use (26.8 v. 12.3%, p = 0.022) than women. Moderate physical activity level was most common for both sexes (41.8 v. 44.6%, p = 0.931) and mean frequency of consumption of calcium and vitamin D-rich foods was similar in both groups (p = 0.257). OKT calcium and exercise scores were low for both groups, yet OSES calcium and exercise scores reflected moderate confidence regarding ability to adopt behavioural change. Subjects did not perceive personal susceptibility to osteoporosis and felt neutral regarding the seriousness of a diagnosis of osteoporosis. Both men and women recognised benefits of exercise and calcium intake, however men were less likely to perceive barriers to exercise and calcium intake compared with women. Both sexes reported moderate overall health motivation. Multiple regression analysis showed that higher intake of calcium and vitamin D rich foods was associated with higher OKT calcium score (β = 0.29, 95% CI 0.01 to 0.58, p = 0.043) and OSES calcium score (β = 0.07, 95% CI 0.03 to 0.11, p = 0.001), whereas higher physical activity level correlated with lower education (β = 0.45, 95% CI 0.25 to 0.81, p = 0.008). <h3>Conclusions</h3> Knowledge regarding osteoporosis is low among Chinese men and women with HIV, and women perceive more barriers to behavioural change than men. Calcium and vitamin D intake and physical activity levels have different predictors. Understanding these associations may aid in the development of targeted behavioural interventions for this vulnerable group.
Control of hepatitis B infection. The role of surveillance and an isolation hemodialysis center
Authors: G. R. Najem
Journal: JAMA (1981)

A 3 1/4-year study assessed intervention approaches for hemodialysis-associated hepatitis. A 12-month retrospective study was followed by one year of prospective surveillance (during which attention to hygienic techniques was encouraged) and then by a 15-month period during which antigen-positive cases were transferred from study centers to an isolation hemodialysis center (IHL). The incidence of hepatitis B infection (HBI) fell 35.9% in study centers during surveillance; this was followed by a 50.0% drop during the IHC phase. The total 67.9% drop during the entire study period was statistically highly significant; the IHC contributed significantly more to the total drop than did surveillance alone. At comparison units, HBI increased 97.9% during the same period. This study indicates that HBI incidence can be markedly reduced by a combination of surveillance and assignment of antigen-positive patients to a separate dialysis unit.
Intense isolated expression with preS1 (large protein) antibodies in the liver graft associated with severe acute hepatitis B virus reactivation
Authors: Jean-Charles Duclos-Vallée, Jean-François Emile, Kinan Rifai, Anne-Marie Roque-Afonso, Cyrille Feray, Marie-Anne Petit, Didier Samuel
Journal: Journal of Hepatology (2001)

A 64-year-old man underwent liver transplantation in November 1999 for hepatocellular carcinoma and hepatitis B virus (HBV) cirrhosis. In July 2000, 3 weeks after a third course of an adjuvant chemotherapy, liver biopsy was performed in urgency because of a sudden increase in transaminase activity. The HBV serological status of the patient was HBs Ag negative and anti-HBs positive consecutive of passive immunotherapy. On liver biopsy, a strong immunolabeling with monoclonal antibody F35.25 directed against the preS1 region (21–47) of HBV large protein was observed, while immunolabeling with polyclonal and monoclonal anti-HBc and anti-HBs antibodies was negative (see figures). This negative immunolabeling could be explained by (1) one or several mutations of the core gene, which we are currently studying and (2) the fact that the patient was receiving immunoprophylaxis with hepatitis B immunoglobulin, which may inhibit the detection of AgHBs.