tbuckley/cabot-search huggingface dataset:
Risk Factors Associated With Suicide in Current and Former US Military Personnel
Authors: Cynthia A. LeardMann, Teresa M. Powell, Tyler C. Smith, Michael R. Bell, Besa Smith, Edward J. Boyko, Tomoko I. Hooper, Gary D. Gackstetter, Mark Ghamsary, Charles W. Hoge
Journal: JAMA (2013)

<h3>Importance</h3> Beginning in 2005, the incidence of suicide deaths in the US military began to sharply increase. Unique stressors, such as combat deployments, have been assumed to underlie the increasing incidence. Previous military suicide studies, however, have relied on case series and cross-sectional investigations and have not linked data during service with postservice periods. <h3>Objective</h3> To prospectively identify and quantify risk factors associated with suicide in current and former US military personnel including demographic, military, mental health, behavioral, and deployment characteristics. <h3>Design, Setting, and Participants</h3> Prospective longitudinal study with accrual and assessment of participants in 2001, 2004, and 2007. Questionnaire data were linked with the National Death Index and the Department of Defense Medical Mortality Registry through December 31, 2008. Participants were current and former US military personnel from all service branches, including active and Reserve/National Guard, who were included in the Millennium Cohort Study (N = 151 560). <h3>Main Outcomes and Measures</h3> Death by suicide captured by the National Death Index and the Department of Defense Medical Mortality Registry. <h3>Results</h3> Through the end of 2008, findings were 83 suicides in 707 493 person-years of follow-up (11.73/100 000 person-years [95% CI, 9.21-14.26]). In Cox models adjusted for age and sex, factors significantly associated with increased risk of suicide included male sex, depression, manic-depressive disorder, heavy or binge drinking, and alcohol-related problems. None of the deployment-related factors (combat experience, cumulative days deployed, or number of deployments) were associated with increased suicide risk in any of the models. In multivariable Cox models, individuals with increased risk for suicide were men (hazard ratio [HR], 2.14; 95% CI, 1.17-3.92;<i>P</i>= .01; attributable risk [AR], 3.5 cases/10 000 persons), and those with depression (HR, 1.96; 95% CI, 1.05-3.64;<i>P </i>= .03; AR, 6.9/10 000 persons), manic-depressive disorder (HR, 4.35; 95% CI, 1.56-12.09;<i>P =</i> .005; AR, 35.6/10 000 persons), or alcohol-related problems (HR, 2.56; 95% CI, 1.56-4.18;<i>P </i>&lt;.001; AR, 7.7/10 000 persons). A nested, matched case-control analysis using 20:1 control participants per case confirmed these findings. <h3>Conclusions and Relevance</h3> In this sample of current and former military personnel observed July 1, 2001-December 31, 2008, suicide risk was independently associated with male sex and mental disorders but not with military-specific variables. These findings may inform approaches to mitigating suicide risk in this population.
Functions, structure, and read-through alternative splicing of feline APOBEC3 genes
Authors: Carsten Münk, Thomas Beck, Jörg Zielonka, Agnes Hotz-Wagenblatt, Sarah Chareza, Marion Battenberg, Jens Thielebein, Klaus Cichutek, Ignacio G Bravo, Stephen J O'Brien, Martin Lochelt, Naoya Yuhki
Journal: Genome biology (2008)

Abstract Background Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene. Results Here we identified and characterized several A3 genes in the genome of domestic cat ( Felis catus ) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three very similar A3C genes (a-c), probably generated after two consecutive gene duplications. In addition to these four one-domain A3 proteins, a fifth A3, designated A3CH, is expressed by read-through alternative splicing. Specific feline A3 proteins selectively inactivated only defined genera of feline retroviruses: Bet-deficient feline foamy virus was mainly inactivated by feA3Ca, feA3Cb, and feA3Cc, while feA3H and feA3CH were only weakly active. The infectivity of Vif-deficient feline immunodeficiency virus and feline leukemia virus was reduced only by feA3H and feA3CH, but not by any of the feA3Cs. Within Felidae, A3C sequences show significant adaptive selection, but unexpectedly, the A3H sequences present more sites that are under purifying selection. Conclusion Our data support a complex evolutionary history of expansion, divergence, selection and individual extinction of antiviral A3 genes that parallels the early evolution of Placentalia, becoming more intricate in taxa in which the arms race between host and retroviruses is harsher.
Arterial and portal blood supply in cirrhosis: a functional evaluation
Authors: P.-M. Huet, A. Du Reau, D. Marleau
Journal: Gut (1979)

The uptake of <sup>125</sup>I albumin microaggregates (U-<sup>125</sup>I-AMA) from portal blood, during a single passage through the hepatic reticuloendothelial system, has been found to be generally decreased in cirrhosis. To investigate if a similar phenomenon occurs for the colloid flowing through the hepatic artery, the U-<sup>125</sup>I-AMA was first calculated in normal dogs after injection of a mixture of <sup>51</sup>Cr red blood cells (<sup>51</sup>Cr-RBC) and <sup>125</sup>I-AMA into the hepatic artery by comparing hepatic indicator dilution curves (IDC) obtained with both indicators. In nine dogs, the U-<sup>125</sup>I-AMA from hepatic artery blood was generally over 90%, as previously reported for the same colloid flowing through the portal vein in another group of normal dogs. This approach was then applied in nine patients with alcoholic cirrhosis who underwent combined umbilicoportal vein, hepatic vein, and hepatic artery catheterisation because of severe portal hypertension. Hepatic indicator dilution curves were obtained in the nine patients after injection of a mixture of <sup>51</sup>Cr-RBC and <sup>125</sup>I-AMA into the portal vein and the hepatic artery. The U-<sup>125</sup>I-AMA from portal and hepatic artery blood was measured by comparing <sup>51</sup>Cr-RBC and <sup>125</sup>I-AMA hepatic IDC. U-<sup>125</sup>I-AMA varied between 5·2 and 90·5% after portal vein injection and between 13·7 and 90·1% after hepatic artery injection; not difference was found between paired values. In all patients the extraction of indocyanine green (E-ICG) was calculated during a continuous infusion and significant correlations were found between E-ICG and U-<sup>125</sup>I-AMA from portal blood (<i>r</i>=0·931; p &lt;0·001) or from hepatic artery blood (<i>r</i>=0·861; p &lt;0·005). The decreased uptakes can be related to intrahepatic shunts or sinusoidal changes responsible for ineffective phagocytosis and restricted access of dye to parenchymal cells. These data indicate that in cirrhosis the hepatic artery and portal vein blood is cleared of colloid and ICG in a similar fashion and suggest nearly identical blood supply to the regenerative nodules by the hepatic artery and portal vein. Thus U-<sup>125</sup>I-AMA from hepatic artery or portal vein blood, as well as the E-ICG, may be used to estimate the functional hepatic blood supply in cirrhosis; this may prove to be useful in the prognosis of patients before portacaval shunts.
Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study
Authors: H. A Capell, R. Madhok, D. R Porter, R. A L Munro, I. B McInnes, J. A Hunter, M. Steven, A. Zoma, E. Morrison, M. Sambrook, F. Wui Poon, R. Hampson, F. McDonald, A. Tierney, N. Henderson, I. Ford
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. <b>Aim:</b> To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP. <b>Methods:</b> A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) ⩾2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS. <b>Results:</b> At 6 months, 191 (28%) patients had a DAS &lt;2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy. <b>Conclusions:</b> In this "true-to-life" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.
Screening for amyloid in subcutaneous fat tissue of Egyptian patients with rheumatoid arthritis: clinical and laboratory characteristics
Authors: T.M. El Mansoury, Bouke Hazenberg, S. A. El Badawy, A.H. Ahmed, J. Bijzet, Pieter Limburg, M.H. Van Rijswijk
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To screen for amyloid and to assess associated clinical and laboratory characteristics in Egyptian patients with rheumatoid arthritis (RA). Methods: Abdominal subcutaneous fat aspirates were consecutively collected from 112 patients (103 women, nine men) having RA for five years or more. To detect amyloid, fat smears were stained with Congo red and the concentration of amyloid A protein in fat tissue was measured. Clinical, radiological, and laboratory characteristics of the patients were assessed. Results: Amyloid was detected in eight (7%) of the fat smears stained with Congo red. Compared with the Congo red stain, the sensitivity for detecting amyloid by measurement of amyloid A protein in fat tissue was 75% and the specificity was 100%. The amount of amyloid found was small for both methods. The median disease duration of the eight amyloid patients was significantly longer (17 years) than that of the non-amyloid patients (10 years). Bronchopulmonary disease and constipation were more common, whereas proteinuria and chronic renal insufficiency were not. The number of swollen joints and the number of red blood cells were significantly lower in the amyloid group. Conclusions: Quantification of amyloid A protein and staining with Congo red are strongly concordant methods of screening for amyloid in fat tissue. The prevalence of amyloid in Egyptian patients with RA is 7%. Proteinuria is not a discriminating feature, whereas long disease duration, constipation, bronchopulmonary symptoms, and a moderate to low number of red blood cells may help to identify the arthritic patients with amyloid.
Antitumor Activity of Targeted and Cytotoxic Agents in Murine Subcutaneous Tumor Models Correlates with Clinical Response
Authors: Harvey Wong, Edna F. Choo, Bruno Alicke, Xiao Ding, Hank La, Erin McNamara, Frank-Peter Theil, Jay Tibbitts, Lori S. Friedman, Cornelis E.C.A. Hop, Stephen E. Gould
Journal: Clinical Cancer Research (2012)

Immunodeficient mice transplanted with subcutaneous tumors (xenograft or allograft) are widely used as a model of preclinical activity for the discovery and development of anticancer drug candidates. Despite their widespread use, there is a widely held view that these models provide minimal predictive value for discerning clinically active versus inactive agents. To improve the predictive nature of these models, we have carried out a retrospective population pharmacokinetic-pharmacodynamic (PK-PD) analysis of relevant xenograft/allograft efficacy data for eight agents (molecularly targeted and cytotoxic) with known clinical outcome.PK-PD modeling was carried out to first characterize the relationship between drug concentration and antitumor activity for each agent in dose-ranging xenograft or allograft experiments. Next, simulations of tumor growth inhibition (TGI) in xenografts/allografts at clinically relevant doses and schedules were carried out by replacing the murine pharmacokinetics, which were used to build the PK-PD model with human pharmacokinetics obtained from literature to account for species differences in pharmacokinetics.A significant correlation (r = 0.91, P = 0.0008) was observed between simulated xenograft/allograft TGI driven by human pharmacokinetics and clinical response but not when TGI observed at maximum tolerated doses in mice was correlated with clinical response (r = 0.36, P = 0.34).On the basis of these analyses, agents that led to greater than 60% TGI in preclinical models, at clinically relevant exposures, are more likely to lead to responses in the clinic. A proposed strategy for the use of murine subcutaneous models for compound selection in anticancer drug discovery is discussed.
Combination DMARD therapy for rheumatoid arthritis: a step closer to the goal.
Authors: J R O'Dell
Journal: Annals of the Rheumatic Diseases (1996)

LeadersCombination DMARD therapy for rheumatoid arthritis: a step closer to the goal "The physician without physiology and chemistry practices a sort of popgun pharmacy, hitting now the malady and again the patient, he himself not knowing which."Sir William Osler Without question the use of combinations of disease modifying antirheumatic drugs (DMARD) to treat rheumatoid arthritis is increasing.A recent survey found that 90% of rheumatologists in the United States use com- binations to treat an estimated 17% of their patients with rheumatoid arthritis.'This compares to use by approximately 50% of rheumatologists in Canada and Australia one decade ago.2Similar figures are not available in Europe, where the use of combinations seems to be less common.The relative frequency of combination therapy used by rheumatologists in the United States suggests their aggressive pursuit of remissions, while the apparent reticence of European rheumatologists may reflects the lack of objective data to support the safety and efficacy of combination DMARD therapy.Rheumatologists in the United States appear to be more aggressive in general, as evidenced by the use of methotrexate as their drug of choice for treatment of rheumatoid arthritis,' while sulphasalazine appears to hold this position in Europe.This trend toward the use of combinations of DMARD to treat patients with rheumatoid arthritis reflects a new standard of care.This new standard is not the use of the combinations themselves but rather the recent
Assessing Health Status and Health Care Utilization in Adolescents with Chronic Kidney Disease
Authors: Arlene C. Gerson, Anne Riley, Barbara A. Fivush, Ngoc Pham, Jeffrey Fiorenza, Judy Robertson, Manju Chandra, Howard Trachtman, Robert Weiss, Susan L. Furth
Journal: Journal of the American Society of Nephrology (2005)

Few validated health status measures have been assessed in children with chronic kidney disease (CKD). The objective was to assess the validity of a generic health status measure, the Child Health and Illness Profile-Adolescent Edition (CHIP-AE), in adolescents with CKD. A case-control study was performed (1) to assess scores on the CHIP-AE in adolescents with CKD compared with two control groups of age-, socioeconomic-, and gender-matched peers and (2) to compare health of patients who had chronic renal insufficiency (CRI), were on dialysis, and were posttransplantation. Seven pediatric nephrology centers recruited 113 patients (mean age, 14 yr; 39 CRI, 21 dialysis, 53 posttransplantation). Compared with 226 control subjects, patients with CKD had lower overall satisfaction with health and more restriction in activity. Positively, patients with CKD had more family involvement, better home safety and health practices, and better social problem-solving skills and were less likely to participate in risky social behaviors or socialize with peers who engaged in risky behavior. Patients who received dialysis were less physically active and experienced more physical discomfort and limitations in activities than did transplant or CRI patients. It is concluded that patients with CKD have poorer functional health status than age-matched peers. Among CKD patients, dialysis patients have the poorest functional health status. These results suggest that the CHIP-AE can be used to measure functional health status in adolescent patients with CKD.
Efficacy of topical isotretinoin 0.05% gel in acne vulgaris: Results of a multicenter, double-blind investigation
Authors: Dan K. Chalker, Jack L. Lesher, J.Graham Smith, Harry C. Klauda, Peter E. Pochi, Wendy S. Jacoby, Donna M. Yonkosky, John J. Voorhees, Charles N. Ellis, Stella Matsuda-John, Alan R. Shalita, Edgar B. Smith, Sharon S. Raimer, John M. Knox, Irwin I. Kantor
Journal: Journal of the American Academy of Dermatology (1987)
The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity
Authors: Zaida G Ramirez-Ortiz, William F Pendergraft, Amit Prasad, Michael H Byrne, Tal Iram, Christopher J Blanchette, Andrew D Luster, Nir Hacohen, Joseph El Khoury, Terry K Means
Journal: Nature Immunology (2013)
Serum C3 Is a Stronger Inflammatory Marker of Insulin Resistance Than C-Reactive Protein, Leukocyte Count, and Erythrocyte Sedimentation Rate
Authors: Antonio Muscari, Serafina Antonelli, Giampaolo Bianchi, Giulia Cavrini, Susanna Dapporto, Amedeo Ligabue, Cosimo Ludovico, Donatella Magalotti, Guido Poggiopollini, Marco Zoli
Journal: Diabetes Care (2007)

This study was performed to ascertain the relative relevance of some inflammatory markers in insulin resistance.Four inflammatory markers (leukocyte count, erythrocyte sedimentation rate [ESR], high-sensitivity C-reactive protein [CRP], and C3 complement) were assessed as possible determinants of the homeostasis model assessment (HOMA) index, together with the five elements of the metabolic syndrome (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III] definition), total cholesterol, physical activity, and four indicators of adiposity (BMI, waist circumference, percent body fat, and hepatic steatosis) in an unselected population of 990 subjects aged 65-91 years (the Pianoro Study).In univariable analysis, C3, CRP, and leukocyte count, but not ESR, were significantly correlated with HOMA index. In multivariable analysis, C3 remained associated with insulin resistance with the highest partial R(2) value (0.049), independently of all other covariates. The other most significant (P < 0.0001) determinants of HOMA index were total cholesterol (inverse association, R(2) = 0.026), waist circumference (R(2) = 0.023), triglycerides (R(2) = 0.022), and hepatic steatosis (R(2) = 0.021) (R(2) = 0.450 for the whole model). The adjusted relative risks of having the metabolic syndrome for the subjects with inflammatory markers in the high tertile, with respect to those with lower values, were (prevalence ratio [95% CI]): 1.77 (1.41-2.22) for C3, 1.38 (1.12-1.70) for leukocyte count, 1.17 (0.94-1.46) for CRP, and 1.13 (0.91-1.40) for ESR.Of the four inflammatory markers simultaneously assessed in our elderly population, only C3 was strongly associated with insulin resistance, independently of the components of the metabolic syndrome and the main indexes of abdominal and general obesity.
Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis
Authors: J. Kluwe, N. Wongsiriroj, J. S. Troeger, G.-Y. Gwak, D. H. Dapito, J.-P. Pradere, H. Jiang, M. Siddiqi, R. Piantedosi, S. M. O'Byrne, W. S. Blaner, R. F. Schwabe
Journal: Gut (2011)

<h3>Objective</h3> Hepatic stellate cells (HSCs) contain a number of bioactive metabolites or their precursors including retinoids in their characteristic lipid droplets. The loss of lipid droplets and retinoids is a hallmark of HSC activation, but it remains unclear whether this loss promotes HSC activation, liver fibrogenesis or carcinogenesis. <h3>Design</h3> Spontaneous and experimental fibrogenesis as well as a diethylnitrosamine-induced hepatocarcinogenesis were investigated in lecithin-retinol acyltransferase (LRAT)-deficient mice which lack retinoid-containing lipids droplets in their HSCs. <h3>Results</h3> Following HSC activation, LRAT expression was rapidly lost, emphasising its importance in lipid droplet biology in HSCs. Surprisingly, there was no difference in fibrosis induced by bile duct ligation (BDL) or by eight injections of carbon tetrachloride (CCl<sub>4</sub>) between wild-type and LRAT-deficient mice. To exclude the possibility that the effects on fibrogenesis were missed due to the rapid downregulation of LRAT following HSC activation, acute as well as spontaneous liver fibrosis was investigated. However, there was no increased fibrosis in 3-, 8- and 12-month-old LRAT-deficient mice and in LRAT-deficient mice after a single injection of CCl<sub>4</sub> compared with wild-type mice. To determine whether the absence of retinoids in HSCs affects hepatocarcinogenesis, wild-type and LRAT-deficient mice were injected with diethylnitrosamine. LRAT deficiency decreased diethylnitrosamine-induced injury and tumour load and increased the expression of the retinoic acid responsive genes Cyp26a1, RARb and p21, suggesting that the lower tumour load of LRAT-deficient mice was a result of increased retinoid signalling and subsequent p21-mediated inhibition of proliferation. <h3>Conclusions</h3> The absence of retinoid-containing HSC lipid droplets does not promote HSC activation but reduces hepatocarcinogenesis.